key: cord- -j q l authors: khalafalla, abdelmalik i. title: emerging infectious diseases in camelids date: - - journal: emerging and re-emerging infectious diseases of livestock doi: . / - - - - _ sha: doc_id: cord_uid: j q l growing interest in camelids presents a unique challenge to scientists and veterinarians engaged in diagnosing infectious diseases of this species. it is estimated that % of fatalities in old world camels (owc, i.e., camelus dromedarius and c. bactrianus) and % in new world camelids/south american camelids (nwc/sac, i.e., the domestic alpaca (vicugna pacos) and llama (lama glama)) are caused by infectious diseases. factors that contribute to disease emergence in camelids involve climate change and increased demand for camel products resulting in the intensification of production and expanding camel contacts with other animal species and humans. in this chapter, the most important emerging diseases of camelids are described and discussed. the most notable emerging viral infections in owc include camelpox, rift valley fever (rvf), peste des petits ruminants (ppr), and middle east respiratory syndrome coronavirus (mers-cov) infection. brucellosis, johne’s disease (jd), and dermatophilosis are the emerging bacterial diseases in owc. emerging diseases of nwc include infections with bovine viral diarrhea virus (bvdv), bluetongue (bt), and coronavirus. parasitic emerging infections in nwcs include the small liver fluke (dicrocoelium dendriticum) and meningeal worm (parelaphostrongylus tenuis). it is estimated that % of fatalities in old world camels (owc, i.e., camelus dromedarius and c. bactrianus) and % in new world camelids/south american camelids (nwc/sac, i.e., the domestic alpaca (vicugna pacos) and llama (lama glama)) are caused by infectious diseases (wernery and kaaden ) . in the past, camels were used mainly for transportation beside their role as the main source of milk and meat for pastoralists. dromedary camel in sub-saharan africa was traditionally known to be reared in the arid and semiarid lands. due to aridity and desertification, they obliged to move to the higher rainfall areas side by side with other domestic livestock and wildlife. this change resulted in exposure of camels to diseases that were uncommon in their natural habitat such as dermatophilosis, tick paralysis, trypanosomosis, and brucellosis. the situation in niger, chad, and sudan is an example where diseases like contagious ecthyma, trypanosomosis, and tick paralysis have become very serious with increased mortality rates due to the migration of camels south of their well-known camel belt. drought in the sahel and the horn of africa has also brought pastoralists closer to urban centers, and sales of camel milk became their main source of cash income. due to an increased demand of urban populations of many countries, particularly in north africa and the middle east for camel milk, many dairy farms are established in intensive and semiintensive systems. this development may be responsible for making camels more susceptible to certain disease. brucellosis, enterotoxemia, and johne's disease are examples of these diseases. a similar situation could be envisaged for an increased incidence of enterotoxemia in camels when raised in an intensive husbandry system as in the uae (wernery and kaaden ) or syria (khalafalla ai , personnel communication) . changes in animal husbandry related to increasing camel contacts with other animal species, such as equids, may cause disease emergence. examples of newly emerged diseases of camels resulting from sharing premises with equines are glanders , melioidosis (wernery et al. ) , and rhodococcus equi infection . another factor that may contribute to the emergence of camel diseases is the migration into new habitat that never was reached before by camels (faye and vias ) . camelpox is the only camel disease included in the oie's list of reportable diseases. a chapter on camelpox has been recently added to the oie's manual of terrestrial animal diseases, following its endorsement by oie's assembly during the general session of may . a special research interest in camelpox has resulted in numerous publications on different aspects of the disease and the causative virus. this is mainly attributable to the resemblance of the cmlv to small poxvirus (baxby ) . interestingly, the cmlv is recently becoming the subject for studies on antiviral therapies (duraffour et al. ) , cellular ion channel analysis, and apoptosis. camelpox is a highly contagious skin disease and the most frequent infectious viral disease of the camelids that occurs in almost every country in which camel husbandry is practiced (fig. . ). outbreaks have been reported in asia (bahrain, iran, iraq, oman, saudi arabia, the uae, yemen, syria, afghanistan, southern parts of russia and india, and pakistan) and in africa (algeria, egypt, ethiopia, kenya, mauritania, morocco, niger, somalia, and sudan). the disease is endemic in these countries, and a pattern of sporadic outbreaks occurs with a rise in the seasonal incidence usually during the rainy season (oie ) . the disease was recently reported from saudi arabia (yousif ) , india (bhanuprakash et al. ; bera et al. ) , ethiopia (ayelet et al. ) , and iran (mosadeghhesari et al. ). camelpox is caused by the camelpox virus (cmlv), which belongs to the genus orthopoxvirus (opxv) of the subfamily poxvirinae in the family poxviridae. phylogenetic analysis of cmlv revealed that cmlv is most closely related to variola virus (varv), sharing all genes involved in basic replicative functions and the majority of genes involved in other host-related functions (afonso et al. ; gubser and smith ) . the disease is species specific and characterized by localized or generalized pox lesions that vary in severity in correlation with age of affected animals (khalafalla and mohamed ) . pox lesion of various stages may develop, particularly on the face, the neck, and under the tail (fig. . ). other symptoms include fever and lymph node enlargement. abortion rates may reach %, as observed by al zi'abi et al. ( ) in syria. the presumptive diagnosis of camelpox infection can be made based on clinical signs. however, infections of camels in the early clinical stages and in mild cases should be differentiated from contagious ecthyma, which is caused by a parapoxvirus (ppv), papilloma virus infections, and insect bites (khalafalla et al. ; bhanuprakash et al. ) . various laboratory techniques are available for the diagnosis of camelpox including virus isolation, electron microscopy, serology, and polymerase chain reaction (pcr). it has been over years since camelpox was first described in punjab, india, in (wernery and kaaden ) , but the zoonotic nature of the cmlv remained a debate. according to baxby ( ) , cmlv is different from the varv, the causative agent of smallpox, and is incapable of infecting man. kritz in somalia (kritz ) described the first report of a case of human camelpox. the case was a -year-old camel herder who developed lesions resembling those of smallpox in june . from the s until recently, it has been well accepted that cmlv rarely infects humans (duraffour et al. ) . this is probably due to the crossimmunity induced via smallpox vaccination that ended in the late s. it was therefore postulated that human camelpox may become more common as the immunity of the human population wanes (duraffour et al. ) . human population more than three decades after cessation of the smallpox vaccination has lost protection against that deadly virus and all zoonotic infections caused by human and animal opvs as well. the first conclusive evidence of zoonotic cmlv infection in humans, associated with outbreaks in dromedary camels, has been recently reported in india where three human cases of camelpox have been reported (bera et al. ). they were detected in animal handlers during an outbreak of camelpox, and the lesions were confined to the hands and fingers of camel handlers and passed through all the stages of pox lesions until the formation of scabs. these are the first confirmed cases of zoonotic camelpox as infection was diagnosed by conventional pcr and seroconversion. additional four cases of camelpox in humans ( rift valley fever is an acute viral, mosquito-borne disease that affects domestic animals (such as sheep, cattle, and goats) and humans distributed in sub-saharan african countries and the arabian peninsula. camels have been regularly involved in the rvf epidemics in east africa and egypt. however, clinical disease is not seen in adult camels, but abortion occurs and some early deaths have been observed (oie ) . serological evidence of dromedary camel infection with rvf was documented. according to davies et al. ( ) , camel sera collected after an epizootic of rift valley fever in kenya revealed positive sera with high titers of serum neutralizing antibody found in % of camels at one of the seven sampling sites. furthermore, the demonstration of specific igg antibodies in camels (nabeth et al. ) indicates that these animals are naturally infected. the disease emerged in egypt in , in mauritania in (nabeth et al. ) , and in the arabian peninsula in (abdo-salem et al. ). in addition, the disease reappeared in kenya in (bird et al. . it also involved camels beside sheep, goats, and humans, again with abortion as the only clinical symptom. recently, el mamy et al. ( ) have reported confirmatory evidence for a field camel infection with rvf. in september of , an rvf outbreak occurred in northern mauritania involving mass abortions in small ruminants and camels (camelus dromedarius) and at least human clinical cases, including deaths. in camels, serological prevalence was . - . %, and for the first time, clinical signs other than abortions were reported in this species, including hemorrhagic septicemia and severe respiratory distress (fig. . ) . phylogenetic analyses of the genome of isolates from camels suggested a shared ancestor between the mauritania strain and strains from zimbabwe, kenya, south africa, uganda, and other strains linked to the outbreak of rvf in mauritania. peste des petits ruminants (ppr) is a highly contagious disease of sheep and goats which has recently reemerged and is now found widely distributed through large parts of africa, the middle east, and asia. the disease is characterized by severe pyrexia, anorexia, ulcerative necrotic stomatitis, diarrhea due to purulent oculo-nasal discharge, and respiratory distress. the disease is caused by the peste des petits ruminant virus (pprv), which belongs to the morbillivirus genus of the paramyxovirus family of viruses. pprv is a non-segmented negative-strand rna virus closely related to the rinderpest virus of cattle and buffaloes, the measles virus of humans, the distemper virus of dogs and some wild carnivores, and the morbilliviruses of aquatic mammals. to date, genetic characterization of ppr virus strains has allowed them to be categorized into four groups: three from africa and one from asia. this virus has a particular affinity for lymphoid tissues and epithelial tissue of the gastrointestinal (gi) and respiratory tracts, where it produces characteristic lesions. ppr in camelids camels were not reported as possible hosts to ppr until ismail and coauthors (ismail et al. ) in egypt detected the infection through serology in sudanese camels. the first documented outbreak of ppr in camels reported from ethiopia in , consisted of a highly contagious respiratory syndrome with elevated morbidity and low mortality rates (roger et al. (roger et al. , the clinical and epidemiological picture of the previous ppr-suspected or pprconfirmed outbreaks in northeast africa is not similar. at least two forms can be identified: a per acute disease characterized by sudden death, abortion, and diarrhea with a high mortality rate occurred in the region during (gluecks and younan dawo ; khalafalla et al. ) , whereas the early outbreaks ( ) ( ) ( ) ( ) ( ) showed an acute respiratory disease with low mortality rates (roger et al. ) . the presence of more than one form points to involvement of other pathogens as secondary invaders or to the genetic variations of the causative virus. the last hypothesis was verified by detecting lineage iii of pprv from camels in ethiopia in and lineage iv from camels affected by pprv in in sudan (kwiatek et al. ). kwiatek and coworkers ( ) suggested that a virulent lineage iv strain might have been introduced in africa during the s, resulting in outbreaks in both camels and small ruminants. clinically the disease is characterized by sudden death of apparently healthy animals and yellowish and later bloody diarrhea and abortion (fig. . ). death has been always sudden and proceeded with colic and difficulty in respiration. mortality rate ranges between and % and vary in accordance with the area with a mean of . %. more than % of deaths were in pregnant and recently delivered she-camels. middle brucellosis is one of the most important worldwide zoonosis affecting livestock and humans. the disease is regarded as one of the most widespread diseases in the world by the food and agriculture organization of the united nations (fao), the world health organization (who), and the world animal health organization (oie). camels of both species (camelus dromedarius and camelus bactrianus) are highly susceptible to brucellosis caused by b. melitensis and b. abortus. however, too few bacteriological surveys have been conducted to draw conclusions on the relative importance of either species of brucella in the etiology of camel brucellosis in the respective countries (abbas and agab ) . a recent report regarded brucellosis as a regionally emerging zoonotic disease in north africa, the middle east, and india (gwida et al. ) . camels are infected by brucella abortus and b. melitensis, which cause abortion and infertility (wernery and kaaden ) . b. melitensis was isolated from camels in iran, libya, and saudi arabia; b. abortus was isolated in sudan, egypt, and kuwait. serological surveys of camels conducted in many countries indicated that seroprevalence of b abortus ranged from to %. however, recent reports showed a substantial increase in seroprevalence over the past few years (ahmed et al. ) . the increase reached . % in some areas in sudan (omer et al. ) . clinical disease was also reported (musa et al. ; al-majali et al. ) . clinically, brucellosis in camelids induce symptoms similar to those in other livestock species. however, various researchers have noticed that abortion related to brucellosis is less in camels in comparison to other animals. brucella infections in camels may cause stillborn calves, retained placenta, fetal death, mummification, reduced milk yield, delayed service age, and fertility (wernery ) . johne's disease (jd), also known as paratuberculosis, is widespread, chronic, and debilitating disease that affects mainly ruminants and causes severe economic loss. once animals are infected, the disease gradually advances toward its chronic form, which is characterized by granulomatous enteritis, progressive weight loss with diarrhea, and finally death. mycobacterium avium subspecies paratuberculosis (map) causes johne's disease in domestic and wild ruminant and in camelids. a recent study by ghosh and coauthors based on gene typing of map isolates from saudi arabia indicated that all isolates belong to the sheep lineage of strains, suggesting a putative transmission from infected sheep herds (ghosh et al. ). jd affects camels worldwide, causing characteristic clinical illness of severe diarrhea ending in death (manefield and tinson ; wernery and kaaden ) (fig. . ) . the course of disease is often more rapid than that in cattle (higgins ) . reports from saudi arabia described many deaths due to this disease. according to gameel et al. ( ) , nine camels died after displaying fig. . a - year-old camel affected with johne's disease characteristic symptoms. the diagnosis was laboratory confirmed, and according to owners, camels died in the field after showing typical symptoms. the disease continues to be reported as a serious and invariably fatal disease of the arabian camel ). according to several reports, johne's disease is considered an important emerging disease in dromedary camels in the saudi arabia and gulf states. glanders in equids caused by burkholderia mallei recently reappeared in pakistan and brazil in and , respectively, and appeared for the first time in kuwait and bahrain in (wernery ; roberts et al. ) . recently, an outbreak of glanders that killed three dromedaries out of six was diagnosed in bahrain . melioidosis is a potentially fatal disease caused by the gram-negative bacterium burkholderia pseudomallei. during , seven out of camels died from the disease in queensland, australia (bergin and torenbeck ) . since then, at least four incidents of melioidosis-related camel deaths have been diagnosed in the northern areas of the northern territory in australia, and a single case was reported from the uae (wernery et al. ). natural dermatophilus congolensis infection of camels has been reported, for the first time, in kenya, sudan, the uae, and saudi arabia in the mid- s (bornstein , gitao et al. a wernery and ali ) (fig. . ). according to camel owners in the butana region of sudan, this disease has never been observed before in their herds (gitao et al. b ). the most important and prevalent disease of camels, trypanosomiasis (surra) caused by trypanosoma evansi, has been reported from the canary islands, spain, and recently from france (molina et al. ; gutierrez et al. ) . eimeria spp. have been introduced by importations of camels to europe, e.g., e. cameli (bornstein, personnel communication) . camels harbor several tick species, and some are important vectors of pathogens; protozoal, virus, and bacteria spp. cause tick paralysis and toxicosis (see above). however, their role of transmitting these pathogens to camelids seems to be much less important than it is to other animals and humans (bornstein ) . lately alkhurma hemorrhagic fever virus (ahfv) was isolated in an ornithodoros savignyi, the sand sampan, from saudi arabia (charrel et al. ). this soft tick has a wide distribution in arid lands and may lay dormant for long periods during harsh conditions. the tick infests many different hosts including camels as well as humans. the ahfv causes an extremely severe hemorrhagic fever in humans with a case fatality rate of > %. about human cases have been diagnosed with the infection in saudi arabia (charrel et al. ). the authors associate these or some of these cases with tick bite history. the above is one of many examples of emerging diseases transmitted by ticks and other arthropods (phylum arthropoda including the class insecta). the ahfv belong to tick-borne flaviviruses, which are among the medically most important arboviruses in asia and europe. some are very important as human and animal pathogens; others have not yet been associated with human or animal diseases. changes in human behavior, animal husbandry, land use, and/or climate may change the actual geographical distribution pattern and transmission intensity. this is already taking place, and it is often related to the present climate change. tick-borne flaviviruses and other arboviruses may increase in medical and veterinary importance as, e.g., in the case with bluetongue virus (see below). increasing numbers of south american camelids (sacs), particularly alpaca (vicugna pacos) and llama (lama glama), are being imported to various countries outside of south america, including europe, for wool (fiber) production, breeding, and as pack and companion animals. these newly introduced species have proved to be susceptible to "old" and new pathogens in their new environments. three viral diseases can be regarded as emerging infections in nwcs. the bvdv is not limited to cattle, but may be detected in various species. there is documentation of infection of alpacas resulting in reproductive loss and illness. kim et al. ( ) isolated bvdv from persistently infected alpacas and showed that unique genotypes of the virus may be maintained in the alpaca population even though camelids are susceptible to infection by other genotypes. there is clear evidence that the disease has been present in north american alpaca herds since at least and likely originated from bvdv-infected cows (van amstel and kennedy ). the bluetongue virus (btv) is an orbivirus with known sero-variants and is present worldwide. it exists in a broad band around the world covering large parts of the americas, africa, southern asia and northern australia (mellor et al. ) . occasionally it has occurred on the southern borders of europe. the btv is transmitted by midges (culicoides spp.) and naturally infects domestic and wild ruminants. the disease is considered to be one of the most important infections of domestic livestock. it is quite severe in sheep, less so in cattle. in june , btv appeared in northern europe for the first time (carpenter et al. ) and successfully wintered. subsequently it caused substantial losses in livestock in and . the virus has never previously occurred so far north anywhere in the world (mellor et al. ) . the explanation to this dramatic change in the epidemiology of bt is many, but one is linked to the recent extension in the distribution of its main vector(s) culicoides imicola and perhaps new culicoides vector(s) and to the ongoing climatic change ). alpacas and llamas are susceptible to btv infections, but rarely show significant clinical signs. however, they remain infectious for several weeks and may thus serve as reservoirs of infection. already rivera et al. ( ) showed that camelids can be infected with btv. about sampled "healthy" alpacas were positive for specific antibodies against bvt. although camelids are considered a "low-risk species," there are reports of cases, e.g., during the recent outbreak of bt in europe (henrich et al. ) . one alpaca in the area that was affected in germany during this outbreak was infected within a radius of km from clinically btvinfected sheep (with high mortality) and cattle. ortega et al. ( ) described a fatal btv infection in an alpaca (vicugna pacos) in california. meyer et al. ( ) described a lethal btv infection in llamas. vaccines are available and are used for ruminants. they are not licensed for sacs but may be used (zanolari et al. ) and are recommended by many. recently, a novel coronavirus possibly associated with acute respiratory syndrome in alpacas in california, , was reported . despite epidemiological evidence of bvdv, bt, and coronavirus infections in nwcs, current knowledge regarding the impact of these diseases is incomplete. the small liver fluke or the lancet fluke (dicrocoelium dendriticum) is rarely found in camelids. however, natural infections with this intriguing parasite have been reported from a few countries in alpacas in europe, switzerland, germany (wenker et al. ) , and recently sweden (de-verdier et al. ) . infection rates are most probably rel. high leading to rel. few but significant mortalities. llamas and alpacas may act as aberrant hosts to some parasites. in the usa, e.g., llamas cohabiting with the common white-tailed deer (odocoileus virginianus) may be infected with a meningeal worm (parelaphostrongylus tenuis), a nematode-causing neurological disease in the aberrant hosts (fowler ) . a review of camel brucellosis descriptive and spatial epidemiology of rift valley fever outbreak in yemen replication and shedding of mers-cov in upper respiratory tract of inoculated dromedary camels the genome of camelpox virus seroprevalence of brucellosis in animals and human populations in the western mountains region in libya middle east respiratory syndrome coronavirus infection in dromedary camels in saudi arabia recovery from severe novel coronavirus infection pathology and molecular diagnosis of paratuberculosis of camels risk factors associated with camel brucellosis in jordan the first outbreak of camelpox in syria the first isolation and molecular characterization of camelpox virus in ethiopia smallpox-like viruses from camels in iran differentiation of smallpox and camelpox viruses in cultures of human and monkey cells zoonotic cases of camelpox infection in india melioidosis in camels isolation and characterization of indian isolates of camel pox virus biological standard commission multiple virus lineages sharing recent common ancestry were associated with a large rift valley fever outbreak among livestock in kenya during skin diseases of camels, in; camel keeping in kenya parasitic diseases culicoide and the emergence of bluetongue virus in northern europe alkhurma hemorrhagic fever virus in ornithodoros savignyi ticks mers coronaviruses in dromedary camels transmission and evolution of the middle east respiratory syndrome coronavirus in saudi arabia: a descriptivegenomic study identification of a novel coronavirus possibly associated with acute respiratory syndrome in alpacas (vicugna pacos) in california rift valley fever in kenya: the presence of antibodies to the virus in camels (camelus dromedarius) mysterious mortality in camels (camelus dromedarius) in borana, ethiopia: evidence of its association with reproductive age groups lilla leverflundran -första fallet hos alpacka i sverige (the first case of the lancet fluke (dicrocoelium dendriticum) in swedish alpacas) clinical features and virological analysis of a case of middle east respiratory syndrome coronavirus infection camelpox virus kay- - , a novel nucleoside analogue inhibitor of orthopox viruses in vivo phocine distemper virus in seals, east coast comprehensive phylogenetic reconstructions of rift valley fever virus: the northern mauritania outbreak in the camelus dromedarius species proc int camel symp 'camel science and development for sustainable livestock medicine and surgery of south american camelids: llama a clinic-pathological study on spontaneous paratuberculosis in camels in saudi arabia genome-wide analysis of the emerging infection with mycobacterium avium subspecies paratuberculosis in the arabian camels (camelus dromedarius) outbreaks of dermatophilus congolensis infection in camels (camelus dromedarius) from the butana region in eastern sudan camel dermatophilosis in kenya, sudan and saudi arabia camel sudden death syndrome: outbreak of an unknown camel disease in the horn of africa the sequence of camelpox virus shows it is most closely related to variola virus, the cause of smallpox trypanosoma evansi recent outbreaks in europe brucellosis -regionally emerging zoonotic disease middle east respiratory syndrome coronavirus in dromedary camels: an outbreak investigation middle east respiratory syndrome (mers) coronavirus seroprevalence in domestic livestock in saudi arabia lethal bluetongue virus infection in an alpaca abd el-halim mm, fatebia mm ( ) studies on prevalence of rinderpest and peste des petits ruminants antibodies in camel sera in egypt camel pox and its risk to the human population camel contagious ecthyma: risks in young calves camel papillomatosis in the sudan clinical and epizootiological features of camelpox in eastern sudan an outbreak of peste des petits ruminants (ppr) in camels in the sudan mers-cov in upper respiratory tract and lungs of dromedary camels, saudi arabia genotyping and phylogenetic analysis of bovine viral diarrhea virus isolates from bvdv infected alpacas in north america disseminated rhodococcus equi infection in dromedary camels (camelus dromedarius) a study of camelpox in somalia asian lineage of peste des petits ruminants virus camels -a compendium. sydney post graduate foundation bluetonge in europe and the mediterranean basin: history of occurrence prior to human infection with mers coronavirus after exposure to infected camels, saudi arabia lethal bluetongue virus serotype infection in llamas antibodies against mers coronavirus in dromedary camels the emergence of the middle east respiratory syndrome coronavirus seroprevalence of trypanosoma evansi in dromedaries (camelus dromedarius) from the canary islands (spain) using an antibody ab-elisa molecular investigation and cultivation of camelpox virus in iran brucellosis in camels (camelus dromedarius) in darfur, western sudan rift valley fever outbreak, mauritania, : seroepidemiologic, virologic, entomologic, and zoologic investigations middle east respiratory syndromecoronavirus (mers-cov) in dromedary camels manual of diagnostic tests and vaccines for terrestrial animals (terrestrial manual). office international des épizooties brucellosis in camels, cattle and humans: associations and evaluation of serological tests used for diagnosis of the disease in certain nomadic localities in sudan fatal bluetongue virus infection in an alpaca (vicugna pacos) in california seroepidemiology for mers coronavirus using microneutralisation and pseudoparticle virus neutralization assays reveal a high prevalence of antibody in dromedary camels in egypt middle east respiratory syndrome coronavirus (mers-cov) serology in major livestock species in an affected region in jordan serological survey of viral antibodies in the peruvian alpaca (lama pacos) international disease monitoring descriptive and spatial epidemiology of rift valley fever outbreak in yemen investigations on a new pathological condition of camels in ethiopia detection of antibodies of rinderpest and peste des petits ruminants viruses (paramyxoviridae, morbillivirus) during a new epizootic disease in ethiopian camels (camelus dromedarius) bovine viral diarrhea infections in new world camelids -a review infectious diseases of the horse camelid brucellosis: a review dermatophilose in renndromedaren -fallbereicht melioidosis in a seven year old camel. a new disease in the united arab emirates (uae) natural burkholderia mallei infection in dromedary bluetongue in europe: past, present and future molecular characterization of enzootic camel pox in eastern province of kingdom of saudi arabia humoral response to inactivated bluetongue virus serotype- vaccines in south american camelids key: cord- -fo lq sb authors: zakaria, nasriah; alfakhry, ohoud; matbuli, abeer; alzahrani, asma; arab, noha samir sadiq; madani, alaa; alshehri, noura; albarrak, ahmed i title: development of saudi e-health literacy scale for chronic diseases in saudi arabia: using integrated health literacy dimensions date: - - journal: int j qual health care doi: . /intqhc/mzy sha: doc_id: cord_uid: fo lq sb objective: health literacy has become a global issue, and it is important that patients and individuals are able to use information technology to access health information and educational services. the research objective is to develop a saudi e-health literacy scale (sehl) for measuring e-health literacy among saudis suffering from non-communicable diseases (ncd). methods: overall, relevant papers in related interdisciplinary fields were reviewed to select the most useful literacy dimensions. from these articles, we extracted the most common dimensions used to measure e-health literacy across the disciplines. multiple workshops with multidisciplinary team members reviewed and evaluated items for sehl. results: four key aspects of e-health literacy—use of technology/media, information-seeking, usefulness and confidence—were identified and integrated as e-health literacy dimensions. these will be used to measure e-health literacy among saudi patients with ncds. a translation from arabic to english was performed in order to ensure that translation process was accurate. a sehl scale was developed to measure e-health literacy among saudi patients. by understanding e-health literacy levels, we will be able to create a patient-education system to be used by patients in saudi arabia. conclusions: as information technology is increasingly used by people of all ages all over the world, e-health literacy has been identified as a key factor in determining health outcomes. to date, no comprehensive scale exists to assess e-health literacy levels among speakers of arabic, particularly among people with ncd such as diabetes, cardiovascular diseases and hypertension. literacy is defined as the ability to read and write, whereas health literacy refers to the ability to understand and use health-related information to achieve good health [ ] . e-health literacy refers to the ability to use information technology (it) to improve health outcomes. this study focuses on e-health literacy among patients with non-communicable diseases (ncds). worldwide, million people have died from ncds. in saudi arabia, ncds accounted for % of the national mortality rate [ ] . a major public health problem is diabetes, which is one of the four ncds prioritized by the world health organization (who) [ ] . the prevalence of diabetes has almost doubled globally since , and affecting . % of the world's population in [ ] . prevention requires patients to understand steps and procedures for monitoring their diabetes, and management of diabetes may involve taking insulin or other medication in a consistent manner. therefore, who recommends addressing the key gaps in patients' knowledge in the disease and related health issues. with technology being available literally in everyone's hand, e-health literacy is a key component for disseminating knowledge and ensuring that patients maintain good health. no studies have explored e-health literacy among patients in the middle east. among middle eastern countries, saudi arabia has the highest number of people with internet access: . % of the population [ ] . saudis, especially the younger generation, are increasingly using it to access health information [ ] , and health practitioners and institutions are frequently accessing the internet for information. during the mers corona-virus outbreak in - , for example, the ministry of health used an e-platform, namely twitter, to alert the public about the epidemic as well as to promote health programs. in high-income countries, healthcare efforts can be maximized using it. there are numerous studies on the use of e-health or health it for prevention, treatment, health maintenance and wellness. for example, mobile applications (apps) have been developed to provide information on how to treat cardiovascular issues and diabetes. wellknown websites such as webmd [ ] and the us centers for disease control (cdc) [ ] offer education and information regarding a wide range of health topics. other health portals that are focused on individual health issues, such as the diabetes center, demonstrate the positive impact of it on health maintenance for diabetes patients. despite evidence of high it use, there is no published evidence about whether the saudi population is using it to obtain health information or make decisions, especially regarding ncds such as diabetes, cardiovascular issues and hypertension. further, no studies have measured saudis' e-health literacy. the study was thus carried out to fill the gap in research in this particular area. illiteracy is still a major problem worldwide, especially as it relates to health and healthcare. many studies have found that almost half of the world's adult population is deficient in reading, writing, and computing skills. roughly % of english-speaking patients have inadequate health literacy skills, resulting in poor healthcare, inadequate medical information, and consequently, lack of treatment. this increases the prevalence of diseases, affects patients' overall health and increases patients' chances of hospitalization [ ] . literacy in e-health involves a variety of skills, from choosing which program to use (internet-based or stand-alone), knowing how to use a search engine, and being able to read and evaluate an article or blog post. furthermore, it is helpful to know how to find and use widgets and utilities available on the web, stay up-to-date on health news, understand medical terminology and jargon, and know how to interpret graphs, charts and statistics. one recently proposed framework for literacy [ ] shows different sets of core skills that can be measured in e-health users and divides literacy into traditional (reading and numerical) literacy, health literacy, science literacy, computer literacy, information literacy and media literacy. science literacy means that a person can understand accounts of scientific experiments in healthcare like what is meant by 'a randomized trial'. health literacy is also needed for a person to interpret health outcomes independently, without professional help. according to another study by chew [ ] , having computing and engineering skills is also a measure of health literacy. nutbeam [ ] defined health literacy from both personal and social aspects and proposed several dimensions such as functional, critical and communicative literacy. paakkari and paakkari [ ] , divided health literacy into theoretical knowledge, practical knowledge, critical thinking, self-awareness and citizenship. ishikawa's et al. [ ] work was an extension of nutbeam's work [ ] and paakkari and paakkari [ ] , recommended that researchers use multiple criteria to evaluate health literacy. similarly, chan et al. [ ] suggested that health literacy should encompass multiple forms of literacy, including traditional, health, science, computer, information and media literacies. many previous studies have explored how health literacy affects patients with chronic illness. low literacy is associated with adverse health outcomes and is common, especially in elderly patients. poor health status is more closely associated with low health literacy than with education, income, ethnic background or any other variables. in addition, patients with low health literacy may become ill or be hospitalized more frequently than patients with high or adequate health literacy [ ] . the relationship between low health literacy and illness has been supported in studies about acute and chronic diseases, which show that health literacy skills have a direct impact on health status outcomes [ ] . the ability to read is, all by itself, a predictor of all-cause mortality and cardiovascular death among the elderly. reading fluency is a more powerful variable than education for examining the association between socioeconomic status and health. chang et al. [ ] posited a relationship between health literacy and two outcome measurements: knowledge and prevention behavior. the most recent study by kim and lee [ ] concluded that diabetes management that is sensitive to health literacy is more effective in reducing hba c levels in patients. all evidence indicates that health literacy can have a strong impact on patient care. the more literate the patient, the better he or she will take care of himself or herself. health literacy is an independent variable in this study. in this study, we describe the development of a saudi e-health literacy scale (sehl) for measuring e-health literacy among saudis suffering from ncds, especially diabetes and cardiovascular diseases. such a scale could be used to assess e-health literacy levels to assist healthcare providers in creating effective e-health interventions for these patients (figure ). we began with a literature review, using pubmed and google scholar to retrieve papers on literacy, health literacy and e-health literacy scales. the search was done from october till june and the list of search terms is listed in table . we eventually pared down the selection from papers to . these papers met our inclusion criteria which were: (i) the topic must be either health literacy or e-health literacy, (ii) the paper must have been cited three or more times and (iii) all papers were included in systematic reviews by ishikawa et al., alsayah and boren [ , , ] . the alsayah et al.'s paper [ ] included all the gold standards in health literacy such as test of functional health literacy in adults ( tofhla), rapid estimates of adult literacy in medicine (realm), single item literacy scales (sils) and newest vital signs (nvs). we also looked at the most recent publications by alsayah et al. [ ] and current papers on e-health literacy such as watkins [ ] . we revisited health literacy skills instruments (hlsi) [ ] and the e-health literacy scale (e-heals) [ ] to understand e-health literacy in depth. we decided that we could not use the e-heals scale because it only looks at literacy on the internet, and because most e-heals work must be accompanied by an it skills test [ , , ] . therefore, the e-heals scale was deemed unsuitable for the saudi nationwide study. we conducted two workshops, in january and may , respectively, to gain a better understanding of the selected studies and make sense of the e-health literacy and health literacy dimensions discussed in them. the process of selecting dimensions, extracting items and scales, and assembling a sehl is illustrated in figure . the workshop attendees were health informatics professionals, health educators and clinicians. a matrix (table ) was created to extract the dimensions used in each paper. as we tried to match the papers with the dimensions, we found that some overlapping concepts were used in similar ways; thus, similar concepts were merged into single dimensions. for example, under 'decision making,' we found four areas: understanding, usefulness, remembering and communication. communication was further subdivided into pronunciation and verbalization, reading comprehension, numeracy, decision making, confidence, health-information seeking, navigation and need for assistance. the dimensions for our sehl scale were finalized as follows: (i) usefulness/understanding, (ii) confidence/needs assistance, (iii) information seeking and (iv) use of technology and media. we then list all the related items and scales, and conducted another workshop to clarify the meanings of the items in each category. during this workshop, we also revisited the reasons behind sehl. we considered the following: how patients sought information, how well they understood it, how useful the information was, how comfortable patients were with new health information, and how they used media and technology for health information. the research group felt that it was important that the logistics of collecting data be straightforward and that the scale be easy to be read. it was presented in a language simple enough to suit the culture and context of our study (table ) . in reviewing the papers for table , we discovered some common literacy dimensions used in both health literacy and e-health literacy assessment. for example, the chinese health literacy scale for diabetes (chlsd), developed by leung et al. [ ] for china's population, adapted other gold-standard scales such tofhla to measure the 'understanding' and 'applying' aspects of literacy. another study by garcia-marcinkiewicz et al. [ ] measured health literacy among patients who had undergone anesthesia, in terms of confidence, usefulness and understanding. garcia-marcinkiewicz used a variety of likert scales, such as 'disagree/agree' and 'never/frequently'. our selected papers also included a study done in taiwan by chang et al. [ ] , which measured media literacy as it related to tobacco and alcohol use. we adapted the media literacy dimension used by chang et al., since patients may receive health information from media content such as youtube, educational videos or webtv. an important study in health literacy by nutbeam, paakkari and paakkari, and ishikawa [ , ] used three literacy dimensions: functional, communicative and critical. functional literacy deals with word recognition and comprehension, communicative literacy deals with how patients understand and communicate information about their disease to others, and critical literacy refers to how patients analyze information and make decisions about their disease. xie [ ] investigated the use of the e-heals scale to measure e-health literacy. e-heals was introduced by skinner based on the selected papers, we chose four literacy dimensions for our sehl scale: (i) use of technology/media: this dimension asks patients how fast they learn to navigate websites and how often they make mistakes when using a web page. follow-up questions measure how often they see chronic illnesses represented in various media on the internet. (ii) information seeking: this dimension explores what information patients find, how and where they find it, and asks their preferences regarding obtaining information about health. many of the items included in this section come from the e-heals scale. (iii) understanding/usefulness: this dimension asks patients how useful the information is to them and whether they have difficulty understanding the information given. (iv) confidence/needs assistance: this dimension measures how confident patients are in filling out forms and whether they need any assistance with reading and understanding the materials given to them at the hospital. our effort to develop sehl is consistent with a recent study by bautista and wee [ ] that suggests researchers should define the operational measure for e-health literacy and measure the validity and reliability of e-health literacy scales. to conduct a large-scale study on health education regarding ncds in saudi arabia and other arabic-speaking countries, we needed to develop an e-health literacy scale suitable for our objectives and context. we were able to aggregate a scale that measures e-health literacy based on four dimensions: decision making, information seeking, confidence, and use of media and technology. we did this by reviewing previous studies in health literacy and e-health literacy and by conducting workshops to propose a new scale suitable for measuring e-health literacy levels among the saudi population. this study may later be extended to other arabic-speaking countries, in which no e-health literacy research has been previously done. there are arabic-speaking countries, which represent a total population of~ million. one study published by giacaman et al. [ ] found a high level of health literacy in israeli-occupied palestinian areas as compared to several arab countries, but no measurements of e-health literacy were conducted. besides the research noting the lack of an available scale, no major work has been done towards measuring e-health literacy at the population level in saudi arabia. the world fact website states that basic literacy (reading and writing) levels in saudi arabia are % (compared to the united states with %). however, e-health literacy-defined as the ability to read, write and understand health information using the internet and other it-is only % in the usa [ ] . no other nation has reported its ehealth literacy at the population level. the development of sehl will contribute to our knowledge of e-health literacy as it relates to ncds in the saudi population. the national study that will be conducted in saudi arabia can help determine the prevalence of health information seeking e-health literacy among patients with ncd. in terms of the public health field, this e-health literacy research can help organization build a better patient education system that would promote prevention of ncds. this study also analyzed literacy dimensions identified in other wellknown scales in alsayah et al. [ ] and found that some of these tools cannot be applied directly in our context. the integration of several available scales was important to ensure that we accurately measure technology, information, and uses of health information for patients. the limitation of the study is that our literature review looked only at publications and scales written in english. we may have therefore missed some important scales created in other languages. future work will involve conducting focus groups with experts to finalize the sehl, and test the new scale's validity and reliability with patients suffering from ncds at king khalid university hospital, riyadh, saudi arabia. what skills should be included when assessing health literacy? who. global report on diabetes executive summary indicators in ksa the impact of obesity related websites on decision making among students in saudi arabia measuring functional, communicative, and critical health literacy among diabetic patients a framework for characterizing ehealth literacy demands and barriers developing a new scale for e-health literacy health literacy as a public health goal: a challenge for contemporary health education and communication strategies into the st century. health promot int health literacy as a learning outcome in schools the association of medical exposure and media literacy with adolescent alcohol and tobacco use health-literacy-sensitive diabetes self-management interventions: a systematic review and meta-analysis. world views evid based measuring health literacy in individuals with diabetes: a systematic review and evaluation of available measures a review of health literacy and diabetes: opportunities for technology ehealth literacy interventions for older adults: a systematic review of the literature measuring health literacy: a pilot study of a new skills-based instrument experimenting on the impact of learning methods and information presentation channels on older adults' e-health literacy does the ehealth literacy scale (eheals) measure what it intends to measure? validation of a dutch version of the eheals in two adult populations older adults, e-health literacy, and collaborative learning: an experimental study development and validation of chinese health literacy scale for diabetes health literacy and anesthesia: patients' knowledge of anesthesiologist roles and information desired in the preoperative visit ehealth literacy: essential skills for consumer health in a networked world drug literacy in iran: the experience of using 'the single item health literacy screening (sils) tool from solving a health problem to achieving quality of life: redefining ehealth literacy health status and health services in the occupied palestinian territory health literacy and women's health-related behaviors in taiwan measuring actual ehealth literacy among patients with rheumatic diseases: a qualitative analysis of problems encountered using health . and health . applications effects of an ehealth literacy intervention for older adults association of ehealth literacy with cancer information seeking and prior experience with cancer screening association of health literacy with self-management behavior in patients with literacy and diabetes self-management health literacy and nurses' communication with type diabetes patients in primary care settings saudi e-health literacy (sehl) prototype in english decision making (understanding and usefulness) a. how useful is it for you to receive information about chronic illness? key: cord- - mf wi authors: alghamdi, saleh; atef-shebl, nada; aslanpour, zoe; berrou, ilhem title: barriers to implementing antimicrobial stewardship programmes in three saudi hospitals: evidence from a qualitative study date: - - journal: j glob antimicrob resist doi: . /j.jgar. . . sha: doc_id: cord_uid: mf wi objectives: this study explored antimicrobial stewardship programme (asp) team members’ perspectives regarding factors influencing the adoption and implementation of these programmes in saudi hospitals. methods: this was a qualitative study based on face-to-face semistructured interviews with healthcare professionals involved in asps and activities across three ministry of health (moh) hospitals in saudi arabia (n = ). interviews were also conducted with two representatives of a general directorate of health affairs in a saudi region and two representatives of the saudi moh (n = ) between january–february . results: despite the existence of a national strategy to implement asps in saudi moh hospitals, their adoption and implementation remains low. hospitals have their own antimicrobial stewardship policies, but adherence to these is poor. asp team members highlight that lack of enforcement of policies and guidelines from the moh and hospital administration is a significant barrier to asp adoption and implementation. other barriers include disintegration of teams, poor communication, lack of recruitment/shortage of asp team members, lack of education and training, and lack of health information technology (it). physicians’ fears and concerns in relation to liability are also a barrier to their adoption of asps. conclusion: this is the first qualitative study exploring barriers to asp adoption and implementation in saudi hospitals from the perspective of asp team members. formal endorsement of asps from the moh as well as hospital enforcement of policies and provision of human and health it resources would improve the adoption and implementation of asps in saudi hospitals. the high prevalence of antimicrobial resistance (amr) and the emergence of rare and multidrug-resistant bacterial strains are major public-health threats in saudi arabia and other arab gulf countries, where one of the largest expatriate populations resides and more than million people travel annually for pilgrimage and umrah [ , ] . a recent review by zowawi highlighted the worrying reports of extended-spectrum β-lactamase-producing isolates among escherichia coli and klebsiella pneumoniae and the prevalence of carbapenem-resistant acinetobacter baumannii [ ] . with saudi hospitals reporting soaring amr rates, widespread misuse of antimicrobials and fears of resistance to last-resort antibiotics [ , ] , interventions are urgently required to curb inappropriate antimicrobial use and amr rates. implementing antimicrobial stewardship programmes (asps) in saudi hospitals has been recommended to optimise the use of antimicrobials and to reduce amr rates [ , ] . the potential of these interventions has been recognised by the saudi ministry of health (moh) through the introduction of a national antimicrobial stewardship plan as part of the arab gulf regional strategy to reduce the threat of amr [ ] . at a hospital level, evidence suggests the implementation of asps in some saudi tertiary hospitals [ ] [ ] [ ] and these asps are mainly led by infectious diseases (id) consultants, with limited input from microbiologists and hospital pharmacists [ , ] . however, due to the shortage of id consultants and microbiologists [ ] , these antimicrobial stewardship initiatives face sustainability challenges in tertiary care and are less likely to be implemented in secondary care where adoption of asps remains low [ ] . collaborations and the formation of asp teams, including microbiologists, hospital pharmacists, physicians, nurses and infection control practitioners, could increase the capacity of hospitals to adopt asps and improve their implementation [ ] . although various studies have explored asp team members' perspectives on programme adoption and implementation in healthcare systems where members' roles are well developed, data from healthcare systems such as saudi arabia, where asp teams are novice, remain scarce. understanding the experiences and perspectives of physicians, pharmacists, microbiologists, infection control practitioners, hospital managers, nurses and moh personnel of asp adoption could enhance the adoption of asps in saudi hospitals. therefore, this study aimed to explore the current asp perspectives and experiences in saudi moh hospitals in order to identify factors influencing their adoption through a qualitative study. a sequential mixed-methods project using both qualitative and quantitative methods was conducted; the results of the qualitative aspect of the project are presented here. this was the first part of the project and involved semistructured face-to-face interviews with healthcare professionals from three randomly selected moh hospitals: a local -bed hospital; a regional -bed hospital; and a central -bed hospital. all three hospitals are located in a saudi region (south of saudi arabia) or its outskirts. in each setting, asp team members were identified and contacted. representatives from the general directorate of health affairs in the region (infection control department and pharmaceutical care department) and the saudi moh also participated in this study. one of the authors (sa) conducted the interviews in january and february using a semistructured interview guide. this was developed based on a review of the literature and was validated by a committee of three asp pharmacists and two id consultants. it was then piloted in a convenience sample of participants from three moh hospitals. the guide comprises open-ended questions to explore the experience and perspectives of physicians, hospital pharmacists, microbiologists, infection control practitioners, nurses, hospital managers and moh representatives in relation to the adoption and implementation of asps in saudi moh hospitals as well as the barriers influencing asp implementation. further probing questions may have been asked based on participants' responses. the identified factors influencing asp adoption in saudi moh hospitals were further explored in the quantitative aspect of the project through a national hospital survey. all interviews were transcribed verbatim and the transcripts were compared with the original tape to review for quality and accuracy. data were analysed independently by two of the authors (sa and ib) and were subjected to various stages of inductive coding for thematic development [ ] . the coders met regularly to review coding and to derive themes. the study was approved by the health and human sciences ethics committee of the university of hertfordshire (hatfield, uk). official permission was obtained from participating hospitals, and all participants signed informed consent before taking part in the study. a total of interviews were conducted. these included interviews with physicians, nurses, hospital pharmacists, infection control practitioners, id consultant, microbiologist and hospital managers representing the three saudi moh hospitals. the head of the infection control department and the head of the pharmaceutical care department in the general directorate of health affairs in the saudi region as well as consultant clinical microbiologist and clinical pharmacist representing the saudi moh departments of infection control and pharmaceutical care were also interviewed. the participants had a median of years of practice (range - years). interviews lasted up to min. details of the participating hospitals are summarised in table and details of the participants are summarised in tables and . several main themes emerged from the interviews, including the current state of asps in hospitals as well as barriers to asp implementation in saudi moh hospitals; these were further divided into subthemes. this study suggests that formulary restriction is the main asp strategy adopted in saudi moh hospitals. furthermore, adoption and implementation of asps is hindered by three sets of barriers. first, sociopolitical context barriers, including lack of adherence to guidelines and legislation. second, healthcare organisation-related barriers such as lack of management support, disintegration, poor communication, lack of recruitment/shortage of asp team members, lack of education and training, and lack of health information technology (it). and third, healthcare professionals' barriers relating to their fears and concerns. the following sections provide a detailed description of the emerging themes, which are summarised in table . the front-end strategy of formulary restriction is the main asp strategy adopted in all three hospitals. the hospitals' asps include an antimicrobial prescribing policy in which antimicrobials are classified into three categories (a, b and c) as follows. category a antimicrobials: unrestricted availability of these antimicrobials; examples include amoxicillin, metronidazole and nystatin. category b antimicrobials: restricted availability of these antimicrobials and approval of a specialist is required before they are dispensed. they are usually prescribed by consultants or their designees (specialist or resident) following the consultant's guidance. examples of these antimicrobials include azithromycin, gentamicin and rifampicin. category c antimicrobials: antimicrobials in this category are permitted only for specific conditions such as sepsis or serious infections caused by multidrug-resistant micro-organisms. they are usually prescribed by a consultant and this requires the completion of a justification form. examples of these antimicrobials include colistin, meropenem and micafungin. in addition to the antimicrobial prescribing policy, the hospitals front-end strategy also includes regimens for the treatment of common infections. interestingly, there are no written rules for switching from intravenous to oral administration of antimicrobials; it is usually up to the treating physician to determine the duration of treatment and the route of administration. (table ) despite the formal existence of this asp strategy in the participating hospitals, interviewees stressed that lack of adherence to antimicrobial policies and guidelines as a significant barrier to asp adoption and implementation in hospitals (t q - ). lack of adherence to asp policies and guidelines is due to three main factors. first, physicians are not always aware that such policies exist as this is not a routine part of their orientation programme (t q - ). second, the asp guidelines and policies are not always accessible electronically (t q ) as the policies are distributed across the departments (by either the infection control department or pharmacy or both) often in a paper format that only a few staff members have direct access to. third, poor enforcement and implementation of asp policies is a significant contributing factor to the lack of adherence to this strategy. participants suggested vertical enforcement by moh and hospital management as a potential approach to improving engagement of physicians with the asp strategy (t q - ). the lack of management awareness of asps and strategies has been suggested to hinder the successful adoption and implementation of asps in hospitals (t q - ). furthermore, the management team is not convinced of the benefits of asps in relation to antimicrobial consumption, reducing rates of amr and improving patient outcomes (t q ). this is critical as the lack of top management support and commitment have been identified as significant barriers to asp adoption and implementation in saudi moh hospitals (t q - ). top management here can, among other initiatives, increase the visibility of the hospital asp strategy and enforce adherence to its policies. healthcare professionals involved in delivering antimicrobial stewardship are working in silos (t q - ), reflecting a disintegrated structure that hinders effective teamworking of antimicrobial stewardship teams. in addition to teams working in silos, many of the interviewed physicians further highlighted that 'silo mentality' exists even among themselves (t q - ). furthermore, there appears to be the need for the pharmacy department and pharmacists to co-ordinate antimicrobial stewardship efforts among physicians and nurses (t q ). healthcare professionals also identified poor communication among the key antimicrobial stewardship players as a barrier to asp adoption. pharmacists in particular appear to be key initiators and co-ordinators of antimicrobial stewardship communication (t q - ). it is unclear whether this communication is a reason for the disintegrated teams or a consequence of such disintegration. the shortage of asp team members has also been suggested as a significant barrier to asp adoption and implementation in saudi moh hospitals. the lack of clinical pharmacists has been particularly blamed for the modest levels of adoption of asps in the participating hospitals. the participants particularly expressed that clinical pharmacists will be able to advise on the appropriate use of antibiotics and, most importantly, follow up on policy implementation and enhance prescribing practices (t q - ). the shortage of id consultants has also been associated with poor adoption and implementation of asp strategies, as not all moh hospitals manage to recruit id consultants, and the recruited few are often not retained or are inundated with allocated cases from neighbouring hospitals (t q - ). the lack of microbiologists and laboratory equipment can also be a barrier to implementing asps (t q ). however, participants recognised that recruiting specialist staff will not be sufficient as these need to work together as a team to adopt and implement asps in hospitals (t q ). education and training have been suggested by participants as major contributors to successful asp adoption and implementation. workshops to raise awareness of amr, and education and training related to antimicrobial policies and guidelines as well as good antimicrobial stewardship need to be part of the adoption and implementation strategy (t q - ). furthermore, physicians highlighted that orientation programmes for new starters and locums do not include local antimicrobial policies guidelines and this has contributed to the often inappropriate prescribing of antimicrobials (t q ). the participants, particularly nurses, also emphasised that raising awareness of amr as well as education on the appropriate use of antimicrobials should also be targeting patients in recognition of the patient and public contribution to amr (t q ). 'all of us should be involved. all of us have our own responsibility and accountability. it should not be like, only the nurses should do it, also doctors, at the same time microbiologists and pharmacy' q t : need for education and training 'you need a lot of training and education before the programme starts correctly' q 'there is need for awareness, there should be regular workshops. there should be some compulsory workshops that should be arranged and everyone should be attending' q 'we (doctors) need more training and ongoing education programmes that are related to antibiotics' q 'you want guideline, monitoring and educated staff to implement the (asp) programme' q 'they (doctors) need to have a good orientation regarding the antibiotic policy' q 'increase the awareness not only within the healthcare team, but also with the family and patient' q t : lack of health information technology (it) 'most hospitals don't have e-systems so they can't tell us about their consumption' q ' % of hospitals don't have a good it system. out of hospitals, % do not have electronic prescription' q 'the it system is useless because it dispenses antibiotics without any identification . . . if the it system is effective so you insist that the prescription should not be completed unless the diagnosis, viral, is written in. if there is viral infection the programme itself won't respond to give you antibiotics' q 'you need a good system . . . the it system that we count on in all the communication between departments, between the id and the pharmacy, and we depend on it' q 'we cannot apply antibiotic stewardship if we don't have a good it system and we have good internal communication system between the concerned departments: the id, the pharmacy and the ward' q t : physicians' fears and concerns 'the patient improves so i don't want to change this antibiotic, because i am afraid that the patient can relapse' q 'i am worried about my patient, if the patient dies, i'm responsible for the patient' q 'in the end, doctors here fear to be accused of negligence' q 'i need the motivation and empowerment of the physicians. because they are afraid if they have any problems, they will not be protected from top management' q 'they don't consider the future, all they consider is the short term effect . . . i used three antibiotics, so i have covered the patient, and this patient will get better' q 'some doctors refuse to be challenged. he will say i have read about the topic and i know what i am doing' q 'because surgeons are not so good with antibiotics' q id, infectious diseases. the lack of health it in saudi moh hospitals has been suggested as a significant barrier to asp adoption. absence of electronic prescribing prevents monitoring of antimicrobial prescribing and antimicrobial consumption data capture (t q - ). furthermore, even if health it is integrated in hospitals, lack of a specialised electronic antimicrobial approval system hinders the adoption of antimicrobial stewardship (t q ). a sophisticated it system is also needed for efficient communication between the various departments and personnel involved in antimicrobial stewardship (t q - ); this may reduce the disintegration of teams and improve their communication. one interesting barrier to asp adoption in saudi moh hospitals is physicians' fears and concerns. one of the physicians' main concerns is the considerable liability pressure. physicians are often reluctant to change antimicrobials prescribing or to reduce the length of treatment as per guidelines fearing that the patient may deteriorate. in which case, the physician is resorting to defensive prescribing in fear of legal or administrative proceedings (t q - ). another concern is that the risks and benefits of antimicrobial prescribing are only considered for current patients and not future patients (t q ). the participants also highlighted that influencing physicians' prescribing of antimicrobials can be a difficult path, either due to poor enforcement of guidelines, the liability pressure on physicians, or their personal traits and behaviours (t q - ). national and regional legislation can improve the adoption and implementation of asps in hospitals [ ] . however, despite the introduction of a national asp strategy in , adoption and implementation in saudi moh hospitals remains low and slow (the progress of implementation has recently been reviewed by alomi [ ] ). the national asp strategy of has so far been merely 'academic' and it has not been accompanied by any enforcement measures. furthermore, the lack of national surveillance for antimicrobial use and amr rates in saudi arabia [ , ] decreases motivation to reduce inappropriate antimicrobial use and marginalises the issue of resistance. in addition to the lack of enforcement at a central level, the same is happening at hospital level. antimicrobial guidelines and policies exist but prescribers are either unaware of them, cannot easily access them or are not required to adhere to them. the lack of knowledge of standard treatment guidelines and poor enforcement efforts foster inappropriate antimicrobial use and increase the prevalence of amr [ ] . a qualitative study by algahtani et al. [ ] found that accreditation [ ] improved the process and implementation of change in hospitals and, in turn, improved the delivery of healthcare services and quality of care. lack of top management support has been identified as a significant barrier to asp adoption. hospital managers are responsible for organising healthcare services and ensuring ultimate safe practices through their actions, goals and behaviours [ ] . in saudi hospitals, managers tend to be mainly reactive rather than proactive and their role largely involves response to and ensuring compliance with rules and regulations set out by government [ ] . like in the case of it innovation adoption, for example, managers who are aware of the seriousness of amr and with previous experience of asps are more likely to adopt the innovation [ ] . without management support, the adoption, implementation and continuation of asps can be affected, as shown in previous studies [ , ] . in , sobczak reviewed integration and disintegration within organisations including healthcare. while integration refers to collaboration and co-operation within joint programmes and projects, disintegration relates to fragmentation and lack of co-operation [ ] . the latter has been suggested to hinder quality improvement initiatives in saudi hospitals [ ] . furthermore, the importance of interdepartmental collaboration within hospitals has been recognised in response to epidemics affecting saudi arabia and other countries in the region, including the outbreak of middle east respiratory syndrome coronavirus [ ] . the lack of interdepartmental collaboration within saudi hospitals is related to communication, which has also been identified as poor, and a significant organisation cultural barrier to quality improvement initiatives within saudi hospitals [ ] and others [ , ] . it can potentially improve interdepartmental communication and improve patient safety in hospitals [ ] . moreover, the use of sophisticated it systems that include computerised clinical decision support systems can improve antimicrobial prescribing practices and reduce the rates of healthcare-associated clostridium difficile infection [ ] . moreover, it systems that support the integration of electronic healthcare records (ehrs) can enhance the adoption and implementation of asps in healthcare settings [ ] . interestingly, lack of financial resources to fund it infrastructure was not identified as a factor in the study by hasanain et al. [ ] and was unclear in the study by aldosari [ ] . the size of the hospital, however, significantly affected the adoption of ehrs and sophisticated it infrastructure [ ] . in relation to asps, tertiary hospitals in saudi arabia are more likely to have reliable microbiology facilities and to recruit id physicians and clinical pharmacists, probably due to the availability of resources (financial and human). however, the remaining saudi hospitals continue to report understaffing and/or shortage of asp teams members, a barrier shared with hospitals in several other countries [ ] . these teams will be responsible for co-ordinating education and training of healthcare professionals within the hospital. this education and training role is a key strategy to tackle the inappropriate antimicrobial prescribing behaviours of physicians [ ] . this can be done, as part of a hospital-wide multifaceted approach, through dissemination of educational material [ ] , audit and feedback on performance [ ] , and manual and automated reminders [ ] . in the absence of enforcement of antimicrobial guidelines as well as lack of support from the hospital administration, physicians in saudi moh hospitals perceive that they have the sole responsibility for patients' safety and well-being. thus, physicians resort to prescribing broad-spectrum antimicrobials to prevent deterioration and complications. similar practices have been reported in other countries [ ] . leadership from the moh to enforce antimicrobial stewardship guidelines, and their enforcement from the hospital administration, are likely to address physicians' fears and concerns. prescribers are likely to consider the risks and benefits of antimicrobial prescribing for current as well as future patients [ ] . to our knowledge, this is the first qualitative study regarding asp adoption in saudi arabia and the whole gulf cooperation council region. however, there are limitations to this study. although different healthcare professionals involved in antimicrobial stewardship were interviewed, the sample was composed of staff who are aware of asps and thus there is a possibility that the results portrayed do not reflect the views of healthcare professionals who lack experience of asps. furthermore, the study was based on a small number of hospitals (n = ) that were not geographically representative of all saudi moh hospitals. a national survey, which forms the quantitative part of this project, involving all moh hospitals would improve our understanding of the state and the factors affecting asps adoption at a national level. several barriers to asp adoption and implementation in saudi moh hospitals were identified, including factors relating to the sociopolitical context of hospitals, organisational characteristics and healthcare professionals' barriers. the emphasis on enforcement of antimicrobial stewardship guidelines could not be more explicit; asp adoption and implementation in saudi hospitals must be formally endorsed by the moh and enforced and supported by the hospital administration to relieve physicians' liability pressures and to improve their antimicrobial stewardship practices. the lack of human and health it resources to support antimicrobial stewardship must be addressed before the benefits of asp adoption and implementation can be realised. the phd studentship of sa is funded by albaha university (albaha, saudi arabia). none declared. this study was approved by the health and human sciences ethics committee of the university of hertfordshire (hatfield, uk) [protocol no. lms/pgr/uh/ ]. official permission was obtained from participating hospitals, and all participants signed informed consent before taking part in the study. arab versus asian migrant workers in the gcc countries saudi ministry of health. statistical year book. saudi ministry of health antimicrobial resistance in saudi arabia. an urgent call for an immediate action antimicrobial use in neonatal units at king abulaziz medical city, riyadh, ksa, prospective observational study el-saed a. consumption of carbapenems in different intensive care units in a saudi tertiary care hospital national antimicrobial stewardship program in saudi arabia; initiative and the future antimicrobial stewardship program implementation in a medical intensive care unit at a tertiary care hospital in saudi arabia restrictive reporting of selected antimicrobial susceptibilities influences clinical prescribing a stepwise introduction of a successful antimicrobial stewardship program. experience from a tertiary care university hospital in western, saudi arabia hospital adoption of antimicrobial stewardship programmes in gulf cooperation council countries: a review of existing evidence the expanding role of antimicrobial stewardship programs in hospitals in the united states: lessons learned from a multisite qualitative study demonstrating rigor using thematic analysis: a hybrid approach of inductive and deductive coding and theme development the antimicrobial stewardship program in gulf cooperation council (gcc) states: insights from a regional survey who report finds systems to combat antibiotic resistance lacking the who policy package to combat antimicrobial resistance perception of hospital accreditation among health professionals in saudi arabia minister of health honors a number of jci-accredited moh hospitals factors affecting the climate of hospital patient safety: a study of hospitals in saudi arabia assessing the green supply chain management for the united arab emirates construction industry. green supply chain management for sustainable business practice the impact of clinical leadership on health information technology adoption: systematic review experiences and perspectives of implementing antimicrobial stewardship in five french hospitals: a qualitative study facilitators and barriers to implementing antimicrobial stewardship strategies: results from a qualitative study opportunities for and constraints to integration of health services in poland assessing the organizational characteristics influencing quality improvement implementation in saudi hospitals infection control and prevention practices implemented to reduce transmission risk of middle east respiratory syndrome-coronavirus in a tertiary care institution in saudi arabia implementing antimicrobial stewardship in the australian private hospital system: a qualitative study smartphones let surgeons know whatsapp: an analysis of communication in emergency surgical teams outcomes of multisite antimicrobial stewardship programme implementation with a shared clinical decision support system use of electronic health records and clinical decision support systems for antimicrobial stewardship electronic medical record systems in saudi arabia: knowledge and preferences of healthcare professionals rates, levels, and determinants of electronic health record system adoption: a study of hospitals in riyadh, saudi arabia human resources estimates and funding for antibiotic stewardship teams are urgently needed physicians' knowledge, perceptions, and attitudes toward antimicrobial prescribing in riyadh, saudi arabia the long-term outcomes of an antibiotic control program with and without education impact of an educational program on antibiotic use in paediatric appendectomy procedures effectiveness of education and an antibioticcontrol program in a tertiary care hospital in thailand understanding physician antibiotic prescribing behaviour: a systematic review of qualitative studies securing access to effective antibiotics for current and future generations. whose responsibility? the authors thank all of the healthcare professionals who agreed to give up their time to participate in this study. key: cord- -qbn i nq authors: alrasheed, hend; althnian, alhanoof; kurdi, heba; al-mgren, heila; alharbi, sulaiman title: covid- spread in saudi arabia: modeling, simulation and analysis date: - - journal: int j environ res public health doi: . /ijerph sha: doc_id: cord_uid: qbn i nq the novel coronavirus severe acute respiratory syndrome (sars)-coronavirus- (cov- ) has resulted in an ongoing pandemic and has affected over countries around the world. mathematical epidemic models can be used to predict the course of an epidemic and develop methods for controlling it. as social contact is a key factor in disease spreading, modeling epidemics on contact networks has been increasingly used. in this work, we propose a simulation model for the spread of coronavirus disease (covid- ) in saudi arabia using a network-based epidemic model. we generated a contact network that captures realistic social behaviors and dynamics of individuals in saudi arabia. the proposed model was used to evaluate the effectiveness of the control measures employed by the saudi government, to predict the future dynamics of the disease in saudi arabia according to different scenarios, and to investigate multiple vaccination strategies. our results suggest that saudi arabia would have faced a nationwide peak of the outbreak on april with a total of approximately million infections had it not imposed strict control measures. the results also indicate that social distancing plays a crucial role in determining the future local dynamics of the epidemic. our results also show that the closure of schools and mosques had the maximum impact on delaying the epidemic peak and slowing down the infection rate. if a vaccine does not become available and no social distancing is practiced from june , our predictions suggest that the epidemic will end in saudi arabia at the beginning of november with over million infected individuals, and it may take only days to end the epidemic after % of the population receive a vaccine. coronavirus, a genus of the coronaviridae family, are enveloped viruses with a large plus-stranded rna genome. the genomic rna is - kb in size and is capped and polyadenylated. three serologically distinct groups of coronaviruses have been described, with viruses in each group characterized by their host range and genome sequence. coronaviruses belong to a large family of viruses known to cause illnesses ranging from the common cold to more severe diseases, such as middle east respiratory syndrome (mers) and severe acute respiratory syndrome (sars). a novel coronavirus, sars-coronavirus- (sars-cov- ) was identified in december in wuhan, china, as a coronavirus that had not been previously identified in humans; this novel coronavirus is also known as the coronavirus disease . since its identification, sars-cov- has spread rapidly, affecting over countries and causing the / coronavirus pandemic. it was declared as a public health emergency of international concern on january by the world health organization (who). to date, many countries and regions have implemented lockdown measures and strict social distancing to limit the propagation of the virus. from a strategic and healthcare management perspective, the propagation pattern of the disease and the prediction of its spread over time is of great importance, which can save lives and minimize the social and economic consequences. epidemiological modeling is a powerful tool that can help understand disease spread, control, and prevention. different mathematical epidemic models have been used in the literature, including statistical models [ ] , mathematical models [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] , and network-based models [ ] [ ] [ ] . mathematical epidemic models are used to predict the course of an epidemic and develop methods for controlling it by comparing different possible scenarios based on the observed data. one of the widely used models is the susceptible-infected-recovered (sir) model [ , ] , where individuals are assigned into three compartments, i.e., susceptible (s), infected (i), and recovered (r). each individual belongs to one compartment and changes his/her state over time. an individual can transition from susceptible to infected with a specific infection rate. each individual can also transition from infected to recovered according to a specific recovery rate. this simple epidemic model works well for a homogeneous population that exhibits similar contact patterns, with contact probabilities between any two individuals considered to be equal. however, recent research has shown that the contact patterns in a real population are heterogeneous [ ] . as bidirectional social contacts are key factors in disease spreading, modeling epidemics on contact networks has been increasingly used to understand disease transmission and evaluate the impact of potential disease control [ ] [ ] [ ] . this is because contact relationships between individuals that allow infection propagation naturally define a network. hence, understanding the contact network structure can improve the predictions of the infection distribution among individuals and allow the simulation of the full epidemic dynamics. networks allow the modeling and simulation of disease control measures by manipulating the connections among different individuals. in this work, we propose a simulation model for the spread of covid- in saudi arabia using a network-based sir epidemic model. we first generated a contact network that captured the realistic social behaviors and dynamics of individuals in the population of saudi arabia. we aimed to match the model simulations with empirical data and then used the model to evaluate the effectiveness of the control measures employed by the saudi government, to predict the future dynamics of the disease in saudi arabia according to different scenarios, and to predict the percentage of individuals that must be vaccinated to stop the outbreak (when a vaccine becomes available). modeling the spread of covid- in saudi arabia has been discussed in the literature [ ] [ ] [ ] [ ] ; however, no studies used a network-based model that captured the social and dynamic properties that are intrinsic to saudi society. further, control measures, such as school closures, mosque closures, domestic flight shutdowns, and curfews, were not considered. the proposed model is used to explain how social measures, such as social distancing and regional lockdowns, influence the model parameters, which, in turn, change the number of infected cases over time. the proposed model considers the dynamic nature of individual contact behaviors and the variations in susceptibility and infectivity between individuals. the main contributions of the work can be summarized as follows: we built a model for contact networks that captures the social properties and dynamics intrinsic to saudi arabia's society. a set of attributes was defined for each node (representing each individual), including age, gender, nationality, and location. this is important as network structure and node attributes are crucial factors in the covid- epidemic spreading process. we built a network simulation model of the spread of covid- in saudi arabia using the widely adopted sir model. using our network simulations, we analyzed the processes by which covid- spreads. . we analyzed the effectiveness of the response of saudi authorities using our network simulations. . we predicted the future dynamics of the disease in saudi arabia under different scenarios. . we investigated the effectiveness of different vaccination strategies. in this work, we evaluated the effectiveness of saudi arabia's control measures on the epidemic dynamics. our results showed that strict local control measures, such as school closures, mosque closures, and flight shutdowns, play an important role in controlling the spread of the disease. in particular, mosque closures have the greatest impact on decreasing the transmission rate of the disease. our key results are in agreement with previous findings in china [ , , ] and in the united states [ ] . our model suggests that saudi arabia would have faced the peak of the outbreak on april with a total of about million infections if it had not imposed the control measures. this illustrates the importance of employing strict measures for flattening the epidemic curve of the infection and reducing the size of the epidemic. the strict social measures delay the peak of infection and minimize its period. altogether, these effects limit the burden on the healthcare system and prevent it from being overwhelmed. we also predicted the future dynamics of the outbreak in saudi arabia for the upcoming six months using multiple scenarios. according to the current data, the proposed model suggested that the peak would be roughly at the beginning of july, reaching a peak of . % of the population if people did not practice strict social distancing. the peak represents the highest number of daily infections. using our simulations, we also computed the percentage of people that must be vaccinated to stop the epidemic. our results suggest that the outbreak can be contained by increasing the percentage of the vaccinated population (but without resorting to mass vaccination of the population). according to our results, the proposed simulation model provides insights that reflect the dynamic behavior of covid- under different scenarios. the results can guide the local healthcare system for making decisions during the critical periods of the epidemic. the rest of the paper is organized as follows. in section , we discuss related literature works, and, in section , we describe the method, including the contact network generation model, the data, and the network simulation model. in sections and , we present and discuss the simulation results. finally, section concludes the work. the epidemic progression of covid- has received increased attention from the research community since its outbreak in late . the importance of understanding the virus transmission dynamics and further predicting the epidemic curve for public policy healthcare control measures has prompted multiple modeling efforts to control the outbreak [ , ] . existing contributions in the epidemiological modeling of covid- include different types of models, such as statistical models [ ] , mathematical models [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] , network-based models [ ] [ ] [ ] , and phenomenological models [ ] . due to their conceptual and mathematical simplicity, mathematical models, especially sir compartmental models, have long been popular in modeling epidemic dynamics [ , ]. an sir model describes the spread of a disease in a population, where individuals are assigned into three compartments: susceptible (s), infected (i), and recovered (r) [ , ] . however, previous studies [ ] reported that compartmental models lack explicit modeling of contact structures among individuals, which play a crucial role in understanding and modeling the dynamics of the spread of directly transmissible diseases. compartmental models assume homogenous mixing, where all individuals are equally likely to encounter infection, which may not reflect reality [ ] [ ] [ ] . manzo [ ] argued that a major problem with these kinds of compartmental models is that they can only be used with population-wide interventions because they do not model the topology of realistic social interactions. for these reasons, network-based models have been considered as an alternative for the epidemiological modeling of directly transmissible diseases [ ] [ ] [ ] . in such models, an infection may only spread over an arc between two nodes (or individuals) in the network that represents a contact. in the literature, several studies have addressed the deficiencies of previous compartmental models by extending sir-type models on a generated contact network [ ] . for instance, salathe and jones [ ] adopted this approach to study the effect of community structure on the epidemic dynamics of infectious disease and immunization intervention. volz [ ] modeled sir dynamics on a static random network, which represents the population structure of susceptible and infected individuals and their contact patterns with an arbitrary degree distribution. the authors extended their work in [ ] to cover a dynamic random network because contact patterns are inherently dynamic such that individuals tend to make and break relationships over time. miller et al. [ ] proposed an edge-based compartmental model, which unlike compartmental models, assumes a heterogeneous contact rate and considers the partnership duration. read and keeling [ ] investigated how local or global transmission routes in a contact network may affect the evolutionary selection of the transmission rate and infectious period, which determines the transmission dynamics of infectious diseases. ball et al. [ ] proposed a stochastic sir network epidemic model with preventive dropping, where a susceptible individual can practice social distancing by removing its edge to an infectious individual. due to the importance of social mixing patterns on modeling epidemic dynamics and evaluating the employed control measures, many research efforts have been made to estimate the patterns in different countries [ ] [ ] [ ] [ ] . despite the success of network-based models, several published studies on covid- modeling, including those supporting policy decision making, have focused on compartmental models [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] ] . manzo [ ] urged researchers to direct their efforts toward network-based sir models and to start discussing a large-scale collection of empirical network data to foster such models. ferguson et al. [ ] used a network-based model to study the impact of non-pharmaceutical interventions on reducing the spread of covid- to advise policymaking in the uk and other countries. the authors adopted an individual-based simulation model published in [ , ] , where spatial details were included, such as the household, school, workplace, and the wider community. the authors used real data to define multiple attributes of the model, including age and household distribution size, average class sizes, staff-student ratios, and workplace size. peirlinck et al. [ ] evaluated the effectiveness of intervention strategies and predicted the outbreak peak in china and the us. the authors modeled the covid- outbreak dynamics by combining a network model, where the nodes represent states and the edges represent connections between them, and an epidemic susceptible (s), infected (i), exposed (e), and recovered (seir) model. in their study, liu et al. [ ] developed a contact network and a model without contact to simulate the unfortunate incident of the covid- outbreak in the diamond princess cruise ship in two stages. the first stage was unprotected contact and the second stage was divided into two scenarios: protected contact and airborne spread of the virus. the authors designed a small-world network-based chain-binomial model [ , ] for the unprotected contact stage, a contact network epidemic model for protected contact for the crew stage, and a no-contact susceptible and infected model (ncsi) for the airborne spread for the passenger stage. they used bayesian inference and metropolis-hastings sampling to estimate the model parameters. several existing contributions modeled the covid- outbreak in saudi arabia using different models [ ] [ ] [ ] [ ] . for instance, alboaneen et al. [ ] predicted that saudi arabia would have a maximum total cases of , using logistic growth and sir models. in [ ] , alharbi et al. found that the sir model provided the best fit to the data compared to the generalized logistic, richards, and gompertz models. their results predicted that the total number of infected cases would reach , and that the pandemic would end by early september . aletreby et al. [ ] predicted that the pandemic would peak by the end of july . further, the work in [ ] used the sir model to predict future trends and compare the impact of control measures taken by saudi arabia and the united kingdom on the outcomes of covid- pandemic. their results indicated that early extreme measures imposed by the saudi authority played a major role in reducing the spread of the disease, compared to the uk. although there are some contributions that discussed covid- in saudi arabia [ ] [ ] [ ] [ ] [ ] and others modeled the epidemic dynamics of the covid- outbreak in the country using different models, such as sir [ , , ] , seir [ ] , logistic growth [ ] , and generalized logistic, richards, and gompertz models [ ] , none have used a network-based model or considered the social properties and dynamics intrinsic to saudi arabia's society. control measures, such as school closures, mosque closures, domestic flight shutdowns, and curfews, were not considered. this work seeks to fill that gap by investigating the spread of covid- in saudi arabia using a network-based epidemic simulation model. the first positive covid- case in saudi arabia was confirmed on march with more cases sporadically appearing in the following few weeks [ ] [ ] [ ] . according to the saudi ministry of health [ ] , the vast majority of infected people were home-comers from high-risk regions and their immediate contacts [ , , ]. the proposed simulation is a stochastic discrete network-based model that explicitly represents individuals and their interactions. first, we created a synthetic contact network that matches the essential structural properties of saudi arabia's society. the synthetic population was constructed to statistically match the population demographics of saudi arabia. secondly, we modeled the spread of covid- in saudi arabia using a classic sir model. finally, we conducted the contact network generation, simulation, and all analyses using the python-based networkx library [ ] . the generated network dataset, model parameters, and population demographics data are all available at https://github.com/halrashe/covid- _sa_simulation. to simulate the spread of covid- in saudi arabia, we generated a contact network using the intrinsic properties and dynamics of saudi arabia's society. we preserved the saudi-related demographics and social features that are essential for the transmission of infection. therefore, our network generation model captures key individual and social aspects. first, the network captures the properties of individuals by assigning a set of attributes to each node, including age group, gender, citizenship, and location. secondly, the network conforms to several observed contact behaviors among individuals such as location and age assortativity [ ] . we used data from the saudi general authority for statistics [ ] to assign the distribution of individuals for each attribute [ , ] (see figure a and table a in the appendix). this is computationally challenging [ , ] ; therefore, a contact network with a population of n = , individuals was generated with given age group, gender, citizenship, and location distributions. the geographic locations used to construct the network corresponded to the main administrative regions in saudi arabia. node connections represent contacts that may take place before and during the period of the epidemic. three connection types between node pairs were used in the network: familial, social, and random. see figure for a schematic of the network. we define our undirected and unweighted contact network g = (v,e), where v represents the set of individuals in the population and e represents the contact relationships between them. in the contact network g, each individual belongs to a household and the household sizes correspond to the values for saudi arabia reported in [ ] . each household is represented as a complete graph in which every node is connected to every other node by a familial edge. nodes from two different households can be linked in two ways, i.e., based on similarity (social edges) or at random (random edges). nodes are linked with social edges with a probability proportional to their similarity (i.e., a higher node similarity implies a higher chance of connection in the contact network). two nodes are considered similar when they exhibit similar attributes. the similarity of two nodes u and v, denoted as similarity (u,v) , is computed using the scaled euclidean distance between the two node vectors based on their attributes. let u and v be the vectors corresponding to nodes u and v. we first construct the vectors of the two nodes (the vector length is equal to the number of attributes describing each node, which is in this case). the corresponding elements in both vectors have values of and , respectively, if the two nodes have a different value for an attribute. otherwise, the corresponding elements of the two vectors have a value of . then, the similarity is computed as follows: where a and c are constants such that a + c = and c >> a. the goal here is to assign the location attribute a larger weight because it plays the most important role in deciding the contact relationship among node pairs. if two nodes are not similar, then they may be connected randomly with a probability of p + loc if they both belong to the same location and with a probability of p + random if they belong to different locations (p + random << p + loc). each edge eu,v connecting node u and v has a type attribute describing its formation. here, we use three edge types. the first one is familial when the two nodes u and v belong to the same household. the second is social when eu,v is formed as a result of the similarity between u and v. the third one is random when eu,v is formed completely at random. social edges represent contact relationships as a result of sharing school, work, interests, and neighborhoods. random edges represent contact relationships that occur as a result of coming into contact with another individual in a public place, a taxi, an airport, etc., or due to social contact that is not based on similarity. to make the model more realistic, a set of random edges is removed from the network (for example, not all familial relationships resemble infection-leading forms of contact) based on the edge type. a familial edge is removed with a probability of p − familial, a social edge is removed with a probability of p − social, and a random edge is removed with a probability of p − random such that p − familial << p − social << p − random. algorithm shows the contact network generation algorithm. figure shows the main properties of the contact network used in the simulation. nodes are linked with social edges with a probability proportional to their similarity (i.e., a higher node similarity implies a higher chance of connection in the contact network). two nodes are considered similar when they exhibit similar attributes. the similarity of two nodes u and v, denoted as similarity(u,v), is computed using the scaled euclidean distance between the two node vectors based on their attributes. let u and v be the vectors corresponding to nodes u and v. we first construct the vectors of the two nodes (the vector length is equal to the number of attributes describing each node, which is in this case). the corresponding elements in both vectors have values of and , respectively, if the two nodes have a different value for an attribute. otherwise, the corresponding elements of the two vectors have a value of . then, the similarity is computed as follows: where a and c are constants such that a + c = and c >> a. the goal here is to assign the location attribute a larger weight because it plays the most important role in deciding the contact relationship among node pairs. if two nodes are not similar, then they may be connected randomly with a probability of p + loc if they both belong to the same location and with a probability of p + random if they belong to different locations (p + random << p + loc ). each edge e u,v connecting node u and v has a type attribute describing its formation. here, we use three edge types. the first one is familial when the two nodes u and v belong to the same household. the second is social when e u,v is formed as a result of the similarity between u and v. the third one is random when e u,v is formed completely at random. social edges represent contact relationships as a result of sharing school, work, interests, and neighborhoods. random edges represent contact relationships that occur as a result of coming into contact with another individual in a public place, a taxi, an airport, etc., or due to social contact that is not based on similarity. to make the model more realistic, a set of random edges is removed from the network (for example, not all familial relationships resemble infection-leading forms of contact) based on the edge type. a familial edge is removed with a probability of p − familial , a social edge is removed with a probability of p − social , and a random edge is removed with a probability of p − random such that p − familial << p − social << p − random . algorithm shows the contact network generation algorithm. figure shows the main properties of the contact network used in the simulation. algorithm contact network generation : create household clusters (complete graphs) with given average sizes : type(e uv ) ← f amilial ∀ e uv ∈ e : for each pair of non-neighboring nodes u, v do : if similarity(u, v) > t then {t is the node pairs similarity threshold} : e ← e ∪ e uv with probability p + social : type(e uv ) ← social : else : if location(u) = location(v) then : e ← e ∪ e uv with probability p + loc : type(e uv ) ← random : else : e ← e ∪ e uv with probability p + if type(e uv ) = social then : e ← e − e uv with probability p − social : each of the square-shaped regions in the similarity matrix in figure b is formed because of the citizenship attribute. the bottom-left region corresponds to saudi individuals and the other two correspond to non-saudi individuals. non-saudi individuals are partitioned into two groups because two patterns of contact have been identified between non-saudi individuals. due to the model's stochasticity, similarity alone does not control edge formation (see the adjacency matrix in figure b . table lists the structural properties of the underlying contact graph, which may have a significant impact on the dynamics of the disease [ ] . the network density is zero for a network with no edges and for a network with all possible edges. our contact network had a density of . , revealing that it is a sparse network with every node connected to every other node (number of connected components is one). the node degree is the number of contacts an individual node has, which provides a quantitative measure of the node's role in the disease transmission process (figure c ). the maximum degree shows the most active node (or nodes) in the network, representing individuals contacting a large number of people, such as sales workers and delivery and taxi drivers in highly populated locations (e.g., riyadh). in addition, the network exhibits a small-world property with a high clustering coefficient and a short average path length and diameter. the network also shows a strong community structure. the modularity value [ ] ranges between − and and is used to measure the quality of communities (higher modularity indicates stronger community structure). our contact network had communities, each of which corresponded to a location (this is expected from the generation model used to create the network). generally, our contact network structure matches the properties of other contact networks [ , , ] . however, unlike other contact network generation models, we did not assume any network properties in advance [ , [ ] [ ] [ ] . each of the square-shaped regions in the similarity matrix in figure (b) is formed because of the citizenship attribute. the bottom-left region corresponds to saudi individuals and the other two correspond to non-saudi individuals. non-saudi individuals are partitioned into two groups because two patterns of contact have been identified between non-saudi individuals. due to the model's stochasticity, similarity alone does not control edge formation (see the adjacency matrix in figure (b). table lists the structural properties of the underlying contact graph, which may have a significant impact on the dynamics of the disease [ ] . the network density is zero for a network with no edges and for a network with all possible edges. our contact network had a density of . , revealing that it is a sparse network with every node connected to every other node (number of connected components is one). table . contact network properties. definition value the transmission dynamics of covid- depend on the structure of the underlying contact network and individual susceptibilities. the susceptibility defines how likely an individual is to become infected if he or she comes into contact with an infected individual. since it is unknown what attributes of an individual determine his or her susceptibility, we used statistical tests on a real covid- patient dataset to identify them. to this end, we requested and received data about the patients in saudi arabia from the saudi ministry of health. the data consist of records of all individuals who were tested by taking nasopharyngeal swabs for covid- in saudi arabia between march until april . several data cleaning steps were applied to the dataset before testing. the characteristics of the final dataset are shown in figure a and table a in the appendix. as can be seen in table a , the dataset is unbalanced because the majority of the cases are negative. therefore, we conducted oversampling for the positive class according to the synthetic minority over-sampling technique (smote) using python [ ] . we then applied the pearson's chi-square statistical hypothesis test to both the original unbalanced dataset and the balanced dataset. chi-square was used to assess whether there was a significant statistical relationship between the attribute (i.e., age, gender, citizenship, and location; the independent variables) and the test result (the dependent variable). this is a well-known feature selection technique in machine learning [ ] . our goal is to determine which attribute contribute to an individual's susceptibility. the resulting p-values for the attributes are presented in table . it can be seen that all p-values were < . , which implies a significant relationship. therefore, all attributes were included to estimate an individual's susceptibility. let g = (v,e) denote the contact network defined in section . . to simulate the spread of covid- in saudi arabia, we ran a standard sir epidemic model on our contact network. according to this model, each node u has a state state(u) that is either susceptible, infected, or recovered (immune). transitions are only allowed from susceptible to infected or from infected to recovered. the sir model is a reasonable representation for covid- , which assumes (up to this point) to lead to full immunity after recovery [ ] . the epidemiology of covid- and its clinical characteristics are not fully known. therefore, we heavily relied on recently available data [ , ] for disease transmission. based on the analysis in section . , we identified four main attributes that play a role in the transmission of infection: age, gender, citizenship, and location. accordingly, each node u was assigned a susceptibility value susceptibility(u) describing its risk of infection. the transmission probability from an infected node v to a susceptible node u occurs with a probability proportional to the susceptibility of node u.; i.e., p u,v = susceptibility(u), where state(v) = infected. to find each susceptibility value, we extracted all possible events (attribute value combinations) from the available records and calculated the probability of each compound event. figure a and table a list the node susceptibility values. initially (at time ), the population is fully susceptible with a single infected individual. the infected individual was chosen to have the same attributes (i.e., age group, gender, citizenship, and location) as the first recorded case in saudi arabia (a -year-old male from the eastern region). thereafter, the infection progresses via the contact network for several iterations (each iteration corresponds to one day). the incubation period was set to days, which is the maximum incubation period recorded for covid- [ ] . the recovery rate was set to . (see table ). the major control measures employed by the saudi government were implemented in the model, which include school closures, mosque closures, domestic flight shutdowns, and in-home curfews. the model also implements social distancing, ground screening, partial business reopening, and business as usual. the major control measures, their dates, and assumed compliance rates used in the model are listed in table . in some cases, control measures are not enough to prevent contact; for example, school friends can meet outside of school, and people can still travel by car to meet. in table , a compliance rate of % for ground screening represents the percentage of people who were infected but only detected as a result of the ground screening. business as usual refers to the full reopening of businesses, where we assume that contact relationships are restored and social distancing is the only measure that affects the susceptibility of individuals. the compliance rates that produced simulation curves closest to the actual curve were selected. control measures were introduced by removing edges between relevant nodes and with a specific compliance rate. for example, school closures resulted in removing edges among node pairs who shared the same location and age group. edges were removed with a specific probability and among a specific percentage of relevant nodes. on the other hand, partial business reopening and business as usual result in adding removed edges between a given set of nodes and with a given probability. finally, we implemented social distancing as a reduction in the probability of infection (decreasing node susceptibility). to establish the simulation model parameters, we used the empirical data of confirmed cases of covid- in saudi arabia for the period from march (first confirmed case) until may . the model parameters are listed in table . we compare the actual and simulated results of the daily and cumulative new infected cases in figures and , respectively. note that all simulation results corresponded to averages of simulations and were scaled to the actual number of infected cases. it can be seen from the figures that our model fit the reported data well. to further confirm the fit of our model, we predicted the daily cases for the period from may to june and compared it with the available actual data (see figure ). all regulations imposed after may are not implemented in the model, which may explain the overestimations of the simulated curve around may. the values of the mean absolute percentage error (mape) and the symmetric mean absolute percentage error (smape) for the prediction were . % and . %, respectively. outlier values were removed due to the extreme sensitivity of the above error measures to outliers [ , ] . the values of mape and smape before removing the outliers were . % and . %, respectively. we further simulated and analyzed the effect of the selected saudi control measures and their timings. then, we predicted the disease dynamics and measured the effect of vaccination. it can be seen from the figures that our model fit the reported data well. to further confirm the fit of our model, we predicted the daily cases for the period from may to june and compared it with the available actual data (see figure ). all regulations imposed after may are not implemented in the model, which may explain the overestimations of the simulated curve around may. the values of the mean absolute percentage error (mape) and the symmetric mean absolute percentage error (smape) for the prediction were . % and . %, respectively. outlier values were removed due to the extreme sensitivity of the above error measures to outliers [ , ] . the values of mape and smape before removing the outliers were . % and . %, respectively. it can be seen from the figures that our model fit the reported data well. to further confirm the fit of our model, we predicted the daily cases for the period from may to june and compared it with the available actual data (see figure ). all regulations imposed after may are not implemented in the model, which may explain the overestimations of the simulated curve around may. the values of the mean absolute percentage error (mape) and the symmetric mean absolute percentage error (smape) for the prediction were . % and . %, respectively. outlier values were removed due to the extreme sensitivity of the above error measures to outliers [ , ] . the values of mape and smape before removing the outliers were . % and . %, respectively. it can be seen from the figures that our model fit the reported data well. to further confirm the fit of our model, we predicted the daily cases for the period from may to june and compared it with the available actual data (see figure ). all regulations imposed after may are not implemented in the model, which may explain the overestimations of the simulated curve around may. the values of the mean absolute percentage error (mape) and the symmetric mean absolute percentage error (smape) for the prediction were . % and . %, respectively. outlier values were removed due to the extreme sensitivity of the above error measures to outliers [ , ] . the values of mape and smape before removing the outliers were . % and . %, respectively. we further simulated and analyzed the effect of the selected saudi control measures and their timings. then, we predicted the disease dynamics and measured the effect of vaccination. we further simulated and analyzed the effect of the selected saudi control measures and their timings. then, we predicted the disease dynamics and measured the effect of vaccination. to determine the efficacy of the imposed control measures in saudi arabia, we simulated the epidemic without each measure individually for the period from march to may . then, we compared the resulting simulation curve with the original epidemic curve. the results of this analysis provided an estimate of the number of new cases that were prevented using the control measure. figure illustrates the epidemic curves produced from not implementing the major control measures (i.e., school closures, mosque closures, domestic flight shutdowns, and curfews) imposed by the saudi government. to determine the efficacy of the imposed control measures in saudi arabia, we simulated the epidemic without each measure individually for the period from march to may . then, we compared the resulting simulation curve with the original epidemic curve. the results of this analysis provided an estimate of the number of new cases that were prevented using the control measure. figure illustrates the epidemic curves produced from not implementing the major control measures (i.e., school closures, mosque closures, domestic flight shutdowns, and curfews) imposed by the saudi government. the figure shows that removing any of the control measures caused the epidemic curve to reach the peak earlier compared to the actual curve. when the school closures measure is not implemented, the maximum percentage increase in the number of daily cases was % and the curve peak occurred earlier compared to the other curves. not implementing mosque closures and curfews also caused the curve to peak early compared to the actual curve. cancelling mosque closures caused % maximum percentage increase, while cancelling curfews caused only % increase. cancelling flight shutdowns resulted in % maximum percentage increase in the number of daily cases. to assess the impact of the selected date of each of the control measures, we simulated the epidemic with a late effective date for each measure. the results are shown in figure the figure shows that removing any of the control measures caused the epidemic curve to reach the peak earlier compared to the actual curve. when the school closures measure is not implemented, the maximum percentage increase in the number of daily cases was % and the curve peak occurred earlier compared to the other curves. not implementing mosque closures and curfews also caused the curve to peak early compared to the actual curve. cancelling mosque closures caused % maximum percentage increase, while cancelling curfews caused only % increase. cancelling flight shutdowns resulted in % maximum percentage increase in the number of daily cases. to assess the impact of the selected date of each of the control measures, we simulated the epidemic with a late effective date for each measure. the results are shown in figure , where figure a shows the impact of delaying school closures, figure b shows the impact of delaying mosque closures, figure c shows the impact of delaying domestic flight shutdowns, figure d shows the impact of delaying curfews, and figure e shows the actual curve (for ease of comparison). each figure also shows the percentage increase in the infection rate and the total number of infected cases when the corresponding control measure was delayed. the figure shows that delaying any of the control measures caused an increase in the infection rate and in the total number of infected cases. when the mosque closures measure was delayed, the total number of infected cases increased by % and the infection rate increased by %. delaying curfews caused % increase in the total number of infected cases and % increase in the infection rate. when school closures or flight shutdowns were delayed, the infection rate increased by % and %, respectively. delaying school closures and flight shutdowns increased the total number of infected cases by % and %, respectively. we used the proposed model to predict the future dynamics of the outbreak in saudi arabia for the upcoming period of six months (from may to december) with respect to three scenarios, representing multiple levels of adherence to the social distancing recommendations after may (the announced business as usual date). figure shows the number of infected individuals per day for all scenarios. in particular, figure (a)-(c) show the epidemic dynamics with poor ( % of population), moderate ( % of population), and strong ( % of population) compliance to social distancing, respectively. the level of adherence is defined by the percentage of people that practice social distancing. for comparison purposes, we also predicted the dynamics of the outbreak when no control measures or social distancing were imposed during the whole pandemic period starting from march. the red curve in figure shows that if no control measures were imposed, the peak of the infection was predicted to be about . % on april with a total outbreak size of % of the population (the peak refers to the highest number of daily infections) and the epidemic ended at the end of august . the figure shows that delaying any of the control measures caused an increase in the infection rate and in the total number of infected cases. when the mosque closures measure was delayed, the total number of infected cases increased by % and the infection rate increased by %. delaying curfews caused % increase in the total number of infected cases and % increase in the infection rate. when school closures or flight shutdowns were delayed, the infection rate increased by % and %, respectively. delaying school closures and flight shutdowns increased the total number of infected cases by % and %, respectively. we used the proposed model to predict the future dynamics of the outbreak in saudi arabia for the upcoming period of six months (from may to december) with respect to three scenarios, representing multiple levels of adherence to the social distancing recommendations after may (the announced business as usual date). figure shows the number of infected individuals per day for all scenarios. in particular, figure a -c show the epidemic dynamics with poor ( % of population), moderate ( % of population), and strong ( % of population) compliance to social distancing, respectively. the level of adherence is defined by the percentage of people that practice social distancing. for comparison purposes, we also predicted the dynamics of the outbreak when no control measures or social distancing were imposed during the whole pandemic period starting from march. the red curve in figure shows that if no control measures were imposed, the peak of the infection was predicted to be about . % on april with a total outbreak size of % of the population (the peak refers to the highest number of daily infections) and the epidemic ended at the end of august . population is practicing social distancing) after business return on may . the simulation results suggest that there would be two peaks at roughly the beginning of july and the middle of august. the peak of the infection will be . % with a total outbreak size of about % of the population. according to this scenario, our model suggests that the epidemic will end at the beginning of november with over million infected individuals, which is measured according to the number of active cases (i.e., when the number of active cases is close to zero). the epidemic curve in figure (b) shows the disease dynamics when social distancing is practiced moderately (about % of the population practicing social distancing). the figure suggests that the first peak will remain below . %, the second peak will be avoided, and the total number of infected individuals will be about % of the population. in figure (c), the epidemic curve suggests that when most people practice social distancing ( % of the population), the total number of infected individuals will decrease to about %. we next explored the dynamics of the epidemic if part of the population is vaccinated. this is helpful to understand what percentage of the population must be vaccinated to stop the epidemic. we considered four scenarios where %, %, %, and % of the population was vaccinated. in the proposed model, vaccination is represented by removing the edges between a node u and part of its neighbor nodes. we show the epidemic curves and the results of multiple vaccination scenarios in figure and table , respectively. we assumed that a vaccine would become available on june figure a shows the disease dynamics when social distancing adherence is poor ( % of the population is practicing social distancing) after business return on may . the simulation results suggest that there would be two peaks at roughly the beginning of july and the middle of august. the peak of the infection will be . % with a total outbreak size of about % of the population. according to this scenario, our model suggests that the epidemic will end at the beginning of november with over million infected individuals, which is measured according to the number of active cases (i.e., when the number of active cases is close to zero). the epidemic curve in figure b shows the disease dynamics when social distancing is practiced moderately (about % of the population practicing social distancing). the figure suggests that the first peak will remain below . %, the second peak will be avoided, and the total number of infected individuals will be about % of the population. in figure c , the epidemic curve suggests that when most people practice social distancing ( % of the population), the total number of infected individuals will decrease to about %. we next explored the dynamics of the epidemic if part of the population is vaccinated. this is helpful to understand what percentage of the population must be vaccinated to stop the epidemic. we considered four scenarios where %, %, %, and % of the population was vaccinated. in the proposed model, vaccination is represented by removing the edges between a node u and part of its neighbor nodes. we show the epidemic curves and the results of multiple vaccination scenarios in figure and table , respectively. we assumed that a vaccine would become available on june (the date was chosen to make the differences easily visible on the plot). before this date, all control measures are imposed with the compliance rates shown in table . however, irrespective of the dates, the insights available in this simulation are useful for whenever a vaccine becomes available. table . however, irrespective of the dates, the insights available in this simulation are useful for whenever a vaccine becomes available. figure . epidemic curves of multiple vaccination scenarios. curves are smoothed using a savitzky-golay filter [ ] (filter with a window length of and a degree polynomial). figure and table suggest that the outbreak and peak sizes are inversely proportional to the percentage of vaccinated population. further, we observe that the higher the percentage of population vaccinated is, the earlier the epidemic peaks and the epidemic ends. for example, when % of the population is vaccinated, the peak occurs on july and ends on november . when % of the population is vaccinated, the peak occurs on may and ends on june . the proposed network model allows the analysis and evaluation of various control measures that are used to slow or prevent the transmission of covid- in saudi arabia and to evaluate the timing of each measure. moreover, the model can be used to predict the future dynamics of the outbreak in saudi arabia with and without the availability of vaccination. the results presented in section . show the epidemic curves resulting from not implementing each of the four major control measures employed by the saudi government. the results reveal several important pieces of information. first, they suggest that all of the employed control measures played a significant role in delaying the peak of the epidemic, where the peak represents the highest number of daily infections. this can be seen by comparing the dashed vertical lines on the curves, which show the day at which the number of new cases reached the maximum peak (compared to the actual curve). secondly, it is apparent from the top curve in figure , that implementing school closures had the maximum impact because canceling school closures caused the curve to reach the peak early compared to the other three curves. thirdly, the results suggest that the employed measures also played an important role in slowing down the infection rate. for example, the maximum percentage increase in the number of cases in the original curve was %, whereas it was %, %, and % without implementing school closures, mosque closures, and flight shutdowns, respectively. our results are in agreement with previous findings in china [ , , ] and in the united states [ ] . for example, the authors in [ ] suggested that community mitigation actions such figure and table suggest that the outbreak and peak sizes are inversely proportional to the percentage of vaccinated population. further, we observe that the higher the percentage of population vaccinated is, the earlier the epidemic peaks and the epidemic ends. for example, when % of the population is vaccinated, the peak occurs on july and ends on november . when % of the population is vaccinated, the peak occurs on may and ends on june . the proposed network model allows the analysis and evaluation of various control measures that are used to slow or prevent the transmission of covid- in saudi arabia and to evaluate the timing of each measure. moreover, the model can be used to predict the future dynamics of the outbreak in saudi arabia with and without the availability of vaccination. the results presented in section . show the epidemic curves resulting from not implementing each of the four major control measures employed by the saudi government. the results reveal several important pieces of information. first, they suggest that all of the employed control measures played a significant role in delaying the peak of the epidemic, where the peak represents the highest number of daily infections. this can be seen by comparing the dashed vertical lines on the curves, which show the day at which the number of new cases reached the maximum peak (compared to the actual curve). secondly, it is apparent from the top curve in figure , that implementing school closures had the maximum impact because canceling school closures caused the curve to reach the peak early compared to the other three curves. thirdly, the results suggest that the employed measures also played an important role in slowing down the infection rate. for example, the maximum percentage increase in the number of cases in the original curve was %, whereas it was %, %, and % without implementing school closures, mosque closures, and flight shutdowns, respectively. our results are in agreement with previous findings in china [ , , ] and in the united states [ ] . for example, the authors in [ ] suggested that community mitigation actions such as isolation of infectious individuals, quarantine of close contacts, and travel restrictions impact the covid- disease infection rates. canceling curfews appeared to have a minimum impact on slowing down the infection rate compared to other measures as it only caused a % increase in the number of cases (red curve in figure ). this is likely because the assumed compliance rate for this measure was only % (see table ), which is the lowest compared to those of other measures. the time at which the control measures are implemented against the epidemic is critical. in section . , we presented the epidemic curves after changing the effective date of each of the employed control measures. from the results, it can be observed that delaying one of the measures increased the total number of infected cases compared to when all measures were implemented (the actual curve). for instance, when the effective date of the school closure control measure was delayed by days, the total number of infected cases increased by %. however, the highest increase in the number of infected cases was seen when mosque closures and curfews were delayed ( % and %, respectively). similar trends can be observed with respect to the infection rate as delaying mosque closures and curfew implementation caused maximum percentage increases ( % and %, respectively). this can be explained by the susceptibility of the nodes affected by each control measure. for example, mosque closures mainly affect contact relationships (edges) among adult males. generally, the node susceptibilities of adult male individuals are higher compared to those of other nodes (table a and section . ). delaying flight shutdowns had the least impact on the total number of infected cases ( % increase compared to the actual). this can be explained by the low number of edges that connect individuals from different locations (figure (d) ). the model was used to predict the future dynamics of covid- in saudi arabia for the upcoming period of six months with and without control measures. the results are shown in section . . a number of observations can be made from the results. first, the size of the peak when no control measures were imposed would be disastrous as it would result in a total of over million infected individuals, which would overwhelm the healthcare system. we next compare the three scenarios when control measures are imposed. first, if social distancing adherence is poor, the two peaks, occurring at roughly the beginning of july and the middle of august, would result in over million infected individuals by the end of the epidemic (at the beginning of november ). this number is half of the number of infected individuals when no control measures were imposed. second, social distancing significantly decreased the infection peak and the total number of infections. our results contradict earlier findings [ , , , ] . for example, [ ] predicted that the % pandemic end in saudi arabia should have been on may . in [ ] , the authors predicted that the final phase of the outbreak would occur by the end of june with a total of , infected individuals. further, the work in [ ] predicted that pandemic would end by early september with a total of , infected individuals. in comparing the two scenarios (without control measures and with control measures), it is clear that employing different control measures is crucial for flattening the epidemic curve and reducing the final size of the epidemic. these measures also prolong the peak period and minimize the peak, which is crucial to avoid overwhelming the healthcare system. the model was used to predict the disease dynamics under multiple vaccination scenarios. the results (section . ) suggest that the epidemic will end in saudi arabia on november if no one in the population is vaccinated (i.e., if no vaccination is available). at this point, a sufficient amount of the population developed immunity to the disease because they previously had the virus and had recovered. however, the results showed that, in this scenario, around % of the population may become infected, which is equivalent to over million individuals, and the epidemic may reach its peak on july with over a hundred thousand individuals infected. in the best-case scenario, when % of the population is vaccinated on june the results suggested that it may take only days to end the epidemic with an outbreak size of %. this period increases by almost two months when only % of the population is vaccinated. when % of the population is vaccinated, the results show that the epidemic may end in late september. note that specific recommendations for vaccination may consider multiple factors analyzed in this section, such as the outbreak size, peak size, and pandemic end date, but may also consider other factors, such as the vaccination cost and the number of critical cases. the proposed network generation and simulation models are part of an effort to create an accurate simulation of the spread of covid- in saudi arabia. however, the findings in this work are subject to several limitations. as with all models, the quality of our model depends on the quality of the underlying data. this includes the contact patterns, data of infected cases, and pathogen data. inadequate and missing data were replaced with assumptions and simplifications. for example, in the proposed contact network generation model, the contact patterns and edge formation among individuals were simplified to three contact types with corresponding assumed probabilities. therefore, a greater focus on realistic contact patterns in saudi arabia using a social contact survey could produce interesting findings that could enhance the accuracy of our model. moreover, the contact network used to simulate the disease was static. a dynamic network, in which nodes and edges are added and removed over time due to birth, death, and quarantine, would be more realistic to represent contact relationships among individuals; this is left for future work. our predictions also include inherent uncertainty as the model parameters were derived from limited clinical data. for example, the node susceptibilities were based on limited data (records from march to april). in addition, the population's actual compliance to the recommended control measures is unknown. therefore, the compliance rates used in the model were assumed. more information on population compliance rates would help improve the accuracy of the model. the goal of this work was to model and analyze the spread of covid- in saudi arabia using a network-based epidemic model. first, we generated a realistic contact network of individuals in saudi arabia. then, we used the sir model to simulate the spread of covid- . the proposed model accounted for the dynamic nature of individual contact behaviors and the variations in susceptibility between individuals. the proposed simulation model was used to evaluate the effectiveness of the employed saudi control measures and their timings on the dynamics of the epidemic and to predict the future dynamics of the outbreak in saudi arabia. the model was also used to calculate the percentage of people that need to be vaccinated to stop the epidemic. funding: this research received no external funding. table b . distribution of nodes by age group, gender, citizenship, and location. the age distribution of individuals was based on citizenship and gender but is approximated here. similarly, the gender distribution was also based on citizenship but is approximated here. age group - % application of the arima model on the covid- epidemic dataset. data brief , modified seir and ai prediction of the epidemics trend of covid- in china under public health interventions a conceptual model for the coronavirus disease (covid- ) outbreak in wuhan, china with individual reaction and governmental action estimation of the transmission risk of the -ncov and its implication for public health interventions analysis and forecast of covid- spreading in china, italy and france transmission dynamics of the covid outbreak and effectiveness of government interventions: a data-driven analysis interrupting covid- transmission by implementing enhanced traffic control bundling: implications for global prevention and control efforts feasibility of controlling covid- outbreaks by isolation of cases and contacts modeling the epidemic dynamics and control of covid- outbreak in china effect of delay in diagnosis on transmission of covid- outbreak dynamics of covid- in china and the united states using the contact network model and metropolis-hastings sampling to reconstruct the covid- spread on the diamond princess impact of non-pharmaceutical interventions (npis) to reduce covid mortality and healthcare demand a contribution to the mathematical theory of epidemics infectious diseases of humans: dynamics and control complex social networks are missing in the dominant covid- epidemic models networks and epidemic models networks and the epidemiology of infectious disease epidemic spread in networks: existing methods and current challenges predicting the epidemiological outbreak of the coronavirus disease (covid- ) in saudi arabia epidemiological modeling of covid- in saudi arabia: spread projection, awareness, and impact of treatment dynamics of sars-cov- outbreak in the kingdom of saudi arabia: a predictive model covid- outcomes in saudi arabia and the uk: a tale of two kingdoms the effectiveness of quarantine of wuhan city against the corona virus disease (covid- ): a well-mixed seir model analysis the effect of human mobility and control measures on the covid- epidemic in china covid- : knowns, unknowns, and questions. msphere , sars-cov- and covid- : the most important research questions real-time forecasts of the covid- epidemic in china from contact network epidemiology: bond percolation applied to infectious disease prediction and control edge-based compartmental modeling for infectious disease spread when individual behaviour matters: homogeneous and network models in epidemiology network theory and sars: predicting outbreak diversity modeling individual vulnerability to communicable diseases: a framework and design dynamics and control of diseases in networks with community structure sir dynamics in random networks with heterogeneous connectivity reality mining: sensing complex social systems disease evolution on networks: the role of contact structure a stochastic sir network epidemic model with preventive dropping of edges social contacts and mixing patterns relevant to the spread of infectious diseases the effect of network mixing patterns on epidemic dynamics and the efficacy of disease contact tracing hens, n. a household-based study of contact networks relevant for the spread of infectious diseases in the highlands of peru estimating contact patterns relevant to the spread of infectious diseases in russia the effect of control strategies to reduce social mixing on outcomes of the covid- epidemic in wuhan, china: a modeling study strategies for mitigating an influenza pandemic modeling targeted layered containment of an influenza pandemic in the united states collective dynamics of small-world networks an examination of the reed-frost theory of epidemics the cancellation of mass gatherings (mgs)? decision making in the time of covid- covid- in the shadows of mers-cov in the kingdom of saudi arabia covid- -the role of mass gatherings covid- : preparing for superspreader potential among umrah pilgrims to saudi arabia saudi arabia's drastic measures to curb the covid- outbreak: temporary suspension of the umrah pilgrimage covid- ) disease interactive dashboard humanitarian data exchange-novel coronavirus (covid- ) cases data projecting social contact matrices in countries using contact surveys and demographic data population based on gender population distribution over the main administrative regions based on gender and nationality chains of affection: the structure of adolescent romantic and sexual networks family demographic transition in saudi arabia: emerging issues and concerns the structure and function of complex networks. siam rev finding and evaluating community structure in networks modeling disease outbreaks in realistic urban social networks an efficient immunization strategy for community networks susceptible-infected-recovered epidemics in dynamic contact networks generating realistic scaled complex networks synthetic minority over-sampling technique feature selection for classification: a review. data classif covid- and postinfection immunity: limited evidence, many remaining questions the incubation period of coronavirus disease (covid- ) from publicly reported confirmed cases: estimation and application a new accuracy measure based on bounded relative error for time series forecasting principles of forecasting: a handbook for researchers and practitioners smoothing and differentiation of data by simplified least squares procedures when will covid- end? data-driven prediction epidemic situation and forecasting of covid- in saudi arabia using the sir model key: cord- - gr lh w authors: khraif, rshood m.; salam, asharaf abdul; nair, p. s.; elsegaey, ibrahim title: migration in saudi arabia: present and prospects date: - - journal: india's low-skilled migration to the middle east doi: . / - - - - _ sha: doc_id: cord_uid: gr lh w as compared with other gulf cooperation council (gcc) countries, saudi arabia has distinct demographic features. this leads the saudi government to take measures to revisit its existing policies and schemes concerned with population. with this brief outline, migration data used in this article are pitched to understand five dimensions: ( ) to look at the saudi citizens’ migration trends within the kingdom, ( ) to analyse the impact of migration on the kingdom’s population growth and also on the neighbouring gcc countries, ( ) to look at the changes taking place annually in the kingdom’s migration trends and in the other gcc countries, ( ) to examine the migrants, looking at their origin place and ( ) to analyse the variation between immigrants and saudi arabia citizens in terms of demographic parameters like population growth, sex ratio, broad age groups and age-sex distribution. various databases available at both national and international levels were taken to address the five dimensions. the findings showed that push and pull factors and infrastructure differentials are taken into consideration while saudi population internally migrate. all the gcc countries, including saudi arabia, experience international migration streams subject to the labour requirements and governmental regulations for both arabs and non-arabs. immigrant demographics are characterized by saudi arabia’s labour demand controlled by adult males from other countries. ; khraif ) . labour force in the kingdom experiences structural changes, with service sector taking the lead in replacing the agricultural sector which perpetuated the heavy need for foreign labour (khraif ; sufian ; united nations ) . expatriate labour force, with their sincere involvement in daily responsibilities, created a total reliance even in private space-direct impact of non-nationals on the lives of citizens (forstenlechner and rutledge ) . migration is of wide concern among nations, especially in the gcc, although the migration load has declined with time (tabutin and schoumaker ) . the kingdom of saudi arabia has the largest land area and population among the gcc members, where expatriates form . per cent of the total population (center for population studies ). that is, one in every four persons in the kingdom is an expatriate, indirectly influencing fertility decisions (khraif a, b; courbage ) . the expert and technical labour force brought in to fulfil the increasing requirements of technological development and innovation affects the locally available native manpower in the fast changing saudi arabia, resulting in an imbalance on regional and urban scales, impacting upon economy, urban planning, transport, housing and employment and, in return, creating an over-urbanization (united nations khraif khraif , makki ). still, from the role played by migrants in the economy, provisions of government services and social contracts, citizens benefit from their unregulated cheap employment at domestic level (forstenlechner and rutledge ) . the labour and immigration policies are undergoing changes in the kingdom, expecting its outcome in the near future-absorption of native saudi youth into the labour force-and skill upgradation-educational, technical and professional. with this scenario, an analysis of migration data is made in this context in order to: ( ) look at the saudi citizens' migration trends within the kingdom; ( ) analyse the impact of migration on kingdom's population growth and also on the neighbouring gcc countries; ( ) look at the changes taking place annually in kingdom's migration trends and in the other gcc countries; ( ) examine the migrants by looking at the origin place; and ( ) analyse the variation between immigrants and saudi citizens in terms of demographic parameters. the saudi arabian national census has started publishing migration data by administrative area (place of birth and place of current residence) since , specifically for the native population. analyses were carried out to calculate the following: • in-migration rate = (number of persons entering an administrative area/population in the area) * . the international database of us census bureau provides migration data-net migrants by year, which has been collected for saudi arabia and the other gcc states from to -to compare the changes and its contribution to the population growth. individual country experiences on migration are plotted. further, the world bank bilateral migration database has been accessed online to trace the migration flow to the gcc states for three periods: , and . all these data were utilized to explain the migration process in the kingdom of saudi arabia. the findings of the analyses are presented under varying sections such as internal migration, international migration and differences between natives and migrants. the capital, al-riyadh, is vibrant in terms of not only population size but also migration flows (table . ). as against an in-migration rate of per , the out-migration rate is only per , showing high levels of attraction or in-migrant flows determined by the administrative requirements, educational and employment prospects and the quality of life. other areas having pull factors are tabouk (the military headquarters) and the eastern region (the industrial hub). makkah al-mokarramah also stands as attractive with high pull factors, whereas al-baha, jazan, hail, al-qaseem, aseer and the northern borders exhibit pushing power. neither the urban infrastructure in al-baha (al-baha, beljarshy), jazan (sbia and abu arish), hail (hail and baqaa), aseer (khamis mushayt and abha) and northern borders (arar and rafha) nor the major governorates in these administrative areas are able to retain the native labour force. makkah al-mokarramah maintains the status without being influenced significantly by the migration flows. madina al-monawarah, the pilgrim location, also records an out-migration, which might explain the decreasing demand for or interest of natives to serve the pilgrims. the replacement of currently existing expatriate health-care staff by the local nationals-untapped women resources-is imperative to meet the complex health needs and rising public health issues (maben et al. ). but the current trend of out-migration from the makkah al-mokarramah leads to positive net migration. promoting local-level human resources development shall help in bringing a workable link between the three tiers of health-care delivery through referral system and continuing medical education ensuring population health (al-yousuf et al. ) . the increasing administrative jobs and industrial job market influence the internal migration in the kingdom, which has reasons other than employment, such as residential mobility-buying or building homes, increase in family size, affordability for better dwelling, rental rates, evacuation by the owner or inadequate services substantiate the migrants' relation with house ownership (helderman et al. ) . however, majority of internal movements are from rural to urban in nature, accelerating the urbanization process, as stated by clarke and murray ( ) , with a successful spatial distribution policy that reduces widespread regional disparity in physical and social infrastructure and uneven settlements scattered at long distances (al-khalifeh ; makki ) . migration intentions to continue living in a city are determined by the years lived in the city, home ownership in the city, parents' place of residence, land ownership in the village and area of origin (khraif ; ) . areas with higher levels of out-migration require increased levels of employment potential in the destinations in both public and private sectors. on the other hand, those areas experiencing substantial levels of inmigration require redistribution policies, both for population and infrastructure development programmes. according to the recent international strategies on industrial location, the production and manufacturing units are relocated to land areas not used hitherto, which currently paves way for a return migration. saudi arabia's efforts in these lines shall create prospects in the near future in population redistribution. the spatial mobility may be regulated through encouraging local-level human resource development and regional development efforts underway in the kingdom such as the creation of industrial, educational and medical townships at various geographic destinations. the kingdom is no way an exception in terms of sex differentials in migration flows. as seen elsewhere, males migrate more than females here also, as observed in the absolute numbers of in-migrants and out-migrants as well as net migrants. there are , males migrated from one area to another, as of . the corresponding figure for females was , . while male migrations are determined largely by employment opportunities, the female mobility is caused generally by marriages and family settlements. area wise, the number of migrants (in-migrants and out-migrants) varies in such a way that al-riyadh, makkah al-mokarramah, al-qaseem, eastern region, aseer, tabouk, jazan and najran have more male inmigrants and out-migrants than females; al-madinah al-monawarah, hail, northern borders, al-baha and al-jouf have less male in-migrants. however, male out-migrants dominate heavily in all areas. the migration rates range from . (jazan in-migrants) to . (al-riyadh in-migrants), giving rise to positive net migration rates for al-riyadh, makkah al-mokarramah, eastern region and tabouk. all the other areas experienced negative net migration rates. in other words, former four areas have more in-migrants than out-migrants; and the latter have more out-migrants than in-migrants. thus, the areas of saudi arabia experience high levels of spatial mobility, with the level of net migration varying largely from − . (al-baha) to . (al-riyadh). a recent demographic survey enlightens this issue by statistics on population classified by previous residence. it reveals a drastic change in the internal migration trend, comparatively. there is a rapid decline in the number of net migrants to a narrow level, of both males and females. all areas, except najran and al-jouf, show a similar trend ( fig. . ). immigrants constitute a considerable share of total population in the kingdom. (salam et al. ) . immigrants seeking jobs prompted by the development of oil fields foster not only the national economy but also immigrants' home countries (roudi-fahmi and kent ) . however, the crowding and mass gathering, resulting from an influx of job seekers, pose public health challenges such as accidents, corona virus infections, viral transmissions and middle east respiratroy syndrome -(mers), (memis and al-rabeeah ) demanding national attention. as seen in fig. . , the positive net migration plays a key role in the kingdom's population growth. this situation may be compared with other gcc states as the contributions of net migration remain more or less equal in all these nations. such a high role of migration on population growth may necessitate a review and reformulation of population and labour-related policies and programmes so that immigrants do not pose any burden on the gcc states, especially saudi arabia, in the near future. the unregulated import of labour played a more decisive role than natural increase in the higher population growth registered during the period - ( , , ) compared with - ( , , ) (forstenlechner and rutledge ; sufian ) . however, as compared with the other gcc countries-bahrain, qatar and united arab emirates (uae)-the effect of migration on population growth is found lesser in the kingdom, despite the push to develop infrastructure-power stations, government ministries and industries (khraif ) . perhaps, the saudization policies that changed labour and immigration laws since have influenced this trend. on the other hand, it is a fact that liberalization and globalization attract professional or skilled labour force from east asia and africa to western countries. with the changing labour visa regulations, a decline in immigration in the kingdom is expected in the future, which will create a population structure and distribution conducive for enabling an equitable treatment, policies and programmes. to achieve a positive relation between population dynamics and socioeconomic development, planning for migration at all levels should be associated with decentralization of decision-making in large urban centres and distribution of economic investment over a wide area, where urban population spreads out in medium and small centres (makki ). according to the us census data, net migrants in the kingdom kept on decreasing annually since , reaching the lowest level in . thereafter, with slight changes, their numbers declined and reached a negative level by , and the same trend continues at present. that is, the immigrants have started returning to their native countries more often (fig. . ). in contrast, the national censuses show a continuously increasing immigrant population in the kingdom but with lower growth rates, during - , as compared to - . in short, the migration data (net migrants) as given by the us census bureau do not tally with the national datasets. a similar trend is visibly noted in all the other gcc states but at different periods. oman started experiencing negative net migration since . similarly, qatar has the highest rate of net migration, followed by bahrain. definitely, these countries will soon follow the trends of saudi arabia, as the labour laws of saudi arabia are usually adopted by the other gcc states. these data also require comparisons with the national censuses for understanding the trend of immigration. saudi arabia has gcc's major population share as well as land share and the largest share of immigrants, during and . (aldossary et al. ) . also, in the professions having no language requirements, non-arabs are employed. higher emigration to other arab countries prevailed in the kingdom during and , which has changed to outside the arab world in , hopefully revealing the higher return migration from the arab countries as well as increased emigration of saudis to europe and america. this has resulted in the kingdom turning into "heterogeneous, multinational, and multi-religious with higher overall sex ratio, especially at prime working ages, creating social, economic, and security-related problems" (center for population studies ; forstenlechner and rutledge ; khraif a, b; fouad and al-badr ; ali ). the immigrant population (non-saudi) in the kingdom has a unique profile in terms of sex ratio, age distribution, residential status and geographic preferences, different from that of the native saudi population. migrants bring different demands and desires (forstenlechner and rutledge ) , showing a unique profile-adult to middle-aged single males with low educational levels, further impacting upon the national socio-demographics (alrouh et al. ) . sex ratio, the basic demographic indicator, varies from ( ) to ( ), with native sex ratio slightly more than ( in , in , in , in and ) but higher than in case of immigrants ( in , in , in , in and in ) . native sex ratios are close to in the childhood ages but favour males in the middle ages (above years), whereas that of immigrants favour males in the working ages and old ages in (table . ), but show marked differences in and . differences of immigrants from natives in terms of broad age groups are clear from fig. . , with a large majority of them being adult and middle-aged ( - years). among the natives, as of , in all, . per cent of population is aged - years, whereas among immigrants, the corresponding figure is . per cent, which is attributed to the immigration policies in the kingdom. there are marked changes observed thereafter in and . foreign-born population in the kingdom is employed on job contract, with the majority of them without a family status. thus, only the working-age people immigrate for employment, a --- , , , and leaving their family in their native countries. immigrants have rights over the occupation, not on their residential status. thus, the labour sector in the kingdom is dominated by males, except in schools and hospitals, thus reducing the opportunities of females in the job market. the sex differentials reflect the job market requirements. of late, the labour scenario of the kingdom of saudi arabia is undergoing changes in terms of labour laws, migration policies and sponsorshipbased employment contracts (forstenlechner and rutledge ) . effective implementation of such reforms is expected to develop a labour market steered by the native workforce. the labour market shall undergo a number of reforms in the near future before it stabilizes to a particular overall involvement of native labour force. as of , immigrants form . per cent of the total population in the kingdom; their proportions are higher in makkah al-mokarramah ( . per cent) and al-riyadh ( . per cent), eastern region and al-madinah al-monawarah (table . ). the number of persons per household, an indicator of population density at household level, shows differences between the natives and immigrants. while native households have more than six persons on an average, immigrants have just four, which could explain the immigrants' status (as forced bachelorship), expanded male adults and age-sex distribution. native households reflect an ideal family setup (father, mother and children), whereas a lesser proportion of immigrants live with their families. most immigrants live as single in bachelor quarters, employee compounds or in the so-called bedspace arrangements. thus, census counting of the immigrant population itself is an arduous task. housing, yet another indicator of social status, brings out certain unique differences of immigrants' living arrangements from that of natives. housing sector is composed of traditional housing, villas, apartments and others: natives live mostly in the first three types, whereas immigrants stay in apartments ( . per cent), traditional houses ( . per cent), and other types (table . ). apartments are available in the newly developed urban centres and upcoming townships, whereas the less urbanized areas have more traditional houses. concrete houses are commonly seen all over the kingdom but vary across areas, depending upon the climatic conditions and livelihoods. areas such as northern borders, eastern region, al-riyadh and al-jouf have more than per cent of their houses concreted, whereas the percentages are lower in jazan. more than per cent of saudi households in northern borders, al-riyadh, al-jouf and eastern house ownership is generally restricted to the natives, as per the kingdom's housing policies; however, there are few immigrants who own their housing as per special sanctions granted by the kingdom. but the rental housing system is more focussed on the immigrants; still, there are natives who also live in rented housings, which may be due to migrations or for the flexibility of labour force. one-third of the immigrants reside in rented houses, while the rest reside in official houses. rental houses remain less than per cent in al-qaseem and al-baha, implying that official houses are higher in proportions. but the proportions of natives living in rental houses are very low in these areas, as compared to immigrants. with the change in the type of housing, the housing infrastructuresources of power, water and sewage-changes, especially along areas. for example, the dependence of power varies from . per cent (hail) to . per cent (eastern region). native-immigrant variations in the utilization of public source of power are minimal- . per cent of natives as against . per cent of immigrants. among the areas, jazan has lesser proportion of native households, depending on public sources ( . per cent) and northern borders has least proportion of immigrant households ( . per cent). at the same time, eastern region has the highest proportion of native public sector power beneficiaries ( . per cent), whereas najran has the highest per cent of immigrant public sector power beneficiaries ( . per cent). but these cannot be considered as a constraint to quality of life as households have alternative sources such as private stations and private generators. in al-riyadh, makkah al-mokarramah and al-madina al-monawarah, public water supply users are less than per cent. it is in the eastern region that there are more than . per cent of households having access to public sector water supply. while the public sector water usage is lower among the natives ( . per cent), its usage is higher among immigrants ( . per cent). this is because of varying dependence on catchment tank water and well water. conversely, water remains as a severe constraint in the desert areas of the kingdom due to non-availability or difficulties of supplying to distant places. hence, some areas have less than per cent of households, depending upon the availability of public water sources (al-baha, najran and aseer). similar situation with the sewage system exists as well; the dependence on public sewage is less than half in the kingdom, ranging from . per cent (al-baha) to . per cent (eastern region). while the major areas have higher proportions, other areas have lesser proportions of households depending upon public sewage. a large proportion of immigrant households depends upon public sewage ( . per cent) as against the natives ( . per cent), indicating the type of housing along areas. native households have different accesses like ditches and private sewages. as pointed out earlier, immigrants are located more in the urban areas as per the preliminary reports of census, that is, . per cent of immigrant population as against . per cent of native population live in urban areas (table . ). immigrant females are concentrated more in the urban areas ( . per cent) as against immigrant males ( . per cent), which reflects the job demands. in comparison, the native females are lesser in urban areas. there are regional differences in this dimension as well. the kingdom of saudi arabia is vibrant with high levels of internal migration flows across the administrative areas. there exits tremendous and varying degrees of pull and push factors determined by socioeconomic development, industrialization and urbanization. the major in-migrating areas are tabouk, al-riyadh and eastern region, while the major outmigrating destinations are al-baha, jazan, hail, al-qaseem, aseer and northern borders. a few areas remain more or less stable without pulling or pushing native population. public sector employment and proximity to metropolis (riyadh, jeddah/makkah or dammam) are major pull factors. makkah al-mokarramah maintains the status without being influenced significantly by the migration flows. again, as seen elsewhere, males migrate more than females, as observed in the absolute numbers of inmigrants and out-migrants as well as net migrants. the regional development-infrastructure development and promoting medium-sized cities-with an aim to create employment encourages native population to continue living at their own birth places. those areas experiencing substantial levels of immigration require redistribution policies, both for population and infrastructure development programmes. the spatial mobility may be regulated by encouraging local-level human resource development and regional development efforts underway in the kingdom such as the creation of industrial, educational and medical townships at various geographic destinations. saudi arabia is the largest country in the gcc in terms of both land area and population, thus having the highest level of international migration within the arab world and beyond. the changing labour laws and saudization efforts shall curb this situation, bringing a balance between the demand and supply in the labour market. the hiked net migration rate ( ) ( ) ( ) ( ) ( ) ( ) has immediately been brought to unity, which will reduce at prevailing emigration trend. expatriates, in a way, complicate the demographics of saudi arabiasex ratio, age-sex distribution, dependency ratio, regional distribution of population, urban share and housing conditions. demographic transition underway in the country is reflected in the native age-sex distribution. the positive net migration plays a key role in the kingdom's population growth. such a high role of migration on population growth may necessitate a review and reformulation of population and labour policies and programmes so that immigrants would not pose any burden in the gcc states, especially saudi arabia, in the near future. out of the total immigrants in the kingdom, three-fifths are non-arabs. of late, the labour scenario of the kingdom of saudi arabia is undergoing changes in terms of labour laws and migration policies. effective implementation of such reforms is expected to develop a labour market steered by the native workforce. the labour market shall undergo a number of reforms in the near future before it stabilizes to a particular overall desired optimum level of expatriate labour force. health care and nursing in saudi arabia labour immigration in the arab gulf states: patterns, trends and problems population spatial distribution policies in saudi arabia demographic and health indicators in gulf cooperation council nations with an emphasis on qatar organization of the saudi health system dynamics of saudi arabian population: analysis through four censuses - , population dynamics of large middle eastern cities declining fertility in the arab peninsula the gcc's "demographic imbalance": perceptions, realities and policy options the composition of population with respect to sex in saudi arabia migration and home ownership permanent versus temporary rural migrants in riyadh, saudi arabia -a logit analysis of their intentions of future mobility residential mobility in the city of riyadh: a study of its directions, reasons and characteristics the labor force in saudi arabia: spatial dimensions and socioeconomic and demographic characteristics fertility in saudi arabia: levels and determinants. xxiv general population conference urbanization and growth of cities in saudi arabia demographic imbalances in gcc: solutions and confrontations fertility behaviours of grazing groups in suman and northern parts of saudi arabia uneven development: comparing the indigenous health care workforce in saudi arabia, bahrain and oman regional and urban population size weights in saudi arabia public health management of mass gatherings: the saudi arabian experience with mers-cov challenges and opportunities -the population of the middle east and north africa components and public health impact of population growth in the arab world the demography of saudi arabia the demography of the arab world and the middle east from the s to the kingdom of saudi arabia-human development report country program document for saudi arabia the use of urban observatories as a tool for localizing urban and social policy. economic and social council for western asia the demographic dilemma of the arab world: the employment aspect key: cord- -xogzl lv authors: alsuheel, ali mohammed; ali, abdelwahid saeed; al-hakami, ahmed musa; shati, ayed abdullah; chandramoorthy, harish c.; al-qahtani, saleh mohammed title: human metapneumovirus in pediatric patients with acute respiratory tract infections in the aseer region of saudi arabia date: - - journal: saudi j med med sci doi: . /sjmms.sjmms_ _ sha: doc_id: cord_uid: xogzl lv background: human metapneumovirus (hmpv) is a paramyxovirus known to cause acute respiratory tract infections in children and young adults. to date, there is no study from the aseer region of saudi arabia determining the proportion and severity of hmpv infection among pediatric hospitalized patients with respiratory infections. objectives: the objective of this study is to determine the presence of hmpv antigens in the nasopharyngeal secretions of pediatric patients hospitalized with respiratory tract infections in the aseer region of saudi arabia. materials and methods: this prospective, serological hospital-based study included all pediatric patients who were admitted to aseer central hospital, abha, saudi arabia, from july to november with upper and/or lower respiratory tract infections. basic demographics of patients and their clinical data on and after admission were recorded. direct fluorescent antibody assay was used to detect the presence of hmpv antigens in the obtained nasopharyngeal secretion specimens. results: during the study, pediatric patients were hospitalized due to upper and/or lower respiratory tract infections, of which . % were positive for hmpv. these patients were aged months to years, were from abha city or its surrounding localities and were mostly ( . %) hospitalized during autumn or winter. the most common diagnosis on admission was bronchopneumonia ( . %) and aspiration pneumonia ( . %), and some patients also had underlying chronic conditions such as chronic heart disease ( . %) and bronchial asthma ( . %). conclusions: the results obtained indicated that hmpv is a potential etiologic factor for the commonly occurring acute respiratory infections in hospitalized children from the aseer region of saudi arabia. hmpv infection was also found to be associated with complicated respiratory conditions such as bronchopneumonia, chronic heart disease and bronchial asthma. human metapneumovirus (hmpv) is a single-stranded rna-enveloped virus, recently classified in the order mononegavirales, family pneumoviridae, genus metapneumovirus and species hmpv. it was first isolated in the netherlands by van den hoogen et al., [ , ] and is now a known causative agent of upper and lower respiratory tract infections in children and adults. hmpv infections have been reported in australia, [ ] canada, [ ] the united states, [ ] the united kingdom, [ ] hong kong, [ ] south africa, [ ] mexico, [ ] spain [ ] and peru. [ ] however, in the middle east, there have only been few reports of hmpv infections, mainly as sporadic infections in egypt, [ ] jordan, [ ] kuwait [ ] and saudi arabia. [ ] along with respiratory syncytial virus (rsv) infections, hmpv is now recognized as a primary etiologic agent for acute upper and lower respiratory tract infections in pediatrics. [ , ] in a study from mexico, it was found that the number of hmpv infections increased in children aged - months as compared with those in younger age groups, whereas rsv infections were inversely proportional to increase in age. [ ] co-infection with both viruses can also occur, resulting in a more complicated and serious clinical disease. [ , ] in addition to the pediatric population, studies have also found hmpv to infect adults [ ] and elderly people. [ ] in terms of transmission, hmpv spreads through contact with contaminated secretions, i.e., droplet, aerosol or fomites. hospital-acquired hmpv infections have also been reported. [ ] in young children, infections are usually not asymptomatic, and bronchiolitis, with or without pneumonia, is the most common associated presentation. [ , , ] other reported conditions include bronchial asthma exacerbation, otitis media, pneumonitis, flu-like illness and community-acquired pneumonia. [ ] in adults, hmpv has been associated with bronchitis, pneumonia and exacerbations of both bronchial asthma and chronic obstructive pulmonary disease. [ , ] in terms of detection, reverse transcriptase-polymerase chain reaction (rt-pcr) is a sensitive and commonly used method to detect hmpv. [ ] real-time rt-pcr is also commonly used for detecting hmpv in clinical specimens with many genomic target sequences. [ , ] a touch-down genomic amplification protocol for the diagnosis of acute viral respiratory tract infections has also been used previously. [ ] the enzyme-linked immunosorbent assay for hmpv diagnosis is a simple and specific serological test for anti-hmpv antibodies detection. [ ] immunofluorescence using specific antibodies is routinely used for detecting hmpv antigens, particularly in epidemiological studies. [ ] however, cell culturing techniques have a low sensitivity in detecting hmpv from respiratory tract secretions, as the virus exhibits extremely limited types of cell tropism. [ , , , ] in saudi arabia, there is a paucity of data regarding the occurrence of hmpv and its role in complicated clinical cases of commonly reported respiratory infections. therefore, the current study aimed to determine the role of hmpv in the respiratory tract infections' severity and complications among hospitalized children in the aseer region, where no such study has previously been conducted. the study was conducted after obtaining approval from the ethical committee of college of medicine, king khalid university, saudi arabia (kku research ethics committee meeting no. rec # - - ; dated january , ) this prospective, serological study included pediatric patients who were admitted to aseer central hospital, abha, kingdom of saudi arabia, from july to november with upper and/or lower respiratory tract infections. aseer central hospital is the largest tertiary care referral hospital in the aseer region, and thus its sample is representative of the area. data such as age, gender, clinical presentation and current medications were collected using an objectively prepared questionnaire. informed consent was obtained from the parents/guardians of all patients before sample collection. nasopharyngeal secretions were collected from all hospitalized patients included in this study using the standard collection method. briefly, physicians collected the nasopharyngeal secretions with the help of a sterile feeding tube connected to a vacuum pump. following the vacuum application, the tip of the tube was cut and placed into a sterile container labelled with the patient's name and identification number. the container was then transported to the virology laboratory at the department of microbiology and clinical parasitology, college of medicine, king khalid university, abha, saudi arabia, and either processed on the same day or stored at − °c. specimens were processed according to the manufacturer's instructions for the direct fluorescent antibody (dfa) kit (oxoid ltd., cambridge, uk) with minor modifications. samples were transferred to an eppendorf tube containing ml of phosphate-buffered saline (pbs; ph . ). the specimens were gently vortexed for s to reduce the viscosity and dilute the mucus. samples were then centrifuged at rpm for min to separate the cells from the mucus. the supernatant was removed, and the cells in the pellets were used for dfa staining. the authors chose to use dfa because it has been found to be a useful technique for wider hmpv epidemiological studies. [ ] preparation of cells the cell suspension was washed several times with pbs and the final cell deposit was resuspended in ml pbs (ph . ). the cells were then gently agitated by pipetting up and down until the cellular material was released from the mucus. additional pbs was added until a smooth suspension was obtained, and any visible flecks of mucus were removed. after the cell separation process was completed, the obtained cell suspension was centrifuged at room temperature ( °c- °c) for min at rpm and the supernatant was discarded. the final cell deposit was resuspended in pbs to dilute any remaining mucus and maintain high cell density. a volume of µl of the resuspended cell deposit was placed in slides with -mm-diameter wells. the specimens were then allowed to air dry thoroughly and fixed with fresh acetone at room temperature ( °c- °c) for min. the slide was air-dried after fixation. a volume of µl of imagen™ hmpv reagent (oxoid ltd., cambridge, uk), which contains monoclonal antibodies against hmpv conjugated to fluorescein isothiocyanate, was added to the fixed cell preparation on the slide to cover the wells. the same amount was also added to the positive control slide. the slides were then incubated with the reagent in a moist chamber for min at °c. following incubation, excess reagent was washed off with pbs, and the slide was gently washed in an agitating bath containing pbs for min. the pbs was drained off, and slide was allowed to air dry at room temperature ( °c- °c). one drop of imagen™ hmpv mounting fluid was added to the center of each well, and cover-slip was placed over the mounting fluid and specimen to ensure that there are no trapped air bubbles. the stained slides were immediately examined under epifluorescence microscope at × and then × . apple-green fluorescence was observed in the cells infected with hmpv, whereas non-infected cells appeared as red color because they were stained with the evans blue counterstain. images of these cells were captured using a microscopic camera (nikon-ds-fi , nikon corp., tokyo, japan) and archived. during the study, a total of pediatric patients were hospitalized based on upper and/or lower respiratory tract infections. of these ( . %) patients tested positive for hmpv antigens, as demonstrated by dfa from the nasopharyngeal secretions [ figure ]. table provides the demographic and clinical presentation data of all hmpv-positive patients. the age of these patients ranged from months to years and all were saudi nationals except one infant, who was a jordanian by nationality but was born and raised in saudi arabia. from the patient's demographics, it was observed that hmpv antigens were detected not only in patients from abha but also among those from its bordering areas, namely, algahama, bilahmar, ahud rufida, sarat abeedah, khamis mushait and bilasmer. three of the nine positive cases were found from abha ( . %), and one positive case from each of the previously mentioned six cities was reported ( . %). of the nine hmpv-positive patients, seven ( . %) were hospitalized during the autumn and winter of - . in the hmpv-positive patients, the symptoms included fever ( . %), cough ( . ), shortness of breath ( . %), nasal congestion ( . %), cyanosis ( . %) and stridor ( . %). these patients also had underlying chronic illnesses such as chronic heart disease ( . %) and bronchial asthma ( . %), and most had tachypnea ( . %). on physical examinations, bilateral crepitation and wheezing were found to be the major findings along with bronchopneumonia ( . %) and aspiration pneumonia ( . %). in saudi arabia, although few studies have reported the incidence, epidemiological elements and genetic diversity of hmpv in some regions, [ , , ] there are no reports on the association between hmpv infections and the clinical presentations of respiratory tract infections among pediatrics. the current study found that in the aseer region of saudi arabia, about % of hospitalization among pediatrics with respiratory tract infections between july and november was due to hmpv infections. in addition, this study also found that hmpv infections were associated with presentation of acute respiratory symptoms, thereby highlighting the role of the infection in complicating the course of the disease. the results of the present study concur with several other studies demonstrating an association between hmpv infection and acute respiratory conditions such as bronchopneumonia and pneumonia. [ , ] a previous study implicated hmpv as a causative agent for severe and acute respiratory infections among pediatric patients, [ ] which is similar to the findings of the current study. another study found that children with hmpv infection are likely to have immunodeficiency; however, the current study was not able to substantiate these findings as none of the patients were found to be immunocompromised. [ ] the prevalence of hmpv infection of the current study (about %) was similar to that reported in studies from saudi arabia and kuwait. [ , ] however, other similar studies that used direct immunofluorescence assays for the detection of hmpv antibodies in sera of patients revealed much higher prevalence rates. [ ] this suggests that different results can be obtained with different diagnostic techniques for hmpv infection. in the current study, we used dfa with monoclonal antibody, which has previously been shown to have % specificity, thereby indicating the reliability of our results. [ ] the current study did not find any gender predilection in terms of the infections; these findings are in accordance with that of bastien et al. [ ] and kahn. [ ] in this study, all nine hmpv-positive children were from abha or its surrounding areas. these areas are known for their high altitude, low temperature and low oxygen tension. it was well known that the prevalence of viral respiratory infections is high in cold and dry areas. [ ] in addition, almost % of the hmpv-positive cases were in children who had been admitted during the autumn and winter seasons. it is also known that the majority of the viruses responsible for bronchiolitis and bronchopneumonia have their peak infectivity during winter and late autumn, with only sporadic cases through other seasons. [ , ] the hmpv-positive patients in the current study had fever, cough, nasal congestion, cyanosis, stridor and shortness of breath, while some also had underlying chronic illnesses such as chronic heart disease and bronchial asthma; similar hmpv-associated illnesses were observed in another study. [ ] physical examination revealed wheezing and bilateral crepitation and clinically, the most common presentations were bronchopneumonia and aspiration pneumonia. these findings are in line with those of williams et al., [ ] who found significant association between hmpv and wheezing exacerbations and/or bronchiolitis in infants and young children. in the aseer region of saudi arabia, hmpv was found to be responsible for about one-tenth of hospitalizations in children with acute respiratory tract infections. this study also confirmed that hmpv infection is associated with presentation of acute respiratory symptoms. ictv virus taxonomy profile: pneumoviridae a newly discovered human pneumovirus isolated from young children with respiratory tract disease evidence of human metapneumovirus in australian children human metapneumovirus infection in the canadian population human metapneumovirus infection in the united states: clinical manifestations associated with a newly emerging respiratory infection in children human metapneumovirus in severe respiratory syncytial virus bronchiolitis children with respiratory disease associated with metapneumovirus in hong kong human metapneumovirus infection in hospital referred south african children human metapneumovirus infections in mexico: epidemiological and clinical characteristics human metapneumovirus infections in hospitalised infants in spain human metapneumovirus study of human metapneumovirus-associated lower respiratory tract infections in egyptian adults human metapneumovirus in hospitalized children in amman human matapneumovirus in patients with respiratory tract infection in kuwait human matapneumovirus and human coronavirus infection and pathogenicity in saudi arabia children hospitalized with acute respiratory illness viral respiratory infections in the neonatal intensive care unit-a review comparison of clinical characteristics of human metapneumovirus and respiratory syncytial virus infection in hospitalized young children a case series on common cold to severe bronchiolitis and pneumonia in children following human metapneumovirus infection in sri lanka human metapneumovirus in adults. viruses : ; - . . van den hoogen bg. respiratory tract infection due to human metapneumovirus among elderly patients human metapneumovirus and lower respiratory tract disease in otherwise healthy infants and children the role of human metapneumovirus in the critically ill adult patient clinical and radiologic characteristics of human metapneumovirus infections in adults detection and genetic diversity of human metapneumovirus in hospitalized children with acute respiratory infections in india real-time pcr probe optimization using design of experiments approach a touchdown nucleic acid amplification protocol as an alternative to culture backup for immunofluorescence in the routine diagnosis of acute viral respiratory tract infections diagnosis of human metapneumovirus and rhinovirus in patients with respiratory tract infections by an internally controlled multiplex real-time rna pcr diagnosis of human metapneumovirus by immunofluorescence staining with monoclonal antibodies in the north-east of england epidemiology of human metapneumovirus human metapneumovirus: review of an important respiratory pathogen evaluation of a commercial direct fluorescent-antibody assay for human metapneumovirus in respiratory specimens viral etiology of respiratory infections in children in southwestern saudi arabia using multiplex reverse-transcriptase polymerase chain reaction molecular epidemiology of human metapneumovirus in riyadh province, saudi arabia clinical impact and diagnosis of human metapneumovirus infection detection of human metapneumovirus by direct antigen test and shell vial cultures using immunofluorescent antibody staining seasonality of viral respiratory infections in southeast of brazil: the influence of temperature and air humidity seasonal occurrence of human metapneumovirus infections in croatia genetic diversity, seasonality and transmission network of human metapneumovirus: identification of a unique sub-lineage of the fusion and attachment genes human metapneumovirus infection plays an etiologic role in acute asthma exacerbations requiring hospitalization in adults human metapneumovirus infection in children hospitalized for wheezing there are no conflicts of interest. key: cord- -gljfslhs authors: al-hanawi, mohammed k.; angawi, khadijah; alshareef, noor; qattan, ameerah m. n.; helmy, hoda z.; abudawood, yasmin; alqurashi, mohammed; kattan, waleed m.; kadasah, nasser akeil; chirwa, gowokani chijere; alsharqi, omar title: knowledge, attitude and practice toward covid- among the public in the kingdom of saudi arabia: a cross-sectional study date: - - journal: front public health doi: . /fpubh. . sha: doc_id: cord_uid: gljfslhs background: saudi arabia has taken unprecedented and stringent preventive and precautionary measures against covid- to control its spread, safeguard citizens and ensure their well-being. public adherence to preventive measures is influenced by their knowledge and attitude toward covid- . this study investigated the knowledge, attitudes, and practices of the saudi public, toward covid- , during the pandemic. methods: this is a cross-sectional study, using data collected via an online self-reported questionnaire, from , participants. to assess the differences in mean scores, and identify factors associated with knowledge, attitudes, and practices toward covid- , the data were run through univariate and multivariable regression analyses, respectively. results: the majority of the study participants were knowledgeable about covid- . the mean covid- knowledge score was . (sd = . , range: – ), indicating a high level of knowledge. the mean score for attitude was . (sd = . , range: – ), indicating optimistic attitudes. the mean score for practices was . (sd = . , range: – ), indicating good practices. however, the results showed that men have less knowledge, less optimistic attitudes, and less good practice toward covid- , than women. we also found that older adults are likely to have better knowledge and practices, than younger people. conclusions: our finding suggests that targeted health education interventions should be directed to this particular vulnerable population, who may be at increased risk of contracting covid- . for example, covid- knowledge may increase significantly if health education programs are specifically targeted at men. coronavirus disease is defined as an illness caused by a novel coronavirus, now called severe acute respiratory syndrome coronavirus (sars-cov- ; formerly called -ncov). covid- is an emerging respiratory infection that was first discovered in december , in wuhan city, hubei province, china ( ) . sars-cov- belongs to the larger family of ribonucleic acid (rna) viruses, leading to infections, from the common cold, to more serious diseases, such as middle east respiratory syndrome (mers-cov) and severe acute respiratory syndrome (sars-cov) ( ) . the main symptoms of covid- have been identified as fever, dry cough, fatigue, myalgia, shortness of breath, and dyspnoea ( , ) . covid- is characterized by rapid transmission, and can occur by close contact with an infected person ( ) ( ) ( ) ( ) ( ) . the details on the disease are evolving. as such, this may not be the only way the transmission is occurring. covid- has spread widely and rapidly, from wuhan city, to other parts of the world, threatening the lives of many people ( ) . by the end of january , the world health organization (who) announced a public health emergency of international concern and called for the collaborative effort of all countries, to prevent its rapid spread. later, the who declared covid- a "global pandemic" ( ) . following the who declaration, countries around the globe, including the kingdom of saudi arabia (ksa), have been leaning on response plans to respond to the pandemic and contain the virus. following the confirmation of its first case of covid- , on monday march , the saudi government has been vigilantly monitoring the situation and developing countryspecific measures that are in line with the who guidelines in dealing with the outbreak ( ) . these includes suspending all inbounds and outbounds flights, closing all malls and shops in the country, except pharmacies and grocery stores, and closing down schools and universities. umrah visas have been suspended, as have prayers at mosques, including the two holy mosques in mekkah and almadina. on march , the government imposed a nationwide curfew to restrict people movements for most of the day hours. despite the unprecedented national measures in combating the outbreak, the success or failure of these efforts is largely dependent on public behavior. specifically, public adherence to preventive measures established by the government is of prime importance to prevent the spread of the disease. adherence is likely to be influenced by the public's knowledge and attitudes toward covid- . evidence shows that public knowledge is important in tackling pandemics ( , ) . by assessing public awareness and knowledge about the coronavirus, deeper insights into existing public perception and practices can be gained, thereby helping to identify attributes that influence the public in adopting healthy practices and responsive behavior ( ) . assessing public knowledge is also important in identifying gaps and strengthening ongoing prevention efforts. thus, this study aims to investigate the knowledge, attitudes and practices (kap) of ksa residents, toward covid- during the pandemic spike. to the researchers' knowledge, this is the first study to investigate covid- kap, and associated sociodemographic characteristics among the general population of the ksa. the findings of this study are expected to provide useful information to policymakers, about kap among the saudi population, at this critical time. the findings may also inform public health officials on further public health interventions, awareness, and policy improvements pertaining to the covid- outbreak. this cross-sectional study was conducted among the general population of saudi arabia, from march , to march . given the social distancing (physical distancing) measures and restricted movement and lockdowns, data were collected online, via a self-reported questionnaire, using surveymonkey. given the high internet usage among people in the ksa, a link to the survey was distributed to respondents, via twitter and whatsapp groups. the link was also posted on the king abdulaziz university website. the larger the target sample size, the higher the external validity and the greater the generalizability of the study ( ) . this study aimed to maximize reach and gather data from as many respondents as possible. according to the latest ksa census, saudi arabia has a population of , , ( ) . the representative target sample size needed, to achieve the study objectives and sufficient statistical power, was calculated with a sample size calculator ( ) . the sample size calculator arrived at , participants, using a margin of error of ± %, a confidence level of %, a % response distribution, and , , people. the self-reported questionnaire was developed by the authors, according to guidelines for the community of covid- , by the centers for disease control and prevention (cdc) ( ) . the questionnaire was conducted in arabic language. it was initially drafted in english by h.z.h., and y.a., and was translated from english to arabic by m.k.a and m.a. the questionnaire was translated then back to english by n.a and w.k to ensure the meaning of the content. on the first page of the online questionnaire, respondents were clearly informed about the background and objectives of the study. respondents were informed that they were free to withdraw at any time, without giving a reason, and that all information and opinions provided would be anonymous and confidential. respondents living in saudi arabia, aged years or older, understand the content of the questionnaire, and agree to participate in the study were instructed to complete the questionnaire. online informed consent were obtained before proceeding with the questionnaire. the questionnaire consisted of four primary sections. the first section gathered information on respondents' sociodemographic characteristics, including age, gender, marital status, education level, work status, region of residence, and income level. the second section assessed participants' knowledge of covid- . this section included items on modes of transmission, clinical symptoms, treatment, risk groups, isolation, prevention and control. the third section assessed participants' attitudes toward covid- , using a five-point likert scale. for each of six statements, respondents were asked to state their level of agreement, from "strongly disagree, " "disagree, " "undecided, " "agree, " or "strongly agree." the final section of the questionnaire assessed the respondents' practices. this section consisted of five questions related to practices and behavior, including (a) going to social events with large numbers of people, (b) going to crowded places, (c) avoiding cultural behaviors, such as shaking hands (d) practicing social distancing, (e) washing hands after sneezing, coughing, nose-blowing, and, recently, being in a public place. for sociodemographic variables, gender was coded as one for men, and zero for women. the age variable was divided into categories: - (reference category), - , - , - , and ≥ . marital status was captured as binary, and a value of one was used for marriage and zero for otherwise. education was categorized into high school or below (reference category), college/university degree, and postgraduate degree. work status was broken down into government employee (reference category), non-government employee, retiree, selfemployed, and unemployed. monthly income (saudi riyal, sr = usd . ) was divided into eight categories: <sr , (reference category); sr , to < , , sr , to < , , sr , to < , , sr , to < , , sr , to < , , sr , to < , , and sr , or more. we also controlled for the administrative regions: almadina almonawra, albaha, aljouf/quriat, aseer/bisha, eastern region, haiel, jazan, najran, northern borders, qaseem, riyadh, tabouk, and the western region. respondents were asked to respond to knowledge items as either true or false, with an additional "don't know" option. incorrect or uncertain (don't know) responses were given a score of zero, and correct answers were assigned a score of one. the total score for knowledge ranged from zero to , with high scores indicating better knowledge of covid- . items were evaluated for internal reliability, using cronbach's α. cronbach's alpha coefficient was . , indicating internal reliability ( ) . in the section on attitudes, scores were calculated based on the respondents' answers to each attitudinal statement, = strongly disagree, = disagree, = undecided, = agree, and = strongly agree. scores were calculated by averaging respondents' answers to the six statements. total scores ranged from six to , with high scores indicating positive attitudes. the likert scales were assessed for internal reliability, using cronbach's α. cronbach's alpha coefficient was . , indicating internal reliability. in the section on practices, respondents were asked to respond "yes" or "no" to the items. a score of one was given to answers that reflected good practice, and a score of zero was given for answers that reflected bad practice. the total score ranged from zero to five, with high scores indicating better practices. this study employed primarily univariate and multivariable regression data analyses. univariate analysis was used to tabulate the frequency of social and demographic statistics. one-way analysis of variance (anova) was used to assess differences in mean values for kap scores. because the scores were continuous, the overall mean differences were estimated using a bartlett test ( , ) . a multivariable linear regression analysis was performed, to identify factors related to knowledge, attitudes, and practice. all analyses were conducted using stata software (statacorp lp, texas, usa). all procedures performed in this study, involving human participants, complied with the institutional and/or national research committee ethical standards, and the helsinki declaration and subsequent amendments or equivalent ethical standards. the study was designed and conducted in accordance with the ethical principles established by king abdulaziz university. therefore, ethical approval was obtained from the biomedical ethics research committee, faculty of medicine, king abdulaziz university . a total of , participants completed the questionnaire. after excluding respondents who reported living outside the ksa, the final sample consisted of , participants. table shows the social and demographic characteristics of the study participants. as shown in table , the mean covid- knowledge score was . (sd = . , range: - ), and the overall accuracy rate for the knowledge test was . % ( . / * ). the mean attitude score for covid- was . (sd = . , range: - ), indicating positive attitudes. the mean score for practices for covid- was . (sd = . , range: - ), indicating good practices. of the total sample, ( . %) were women, and ( . %) were men. the majority of the sample ( . %) were between the ages of and . of the participants, , were married ( . %) and , were unmarried ( . %). more than half of the sample ( . %) had a college or university degree. respondents were grouped according to monthly income, with ( . %) in the < sr group, and ( . %) in the ≥ sr , group. in terms of work status, , ( . %) were unemployed, and ( . %) were retired. tables - show the responses to items related to kap towards covid- . we also assessed the level of kap, across the various income groups. figures - show the results. figure shows that the covid- knowledge score increases with income. the lowest score was for respondents in the lowincome category, < sr , and the highest score was for respondents with an income of sr , to < , . for attitudes, figure shows that there were no discernible patterns across income groups. furthermore, with regard to practices, there was little variation between income groups, as shown in figure . looking at the univariate statistics for each variable of interest, we took another step to assess the difference in the scores for kap. table shows the results. as shown in table , all scores for kap, were statistically different at the % significance level, for all age and income groups. although, across genders, there was a statistically significant difference in attitudes and practices scores, there was no difference in knowledge scores. although assessments showed that knowledge scores were not statistically different between regions, attitudes and practices scores were significantly different at the % level. apart from the univariate and non-parametric analyses performed in previous sections, we also focused on regression analysis. scores were logged for all variables, and interpreted using ordinary least squares (ols). increased scores imply increased knowledge, practices, and attitudes. the results are shown in table . table shows that, for knowledge of covid- , age groups - , - , - and ≥ , are more knowledgeable about covid- than the reference group ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) . all variables for age groups - (β = . ; p < . ), - (β = . ; p < . ), - (β = . ; p < . ) and ≥ (β = . ; p < . ), are statistically significant at the % level. however, attitudes follow a different trend. only the age group - (β = − . ; p < . ) is significantly different from baseline. in practices for covid- , age groups - (β = . ; p < . ), - (β = . ; p < . ), and - (β = . ; p < . ), are associated with good practices. regarding gender, the results indicate that, compared to women, men have lower knowledge (β = − . ; p < . ), lower positive attitudes (β = − . ; p < . ), and few good practices for covid- (β = − . ; p < . ). no difference in kap toward covid- was observed by marital status. however, the relationships between income, region, education, and variables of interest, are heterogeneous, suggesting substantial differences. we also examined the association between kap scores. because all were logs, the interpretation would be akin to the elasticity. therefore, table shows that every increase of % in knowledge score is associated an increase in attitude and practices scores, of . and . , respectively. covid- is an emerging infectious disease that poses a significant threat to public health. given the serious threats imposed by covid- and the absence of a covid- vaccine, preventive measures play an essential role in reducing infection rates and controlling the spread of the disease. this indicates the necessity of public adherence to preventive and control measures, which is affected by their knowledge, attitudes, and practices ( , ) . in our study, the high rate of correct answers to knowledge-related questions among participants, was not surprising. this may be due to the characteristics of the sample, as % had a college or university degree, or above, and % were over years old. it may also be due to the distribution of the questionnaire, amid the covid- outbreak. in that time, people may have gained awareness and knowledge about the disease and its transmission, via television, news and media platforms, to protect themselves and their families. the positive association found between knowledge, and educational background and age, supports our claim. most of the participants in our study ( %) were aware of the clinical symptoms, and % knew that there is no clinically approved treatment for covid- as of the date of this manuscript. viral infections have been documented to be highly contagious among people in close proximity ( ) . however, approximately half of the respondents were unaware that sars-cov- could spread from person-to-person in close proximity. it was also evident that the current general population ( %) had little knowledge of when and whom wearing masks to prevent infection. according to the who and the cdc, faces mask should only be worn by those who are sick or caring for people suspected of having covid- ( , ) . these findings highlight the need to continue to encourage and emphasize maintaining social distancing, as a means of preventing the spread of the virus. it is important to note that there has been a great deal of efforts at all levels by the government, including public awareness campaigns. the saudi arabian ministry of health (moh) has conducted an intensive awareness campaign, communicated via its website, television and various social media. the moh has produced a guide to covid- , to provide residents with facts and precautionary messages in more than languages. the moh also works with the public and the media, especially via social media platforms. these early actions on engaging the public in prevention and control measures, as well as efforts to combat rumors and misinformation, have been greatly expanded ( ). it is worth noting that the ksa is in the unique position of having dealt successfully with two outbreaks of viral origin, of related viruses ( ) ( ) ( ) ( ) ( ) . this unique experience has helped the government in taking prompt response and precautionary measures against covid- to control its spread. significant predictors of participant knowledge in this study were age, gender, educational level, and income level. this finding is supported by other studies that have found that older, female, and more educated respondents are more knowledgeable about emerging communicable diseases ( , ) . we also found that high income earners are more knowledgeable about covid- . education, age, and income have been documented to be highly relevant to knowledge ( ) . our findings suggest that greater emphasis should be placed on mass media, to target low-income, low-educated, young people, and men to improve public knowledge on the covid pandemic, through awarenessraising interventions. concerning attitudes, participants showed a positive and optimistic attitude toward covid- . approximately % concur that the virus can be successfully controlled, and % are convinced that the saudi government will control the pandemic. positive attitudes and high confidence in the control of covid- can be explained by the government's unprecedented actions and prompt response in taking stringent control and precautionary measures against covid- , to safeguard citizens and ensure their well-being. these measures include the lockdown, and the suspension of all domestic and international flights, prayer at mosques, schools and universities, and the national curfew imposed on citizens. this finding is consistent with a recent study conducted in china, where the majority of participants were convinced that the disease is curable and that their country will combat the disease ( ) . however, these results contrast with other findings that suggest people tend to express negative emotions, such as anxiety and panic, during a pandemic that could affect their attitude ( ) . nevertheless, our results show that the participants' high knowledge of covid- translates into good and safe practices, during the covid- pandemic, which suggests that the practices of saudi residents are very cautious. almost % of respondents refrained from attending social events, % avoided crowded places, and % avoided shaking hands. respondents adopted good and safe practices, as a result of saudi arabia's health authorities providing education and outreach materials, to increase public understating of the disease, and influence behavioral change. finally, the study findings may be useful to inform policymakers and healthcare professionals, on further public health interventions, awareness-raising, policies, and health education programs. men were significantly less likely to have knowledge, optimistic attitudes, and appropriate or safe practices toward covid- . these findings are consistent with other studies showing that, in response to sars and mers, men were significantly less likely take preventive and protective measures than women ( , , ) . our finding suggests that targeted health education interventions should be directed to this particular vulnerable population at high risk of contracting covid- . for example, covid- knowledge may increase significantly, if health education programs are specifically targeted at men. health information can be sent to women (wives, sisters, mothers) who live with men, which may influence their practices, as suggested by a study in hong kong ( ) . to the researchers' knowledge, this is the first study to investigate kap toward covid- , in the general population of the ksa. data collection took place weeks after the ksa confirmed its first covid- case. therefore, the prompt results may help health authorities to plan preventive strategies for future events. however, in interpreting the results of this study, some limitations should be considered. data used in the analysis of this study were self-reported, which might suffer from reporting bias. future research might employ administrative data to address this issue. furthermore, there may be some endogenous variables: general attitude and expectation from the government, personal hygiene, for example. however, even if we were to undertake causality analysis, we could not be in a position to do proper econometric identification because the data we used could not have a valid instrument to eliminate the endogeneity. additionally, community-based national sampling surveys were not feasible during this particular period. as such, data were collected online, through self-reported questionnaires, depending on the authors' networks. therefore, the majority of the respondents were in the western region, where most of the authors come from. further research should cover the perceptions of all regions of the country. finally, this study did not address causation. therefore, the regression results should be interpreted as relevant, as some variables may be endogenous. that said, the implication is for the objective of future research to assess whether there is a relationship between covid- knowledge and mortality, household consumption patterns, and the demand for unprescribed flue medication. this is the first study to investigate kap for the covid- outbreak, among the general population of saudi arabia. our findings suggest that saudi residents, especially women, have good knowledge, positive attitudes, and good practices toward covid- . knowledge of the disease is considered the first stepping stone to any health education activity that is implemented. knowing the causes and transmission sources of a disease, increases the likelihood that people will become more aware of the spread of communicable diseases, and of the preventive measures to slow transmission. the results of this study suggest that more emphasis should be placed on less educated, lower income, and men. the findings may help policymakers identify the target populations, for covid- prevention and health education. the datasets generated and/or analyzed during the current study are not publicly available due to privacy and confidentiality agreements as well as other restrictions, but are available from the corresponding author (mohammed k. al-hanawi) on reasonable request. all authors made substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data, took part in drafting the article or revising it critically for important intellectual content, gave final approval of the version to be published, and agreed to be accountable for all aspects of the work. a new coronavirus associated with human respiratory disease in china a pneumonia outbreak associated with a new coronavirus of probable bat origin a familial cluster of pneumonia associated with the novel coronavirus indicating person-to-person transmission: a study of a family cluster covid- infection: origin, transmission, and characteristics of human coronaviruses importation and human-to-human transmission of a novel coronavirus in vietnam china coronavirus: cases surge as official admits human to human transmission early transmission dynamics in wuhan, china, of novel coronavirus-infected pneumonia who. coronaviruses (covid- ) . available online at clinical characteristics of hospitalized patients with novel coronavirus-infected pneumonia in wuhan prevention and control strategies for emergency, limited-term, and elective operations in pediatric surgery during the epidemic period of covid- saudi arabia announces first case of coronavirus explaining socioeconomicrelated inequality in knowledge about socio-economic inequality in comprehensive knowledge about hiv in malawi community perception and risk reduction practices toward malaria and dengue: a mixedmethod study in slums of chetla applied business research: qualitative and quantitative methods authority for statistics: the kingdom of saudi arabia size calculator cdc. centers for disease control and prevention: coronavirus (covid- ) . available online at evidence based physical therapy a general anova method for robust tests of additive models for variances a default bayesian hypothesis test for anova designs is the saudi public aware of middle east respiratory syndrome? attitude and practice (kap) study about middle east respiratory syndrome coronavirus (mers-cov) among population in saudi arabia saudi arabia join forces to fight covid- nationally, regionally and globally preventive strategies to keep saudi arabia sars-free awareness, attitudes, and practices related to coronavirus pandemic among public in saudi arabia a lesson learned from middle east respiratory syndrome (mers) in saudi arabia public awareness of coronavirus in al-jouf region, saudi arabia knowledge of middle east respiratory syndrome coronavirus (mers-cov) and its management: a survey among saudi people in taif; kingdom of saudi arabia mers-cov infection: mind the public knowledge gap determinants of health knowledge: an investigation of age, gender, abilities, personality, and interests knowledge, attitudes, and practices towards covid- among chinese residents during the rapid rise period of the covid- outbreak: a quick online crosssectional survey the public's response to severe acute respiratory syndrome in toronto and the united states the impact of community psychological responses on outbreak control for severe acute respiratory syndrome in hong kong a meta-analysis of the association between gender and protective behaviors in response to respiratory epidemics and pandemics the authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.copyright © al-hanawi, angawi, alshareef, qattan, helmy, abudawood, alqurashi, kattan, kadasah, chirwa and alsharqi. this is an open-access article distributed under the terms of the creative commons attribution license (cc by). the use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. no use, distribution or reproduction is permitted which does not comply with these terms. 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- -botshfa authors: abolfotouh, mostafa a.; almutairi, adel f.; banimustafa, ala’a a.; hussein, mohamed a. title: perception and attitude of healthcare workers in saudi arabia with regard to covid- pandemic and potential associated predictors date: - - journal: bmc infect dis doi: . /s - - - sha: doc_id: cord_uid: botshfa background: healthcare workers (hcws) face considerable mental and physical stress caring for patients with covid- . they are at higher risk of acquiring and transmitting this virus. this study aims to assess perception and attitude of hcws in saudi arabia with regard to covid- , and to identify potential associated predictors. methods: in a cross-sectional study, hcws at three tertiary hospitals in saudi arabia were surveyed via email with an anonymous link, by a concern scale about covid- pandemic during – april, . concerns of disease severity, governmental efforts to contain it and disease outcomes were assessed using concern statements in five distinct domains. multiple regression analysis was used to identify predictors of high concern scores. results: a total of hcw responded to the survey. their average age was . ± . years, . % were nurses, . % had direct patient contact, and . % were living with others. the majority of participants ( . %) had overall concern scores of or less out of a maximum score of points, with an overall mean score of . ± . reflecting moderate level of concern. three-fourth of respondents felt at risk of contracting covid- infection at work, . % felt threatened if a colleague contracted covid- , . % felt obliged to care for patients infected with covid- while . % did not feel safe at work using the standard precautions available. nearly all hcws believed that the government should isolate patients with covid- in specialized hospitals ( . %), agreed with travel restriction to and/or from areas affected by covid- ( . %) and felt safe the government implemented curfew and movement restriction periods ( . %). predictors of high concern scores were; hcws of saudi nationality (p < . ), younger age (p = . ), undergraduate education (p = . ), living with others (p = . ) working in the western region (p = . ) and direct contact with patients (p = . ). conclusions: this study highlights the high concern among hcws about covid- and identifies the predictors of those with highest concern levels. to minimize the potential negative impact of those concerns on the performance of hcws during pandemics, measures are necessary to enhance their protection and to minimize the psychological effect of the perceived risk of infection. in december , a cluster of patients with pneumonia was linked to a seafood wholesale market in wuhan, china, which lead to the discovery of a new betacoronavirus [ ] , on january, , named severe acute respiratory syndrome coronavirus- (sars-cov- ) [ ] that causes coronavirus disease . with its novelty and rapid national and international spread on jan , the world health organization (who) international health regulation (ihr) emergency committee declared the disease a public health emergency of international concern (pheic). it was declared by who [ ] as a worldwide pandemic on march . at the time of this writing, it has infected , , individuals, with , , recoveries and , deaths, with an overall estimated case fatality rate (cfr) of . % [ ] . on the nd of march , a saudi citizen coming from iran through bahrain was tested positive for covid- and reported by the ministry of health as the first case in saudi arabia [ ] . as of th june, , saudi arabia had , infected cases, with , recoveries and deaths [ ] . health care workers face considerable mental and physical stress caring for patients with covid- . several reports around the world suggest that this stress has led some physicians to take their own life [ , ] . furthermore, others were overstressed and died from exhaustion [ ] [ ] [ ] [ ] . one approach to minimize such stresses during pandemics is for hospitals to organize physician shifts with mandatory rest and meal breaks. professional societies can also play a significant role by offering online networking to keep doctors connected to provide some level of social support. the government can also play a role by improving the benefits for hcws and their families [ ] . these initiatives can be further enhanced by understanding the level of concerns and worries among healthcare workers and provide targeted strategies that address those concerns. along this line, several studies have investigated the self-satisfaction of hcw and their personal feelings across several important domains [ ] [ ] [ ] [ ] [ ] . these domains cover concerns around risks posed to family members, perception of risk at the work place, and perception of the response of government to the epidemic management [ ] .. understanding the concern level across these different domains can be of importance to targeted mitigation strategies. in saudi arabia, a previous study has shown that hcws had, in general, a negative attitude toward mers-cov infection [ ] . in this study, the majority of the respondents felt that the work environment poses a high risk for contracting the infection and did not feel safe using the standard infection-control measures. one reason for the observed low attitude score might have been the lack of hcw experience with exposure to such outbreaks. due to the potential rapid dissemination of covid- within the public and a large probability of a countrywide outbreak, along with the country's experience in battling this similar coronavirus (mers-cov), the ksa was amongst the leading bodies in the world for its swift community action and hospital preparedness. this study aims to assess perception and attitude of hcws in saudi arabia with regard to covid- , and to identify potential associated predictors. this is a cross sectional study of hcw working at the medical cities of the saudi ministry of national guard health affairs (mng-ha). mng-ha provide healthcare services to national guard service members and their dependents through large medical cities located in the most densely populated regions of ksa, namely the central, western and eastern regions. all facilities have been joint commission international (jci) accredited since . during the covid- , and following the first reported case in ksa, mng-ha has taken drastic infection control measures that included the reduction of elective surgeries, stopping in person outpatient services, and introducing er workflow to minimize covid- cases flow through the main er. the target population of the current study was all hcw employed by the mng-ha at all three regions. an email with an anonymous link to an electronic survey was sent to all hcws who were on duty during the data collection period (~ hcws), across all departments and specialties. this electronic survey was structured using the option that allowed for every participant to participate only once. the target sample size for the survey was estimated assuming a prevalence of high concern among hcw of . % which was observed in another study in the same setting [ ] . we estimated the sample needed for the survey to be participants, assuming % confidence limits and % precision. those who agreed to participate and who responded with completed questionnaires totaled hcws, with a response rate of . %. a structured, self-administered survey of hcws was conducted via email, using a concern scale to assess their concern about covid- pandemic. this survey was designed based on a validated concern scale previously used in a study of the concerns of hcws with regard to mers-cov . the scale consists of statements that cover domains; self-satisfaction, social status, work environment, infection control measures, government action and activities [ ] . the scale was modified to also include a statement about the perception of hcws towards curfew: "i feel safe that government implemented the curfew and the movement restriction periods". a copy of the revised concern scale was attached as a supplementary material. data on gender, age, nationality, marital status, level of education, living status, professional characteristics and contact with patients were collected. hcws were categorized according to their direct contact with covid- patients to "direct contact group", or "non direct contact group". the direct contact group included all subjects caring directly for patients in the er, ward, or icu. all statements were coded using points likert scale, taking values from ("strongly disagree") to ("strongly agree") resulting in a total concern score that ranges from to . participants were further classified into one of three groups based on their total concern score. the first group included subjects below the first quartile of the concern score (score of and below), the second group included subjects with concern score between the th percentile (concern score of ) and th percentile (concern score of ) and the third group included subjects above the th percentile (score of and above) [ ] . the survey was distributed in the english language, as an electronic survey, to all hcws via a link attached to a mass e-mail distribution, with no identifiers. a cover letter was attached to an email as a link sent to hcws in their office emails, during the period between and of april, . study participants were expected to complete the survey and return it back without identifiers. participation in this study was voluntary. hcws were assured in a written informed consent that their responses would remain anonymous and would not affect their performance evaluations, work status or compensations. hcws were asked to respond to the survey if they agree on the informed consent. this study was approved by the institutional review board of the mng-ha in riyadh, saudi arabia (april , ; rc / /r). all categorical variables including age, gender and occupation status were summarized and reported using frequency and proportions. the total concern score was summarized and reported using mean and standard deviation. association of categorical variables with the different levels of concern was analyzed using the chi square test for homogeneity. all continuous variables were compared across the different concern levels using the student-t test and one-way anova. multiple linear regression analysis was used to determine significant predictors of high concern scores to covid- pandemic. for all statistical analyses, significance was considered at a p value of ≤ . . all analyses were performed in the statistical package for the social sciences software (spss version . ; ibm corporation, armonk, ny, usa). a total of mng-ha hcws responded to the survey ( males and females). they had an average age of . ± . years, ( . %) were from the central region, ( . %) from the eastern region and ( . %) from the western region. a total of . % were nurses, . % had direct patient contact, and . % were living with family members and/or others, table . the majority of participants ( . %) had an overall concern score of or less out of a maximum score of points. the responses to the items in the questionnaire varied considerably. with regard to selfsatisfaction domain, responses of concern varied from a high of . % who expressed fear of getting infected from an infected colleague, to a low of . % who felt unconfident a colleague would care for them if they contract the disease. in social status-related domain, concern varied from a high of . % agreeing that they should limit their social activities due to covid- to a low of . % not feeling satisfied of telling their family if they get infected. in workplace-related domain, responses ranged from a high of . % preferring to be absent from work to lower the chance of getting infected to a low of . % agreeing they would feel ashamed telling their managers/colleagues if contracting covid- . in infection control-related domain, responses varied from a high of . % not feeling there was a plan for covid- outbreak in their area to a low of . % did not feel an ic specialist is accessible to respond to their concerns and . % did not feel safe at work when using the standard precautions. in the government-related domain, responses varied from a high of . % agreeing with travel restrictions implemented by the government to a low of . % agreeing that covid- was not discussed efficiently in the media, table . overall, . % of hcws had high concern, . % moderate concern and . % low concern. the average concern score was . ± . , out of a maximum possible concern score of . level of concern was significantly associated with age (χ = . ; p = . ), marital status (χ = . ; p = . ), nationality (χ = . ; p < . ), level of education (χ = . ; p = . ), occupation (χ = . ; p < . ), geographical region of table . in multiple regression analysis ( table ) , predictors of high concern scores were; hcws of younger age (p = . ), saudi nationality (p < . ), undergraduate education (p = . ), and those working in the western region (p = . ), living with others (p = . ) and in direct contact with patients (p = . ). this study aimed to assess perception and attitude of hcws in saudi arabia with regard to covid- , and to table comparison between the levels of concern about covid- and personal characteristics of healthcare workers in saudi arabia characteristics low concern (score = - ) moderate concern (score = - ) high concern (score = - ) total ( identify potential associated predictors. an overall average concern score of . ± . out of a maximum possible score of points was observed, with a negative range of attitude, indicating a moderate level of concern. in comparison with the results of a previous survey in the same settings using the same data collection tool, to assess the concern of hcws about mers outbreak in saudi arabia [ ] , hcws reported significantly higher mean concern scores about covid- pandemic. this may reflect the impact and role of mass media and social media marketing on the way we perceive our world and our everyday lives on individual, social and societal levels, during these critical times. even with the help of the media, this pandemic has had worldwide repercussions and is not yet controlled in some countries. a study was carried out on hcws at king khalid university hospital (kkuh), riyadh, saudi arabia, showed that the majority of hcws had mild anxiety from covid- [ ] . however; the survey was conducted before registering any case of covid- in saudi arabia. an important finding in the present study was that a high level of concern about covid- pandemic was prevalent across the different concern domains. the highest level of concern was observed in the hcws' responses to questions regarding fears of infection of a family member, fears of being in public places that may result in infection, the closure of schools and workplaces in the event of an epidemic and risks associated with dealing with a febrile patient, obligation of care provision for patients infected with covid- and government's action to implement the curfew and the movement restriction periods. it was interesting that in the present study, % agreed that school and shopping markets need to be closed, while only % during the previous mers outbreak [ ] . this finding may reflect the perception of hcws in our study of the magnitude of covid- pandemic. however, it is important to note that this perception of fear might differ from country to another. for example in japan with the absence for an epidemic during the sars-cov outbreak, more than % reported having a high level of fear and an anxiety of infection [ ] , while in thai study, nearly all hcws reported acceptance to take the risk of caring for h n patients [ ] . in line with the who recommendations for institutional preparedness to reduce the impact of potential outbreaks, mng-ha has developed a comprehensive plan of medical and public health response for covid- epidemic [ ] . this plan aimed at the protection of hcws through the implementation of strict infection control measures and personal protection practices. despite these efforts, hcws in our study did not feel safe at the workplace and felt at risk of contracting the infection. this finding is similar to a study in the uk in table comparison between the levels of concern about covid- and personal characteristics of healthcare workers in saudi arabia (continued) low concern (score = - ) moderate concern (score = - ) high concern (score = - ) living condition β beta coefficient, se standard error, t t statistics, *---reference category, **---significant association which % of the hcws did not feel confident in the healthcare system's ability to cope with bird flu epidemic [ ] .. the exact reasons of such high concern among hcws, despite the existence of a preparedness plan, cannot be determined from the current study and further studies are needed. our study shows that hcws who were in direct contact with patients had significantly higher concern scores than those who were not in direct contact. this finding was in agreement with the results of a study in china [ ] to compare the average values of fear, anxiety and depression due to covid- pandemic between medical and admin staff, where medical staff reported greater fear, anxiety and depression than administrative staff. this finding is not surprising given the higher perceived risk by those hcw due to the condition of the work environment. however it is important to pay special attention to those hcws to manage their perception of risk by ensuring that they have access to proper personal protective equipment (ppe) and safe patients' handling procedures [ ] . saudi hcws, in the present study, reported higher concern to covid- pandemic as compared to non-saudis. this can be explained by the culture norms and the difference in living conditions between saudis and non saudi hcw. the majority of non saudi hcw are expats who are likely to live alone with their family memebrs living in their home countries. therfore expats are less likely to worry about the risk of infecting their family members and loved one compared to saudi hcw who live with their families and tend to have a very active social life [ ] .. the present study also showed that living with others was an independent predictor of high level of concern about covid- infection, most likely due to their fear of transmitting the infection to others if they get infected. an interesting but a little counterintuitive finding of our study is the fact that older hcws were less concerned about covid- than the younger ones. this is especially true given that risk factors for severe disease and death in covid- include older age among many other factors [ ] . however, this finding could be attributed to the fact that oldest hcw's could not be working in direct contact to patients, due to the higher risk of severe disease. further, there was a significant association between higher concern score and lower education level. in a survey on the undergraduate medical students in medical institutes of karachi, the majority of students found worrisome of getting infected with covid- during medical rotations, dreaded insufficient care and inappropriate treatment if they acquire infection and thought their institute-associated hospital won't be able to handle the situation in case of an uncontrolled outbreak [ ] . one possible explanation can be inferred from the theory of reasoned action of a causal relationship between knowledge and experience and the subsequent positive perception and intention to change behavior [ ] attitudes and behavioral intent. in the current study hcws of western region had significantly higher concern score compared to other regions. this was different than the study during mers where the hcws of central region had higher concern than other regions [ ] . we believe that these differences are likely due to the perception of hcws of the magnitude of the pandemic in the different regions. during covid- , the western region had shown much rapid increase of confirmed cases compared to the other regions [ ] . additionally, the government has implemented complete lockdown of the western region prior to other regions. however during mers, the largest outbreak has taken place in the central region. the large magnitude of the epidemic the western region compared to other regions in the country could have contributed to the observed level of concern of hcws in this region. our study is not without limitation. our survey was based on self-reported information which might suffer from a recall bias. moreover, all study participants were hcws in tertiary hospitals, and therefore could limit the generalizability of the findings to other settings. finally, all identified predictors of concerns cannot be interpreted beyond general association. despite these limitations, our study addresses a major problem faced by hcws in many countries around the world during this pandemic. the current study highlights the high concern among healthcare workers about covid- and identifies the predictors of those with the highest level of concern. high level of concern could lead to suboptimal healthcare service as well as less effective management of covid- cases. this could be mitigated by implementing strategies designed to minimize perceived risk of infection by hcws. these strategies should be part of the early planning for a response to an epidemic and it should cover a wide range of programs that focus on financial incentives, education, personal counseling and education. supplementary information accompanies this paper at https://doi.org/ . /s - - - . additional file . a novel coronavirus from patients with pneumonia in china clinical features of patients infected with novel coronavirus in wuhan who director-general's opening remarks at the media briefing on covid- - coronavirus covid- global cases by the center for systems science and engineering clinical characteristics of covid- in saudi arabia: a national retrospective study saudi ministry of health dashboard. covid- . accessed th french doctor commits suicide after covid- diagnosis nyc emergency room doctor dies by suicide after treating covid- patients doctors in hubei received more than , consultations in one month. sudden death at home was not identified as a work-related injury hero's award honored for medics who passed away to covid- coronavirus doctor dies of heart attack after working days straight physician deaths from corona virus (covid- ) disease the psychological impact of covid- pandemic on health care workers in a mers-cov endemic country global alert and response: novel mers-cov virus infections state of knowledge and data gaps of middle east respiratory syndrome mers-cov virus (mers-cov) in humans an assessment of the level of concern among hospital-based healthcare workers regarding mers outbreaks in saudi arabia concerns, perceived impact and preparedness in an avian influenza pandemic--a comparative study between healthcare workers in primary and tertiary care awareness, attitudes, and practices related to the swine influenza pandemic among the saudi public sars risk perceptions in healthcare workers impact of knowledge and positive attitudes about avian influenza (h n virus infection) on infection control and influenza vaccination practices of thai healthcare workers world health organization. the world health report -working together for health two thirds of doctors in uk say the nhs could not cope with bird flu epidemic psychological status of medical workforce during the covid- pandemic: a cross-sectional study european centre for disease prevention and control (ecdc)-technical report-infection prevention and control and preparedness for covid- in healthcare settings -third update a closer look at the middle eastern respiratory syndrome (mers-cov) outbreak in saudi arabia covid- : risk factors for severe disease and death concerns of undergraduate medical students towards an outbreak of covid- understanding and promoting aids-preventive behavior: insights from the theory of reasoned action publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations authors' contributions maa contributed to concept development, manuscript preparation and final writing, afa and aab contriputed to concept development and data collection, mah contributed to concept development statistical analysis and manuscript finalization, and afa and aab contributed to research proposal writing, data collection, analysis and interpretation, and manuscript drafting. all authors read and approved the final manuscript. none. most of the data supporting our findings is contained within the manuscript, and all others, excluding identifying/confidential patient data should, will be shared upon request. this study was approved by the institutional review board of the mng-ha in riyadh, saudi arabia (april , ; rc / /r). participation in this study was voluntary. those who agreed to participate signed a written consent form. hcws were assured in a written informed consent that their responses would remain anonymous and would not affect their performance evaluations, work status or compensations. not applicable. the authors declare that they have no competing interests.author details key: cord- -usz pnvu authors: abdel-moneim, ahmed s.; kamel, mahmoud m.; al-ghamdi, abdullhamid s.; al-malky, mater i. r. title: detection of bocavirus in children suffering from acute respiratory tract infections in saudi arabia date: - - journal: plos one doi: . /journal.pone. sha: doc_id: cord_uid: usz pnvu human bocavirus (hbov) was recently discovered in children with respiratory distress and/or diarrhea. to our knowledge, no previous study has reported the existence of bocavirus in saudi arabia. swabs samples from children with respiratory tract infections were examined for the presence of hbov. real-time polymerase chain reaction was used as a sensitive method to detect the hbov. direct gene sequencing was used to determine the genotype of the detected virus isolates. hbov was detected in . % of the examined patients. the np partial gene sequence from all patients showed that the circulated strains were related to hbov- genotype. most of hbov infected patients showed evidence of mixed coinfection with other viral pathogens. the current study clearly demonstrated that genetically conserved hbov circulates in saudi arabia. interestingly, most of the hbov infected cases were associated with high rates of co-infections with other viruses. bocavirus is a single-stranded dna virus belonging to the family parvoviridae, subfamily parvovirinae, genus bocavirus. bocaviruses are unique among parvoviruses because they contain a third orf between the non-structural and structural coding regions [ ] [ ] . the genus bocavirus includes viruses that infect bovine, canine, feline, porcine and some simian species as well as sea lions [ ] [ ] [ ] [ ] [ ] [ ] . human bocavirus (hbov) was first found in children with acute respiratory tract infections in [ ] . it was then detected in children with respiratory tract infections in addition to gastroenteritis worldwide [ ] [ ] [ ] [ ] . the virus exists in four different serotypes hbov - [ ] [ ] [ ] [ ] . although hbov and were reported in respiratory samples, all the genotypes of hbov have been identified in children with acute gastroenteritis. hbov has been reported in various countries, indicating its worldwide endemic nature. the virus has been identified in europe [ ] [ ] [ ] , america [ ] [ ] , asia [ , ] , australia [ ] [ ] , africa [ ] , and the middle east [ ] . the prevalence of hbov ranges between . to . % [ , ] . primary infection with hbov seems to occur early in life and children between the ages of - months seem to be mostly affected [ ] [ ] , but older children can also be infected. newborn children may become protected by maternally derived antibodies [ ] . hbov infections are rarely found in adults [ ] [ ] . lindner et al. detected anti-hbov antibodies in % of healthy blood donors . years of age [ ] . hbov detection has been mostly performed on nasopharyngeal aspirates and swabs and relies mostly on classical [ , , , , , ] and real-time pcr [ , , ] . real-time pcr possesses many advantages over conventional pcr, as it offers greater sensitivity, specificity, and reduced expenditure of time. the current study aims to screen the epidemiological status and molecular phylogeny of hbov isolates prevailing in pediatric patients with respiratory infection in saudi arabia. the current study investigated the prevalence of hbov in patients suffering from respiratory tract infections in saudi arabia. the presence of the major viral causes of the respiratory distress in hbov positive cases was also screened. hbov was detected in / of the examined patients ( . %) with ages ranging from months to years, (table - ). clinical findings for hbovpositive patients were indistinguishable from those for patients with other respiratory viruses. previously, hbov has been detected in samples from patients aged between months and years [ , ] . ma et al, speculated that the antibody against hbov derived from the mother might protect children under months of age from hbov infection [ ] , however, we detected hbov in two cases below months: in a -month-old and -month-old child ( table - ) that may indicate the possibility of hbov infection in very young children. the rate of hbov in respiratory tract infections has been reported to be . to . % [ , ] . real-time pcr was used in the current study to screen hbov due to its high diagnostic sensitivity that could be responsible for the higher rate of hbov infection in saudi arabia than the widely accepted upper limit of infection rates worldwide. meanwhile, a recent study showed . % prevalence among children [ ] . the evidence of hbov as the main initiator of the disease in the infected cases is still uncertain because of its high co-infection rate with other pathogens, and it remains unclear whether hbov is the sole etiologic agent or just a concomitant virus bystander. in previous studies, none of the nasal swabs obtained from healthy children yielded a positive hbov test. this suggests that hbov is not a frequent commensal virus inhabiting the respiratory tract [ , ] . hbov infections are frequently present in concomitant with other viruses and often occur in more than % of the tested samples [ ] . in the current study, only one case was found to be infected only by hbov as a single virus entity while most of isolates ( / ) showed coinfection with other viral pathogens. the most frequently detected co-pathogens were rsv ( / ; . %), iav ( / cases, . %), respiratory adenovirus ( / cases, . %) while only / ( . %) case was coinfected with piv- and none was coninfected with piv- ( table ). it is assumed that the rate and frequency of coinfections may be higher if more viruses were screened. consistent with other studies [ , ] , the prevalence rate of bocavirus was higher in children under years of age (table ) . partial np- gene sequence of the eighteen detected hbov strains were obtained in our study. multisequence analysis showed complete identity ( %) between each other, and phylogenetic analysis demonstrated that they belonged to hbov (data not shown). blast analysis revealed complete homology to the published sequence of hbov . furthermore, the phylogenetic analysis results of three selected sequences showed that the saudi hbov strains obtained from respiratory samples belonged to group i human bocaviruses (fig. ) . to the best of our knowledge, this is the first report of hbov in saudi arabia. continuous surveillance and genome sequence analysis are needed to obtain more information on the genotypic variation and molecular evolution of hbov in the country. the study protocol was approved by the medical ethics review board of the college of medicine, taif university and by the pediatric hospital ethics committee in accordance with the guidelines for the protection of human subjects. informed written consents from the next of kin of the participants involved in the study were taken. nasopharyngeal swabs from children suffered from moderate to severe lower respiratory tract infections were collected from january to may from the governmental pediatric hospital-al-taif, saudi arabia. the children's age ranged from two months to ten years of age. clinical manifestations and case histories were recorded. individual swabs were kept in ml sterile saline containing gentamycin sulphate. swabs were routinely processed and kept at uc until further analysis. the real-time pcr assay was performed using commercial, taqman hydrolysis probe based, real time pcr bocavirus detection kit (liferiver, shanghai, china) in eppendorf master-cyclerh ep realplex . the detection of the amplified amplicon was performed in fluorimeter channel fam with the fluorescent quencher bhq . amplification reactions were performed in a volume of ml containing . ml of dna template, . ml reaction mix, . ml enzyme mix, ml internal control according to the manufacturer's instructions. the thermal cycling conditions were as follows: min at uc, an initial denaturation of min at uc and -cycles of sec at uc and annealing/elongation step of min at uc. hbov positive samples were screened for the presence of respiratory syncytial virus (rsv), influenza a virus (iav), parinfluenza virus (piv- ) and parainfluenza virus (piv- ), as well as respiratory enteric virus (adenv) using real-time pcr kits (shanghai zj bio-tech co., ltd). pcr amplification of a -base pair fragment of the np was performed as described previously [ ] . the reaction mix contained pmol of each primer and dna master mix (koma bioteck, inc., seoul, korea). the thermal cycling conditions were as follows: an initial denaturation of min at uc, cycles of min at uc, min at uc and min at uc, final extension of min at uc.positive pcr products were purified using a qiaquick pcr purification kit (qiagen) and were sequenced commercially (macrogen inc., seoul, korea). the nucleotide sequences of the ns gene were compared with those of hbov strains available at the genbank site. phylogenetic analyses were conducted with mega, version . . the / partial sequences of the ns gene were submitted to genbank (accession numbers jx -jx ). cloning of a human parvovirus by molecular screening of respiratory tract samples human bocaviruses are highly diverse, dispersed, recombination prone, and prevalent in enteric infections virus taxonomy: the eighth report of the international committee on taxonomy of viruses identification and nearly full-length genome characterization of novel porcine bocaviruses identification and characterization of a new bocavirus species in gorillas widespread infection with homologues of human parvoviruses b , parv , and human bocavirus of chimpanzees and gorillas in the wild the fecal viral flora of california sea lions identification and characterization of bocaviruses in cats and dogs reveals a novel feline bocavirus and a novel genetic group of canine bocavirus detection of human bocavirus in japanese children with lower respiratory tract infections epidemiological profile and clinical associations of human bocavirus and other human parvoviruses human bocavirus, a respiratory and enteric virus human bocavirus in children hospitalized for acute gastroenteritis: a case-control study a novel bocavirus associated with acute gastroenteritis in australian children a newly identified bocavirus species in human stool human bocavirus in french children human bocavirus in italian patients with respiratory diseases isolation of human bocavirus from swiss infants with respiratory infections human bocavirus infection human bocavirus infection in young children in the united states: molecular epidemiological profile and clinical characteristics of a newly emerging respiratory virus quantification of human bocavirus in lower respiratory tract infections in china frequent detection of human rhinoviruses, paramyxoviruses, coronaviruses, and bocavirus during acute respiratory tract infections evidence of human coronavirus hku and human bocavirus in australian children human bocavirus in hospitalized children human bocavirus infection among children frequent detection of viral coinfection in children hospitalized with acute respiratory tract infection using a real-time polymerase chain reaction severe pneumonia and human bocavirus in adult surveillance and genome analysis of human bocavirus in patients with respiratory infection in guangzhou, china humoral immune response against human bocavirus vp virus-like particles human bocavirus and acute wheezing in children high prevalence of human bocavirus in infants with lower acute respiratory tract disease in argentina human bocavirus commonly involved in multiple viral airway infections key: cord- -jmoyy rb authors: assiri, abdullah m.; midgley, claire m.; abedi, glen r.; saeed, abdulaziz bin; almasri, malak m.; lu, xiaoyan; al-abdely, hail m.; abdalla, osman; mohammed, mutaz; algarni, homoud s.; alhakeem, raafat f.; sakthivel, senthilkumar k.; nooh, randa; alshayab, zainab; alessa, mohammad; srinivasamoorthy, ganesh; alqahtani, saeed yahya; kheyami, ali; hajomar, waleed husein; banaser, talib m.; esmaeel, ahmad; hall, aron j.; curns, aaron t.; tamin, azaibi; alsharef, ali abraheem; erdman, dean; watson, john t.; gerber, susan i. title: epidemiology of a novel recombinant middle east respiratory syndrome coronavirus in humans in saudi arabia date: - - journal: journal of infectious diseases doi: . /infdis/jiw sha: doc_id: cord_uid: jmoyy rb background: middle east respiratory syndrome coronavirus (mers-cov) causes severe respiratory illness in humans. fundamental questions about circulating viruses and transmission routes remain. methods: we assessed routinely collected epidemiologic data for mers-cov cases reported in saudi arabia during january– june and conducted a more detailed investigation of cases reported during february . available respiratory specimens were obtained for sequencing. results: during the study period, mers-cov cases were reported. full genome (n = ) or spike gene sequences (n = ) were obtained from individuals. most sequences ( of [ %]) formed a discrete, novel recombinant subclade (nrc- ), which was detected in regions and became predominant by june . no clinical differences were noted between clades. among cases reported during february , had no recognized risks for secondary acquisition; of these also denied camel contact. most viruses ( of ) from these individuals belonged to nrc- . discussions: our findings document the spread and eventual predominance of nrc- in humans in saudi arabia during the first half of . our identification of cases without recognized risk factors but with similar virus sequences indicates the need for better understanding of risk factors for mers-cov transmission. middle east respiratory syndrome coronavirus (mers-cov) is known to cause severe respiratory illness in humans, with deaths recorded in %- % of cases reported globally [ ] . since the first recognition of mers in , all cases reported to the world health organization have been linked to the arabian peninsula, with > % of cases reported from saudi arabia [ ] . camels (camelus dromedarius) have been suspected as a reservoir for mers-cov, based on case investigations [ ] , serologic studies [ ] , and the isolation of virus from camels [ ] [ ] [ ] [ ] [ ] . direct camel contact has also been identified as a risk factor for human illness [ ] . secondary human transmission has been demonstrated among close contacts of symptomatic cases, primarily following healthcare-associated exposures [ ] [ ] [ ] and, to a lesser degree, household exposures [ ] . there is no definitive evidence of sustained human-to-human transmission in the community [ ] . mers-cov infection can exhibit a wide range of clinical manifestations, including mild or limited symptoms among those identified through contact tracing [ ] . prolonged viral shedding from the respiratory tract of those without obvious symptoms has been demonstrated [ ] , and transmission related to unrecognized cases has been suggested [ , ] but not documented. mers-cov sequences obtained to date suggest periodic introductions of the virus into human populations, presumably from an animal reservoir, with subsequent limited chains of transmission in households and healthcare settings. the temporal persistence of identified viral clades appears limited, consistent with an r of < [ , ] . intervals between the beginning and end of the circulation of a clade vary, with longer intervals suggesting the existence of undetected human cases [ ] . cases and clusters continue to be reported from countries in or near the arabian peninsula, presenting an ongoing threat for broader transmission [ ] . to assess the epidemiologic and clinical features of the disease, we investigated all cases reported by the saudi arabia ministry of health (moh) during january-june , and we attempted genetic sequencing on all available specimens. this investigation was part of an emergency public health response and was determined to be nonresearch by the moh and centers for disease control and prevention (cdc) and therefore not subject to institutional review board review. at the time of this investigation, reporting in saudi arabia was required for all patients with clinical or radiologic evidence of mers-cov infection and a positive real-time reverse transcription-polymerase chain reaction (rrt-pcr) test result [ ] . all rrt-pcr-positive cases identified at non-moh facilities required confirmation at moh laboratories. we assessed the routinely collected epidemiologic information for all mers-cov cases reported by the moh during january- june , to provide a basic epidemiologic description. for this analysis, we included only individuals who met the case definition described above (ie, symptomatic cases). february was a period of increased reporting. to perform a more in-depth analysis, we collected additional information for all individuals with laboratory-confirmed mers-cov infections during february . this included all cases meeting the case definition as described above, as well as those identified as having a laboratory-confirmed case but no recognized symptoms; individuals not meeting the case definition [ ] were typically identified through contact tracing. we reviewed available moh case investigation records and data reported through the moh health electronic surveillance network. we collected demographic information, medical history, outcome information, and treatment location. we assessed the likelihood of acquisition from another person (secondary acquisition) by determining whether a patient ( ) was a healthcare professional (hcp), ( ) had been admitted to a healthcare facility - days before illness onset, ( ) had visited any healthcare facility in the days before illness onset, or ( ) had direct contact with either another documented case of mers-cov infection or with someone with an acute respiratory illness of unknown cause in the days prior to illness. when it was not possible to determine the criteria described above by using available information, we conducted telephone interviews (in arabic) to collect additional exposure information. proxies (a close friend or immediate family member who was familiar with the patient's activities during this period) were interviewed if the case was deceased, still hospitalized, or too ill to participate. among cases without any of the aforementioned risk factors for secondary acquisition (hereafter referred to as sporadic cases), we asked during telephone interviews about the history of exposure to camels [ ] . interviewees were prompted to describe examples of camel exposures, including direct contact or visiting a live market, slaughterhouse, or race where camels were present. we also assessed travel history. demographic and clinical characteristics were reported, and differences were assessed for significance by using χ , wilcoxon rank sum, and kruskal-wallis tests, where appropriate. data were analyzed using sas, version . (sas institute, cary, north carolina). molecular testing was performed on all respiratory specimens available during january-june . specimens and molecular testing at the moh respiratory specimens, including nasopharyngeal and oral pharyngeal swabs, both separate and combined, nasopharyngeal and tracheal aspirates, and sputa collected from suspected mers cases were tested at moh laboratories by upe and orf a rrt-pcr assays [ ] . available specimen aliquots (or rna extracts) that tested positive for mers-cov by both assays were shipped on dry ice to the cdc (atlanta, georgia) for sequencing. sample aliquots ( - µl, if available) were extracted on a nuclisens easymag (biomerieux), and µl of total nucleic acid elutes were recovered. the specimen extract were retested by mers-cov n and/or n rrt-pcr assays [ ] , and sequencing was attempted on confirmed positive samples. overlapping nested primer sets were used for amplification and sanger sequencing of the mers-cov spike genes and selected genomes (supplementary table ). amplicon sequencing was performed in both directions, using sequencing and internal amplification primers, with the bigdye terminator v . cycle sequencing kit on a xl genetic analyzer (thermo fisher scientific). sequencher . software (gene codes) was used for sequence assembly and editing. nucleotide sequences were aligned using clustal x, version . , implemented in bioedit, version . . . phylogenies were estimated using neighbor-joining and maximum likelihood methods implemented in molecular evolutionary genetics analysis, version . [ ] , and bayesian inference, using mrbayes v . . [ ] . the neighbor-joining method used maximum composite likelihood distance estimation and maximum likelihood used general time reversible (gtr) model of nucleotide substitution with γ-distributed rate variation and a proportion of invariant sites (gtr + g + i). mrbayes was performed under a gtr model of nucleotide substitution with categories of γ-distributed rate heterogeneity and a proportion of invariant sites (gtr + + i). putative recombination events were identified using recombination detection program software, version . (rdp ; available at: http://web.cbio.uct.ac.za/~darren/rdp.html), with the default settings [ ] . the complete genome sequence of each of the viruses in the nrc- clade was aligned with the genomes outside the clade. the multiple sequence alignment was then imported into the rdp software for detection of recombination. the software uses several algorithms, including gene-conv, bootscan, maxchi, chimaera, siscan, and seq, to detect putative recombination events. the potential minor and major parental sequences and the beginning and end breakpoints of the potential recombinant sequences were also defined by rdp software. putative recombinant events were considered significant when a p value of ≤ . was observed for the same event, using ≥ algorithms. time estimates to the most recent ancestor were calculated using the bayesian markov chain monte carlo (mcmc) method implemented in beast v . . [ ] . the coding regions (orf ab, s, orf , orf a, orf b, orf , e, m, and n) in the genomes grouping within nrc- were concatenated, and the hky+ Γ substitution model was used with independent rates for each of the positions in the codon. a lognormal relaxed molecular clock (uncorrelated) was used with gaussian markov random field bayesian skyride coalescent. bayesian mcmc analysis was run for million steps. parameters for tmrca, rate, and trees were sampled every steps, with the first % removed as burn-in. time estimate values thus obtained were also compared with strict and exponential relaxed clock models. during january- june , mers-cov cases from of the regions of saudi arabia were reported by the moh; mers-cov-positive individuals with no recognized symptoms, and who therefore did not meet the case definition, were not included. the longest period between case reports was days. among these cases, were hospitalized, and ( %) died. most patients were male ( [ %]) and of saudi nationality ( [ %]). median age was years (range, - years). of the symptomatic cases reported during the study period, had respiratory specimens available for further testing at the cdc; specimen was also available from an individual with no recognized symptoms who did not meet the case definition. of the available respiratory specimens collected during january- june , spike gene sequences were obtained from (supplementary table table ). recombination analysis on the newly available genome sequences from nrc- identified possible recombination events involving sequences from outside the clade as potential minor and major parental strains. the first event had a predicted breakpoint at nucleotide position ( % confidence interval [ci], - ), located in orf ab, and the second event had a predicted breakpoint at ( % ci, - ), located in the spike gene. recombination analysis was performed using rdp software, and events detected with a p value of ≤ . were considered evidence of true recombination (supplementary table ). to date the emergence of nrc- , mcmc analysis was performed on the concatenated coding regions of the genomes grouping within nrc- , using beast. the most recent common ancestor of the virus was approximately . years table ). among the cases reported during january- june , nrc- was first detected in a case with onset in mid-january (figure a) . during the study period, nrc- viruses were detected in regions of saudi arabia (figure ) , and the proportion of patients identified with nrc- increased steadily over time ( figure b ). nrc- was next compared to past and present subclades within clade b, using sequences available in genbank (figure ). nrc- was more widely distributed geographically than any other identified members of clade b. the duration of circulation of recognized subclades ranged from to days. at the conclusion of our investigation period, nrc- had been circulating for days, which was longer than of other identified subclades. in our analysis, the longest circulating subclade reported was riyadh_kkuh- _ , which was first detected in july and was still circulating as of may . during our investigation period, of sequenced viruses belonged to riyadh_kkuh- _ . no viruses belonging to clade a were detected. a comparison of patients infected with nrc- versus other circulating viruses revealed no significant differences in age, sex, rate of mortality, time between onset of symptoms table ). there was also no difference in mean cycle threshold values, a proxy for virus load, with respiratory specimens containing nrc- versus other clades, although these were not adjusted for timing of specimen collection (supplementary table ). for our more detailed analysis of cases reported during - february , we identified mers-cov-positive patients ( table ). of these, patients ( %) satisfied the case definition for routine reporting and required hospitalization; the remaining individuals ( %) had no recognized symptoms (and did not satisfy the case definition) but are included in this analysis. the patients were reported from different healthcare facilities across regions in saudi arabia; of these facilities reported ≥ cases within the same -day period. of these patients, sequences could be obtained from , of which ( %) were associated with nrc- . no clinical differences were apparent when comparing nrc- to other circulating viruses ( table ) . the patients with laboratory-confirmed disease reported during february were also classified according to their reported exposures during the weeks before illness onset. record review and interviews were conducted during - march . among the cases, were classifiable using information obtained by the initial case investigation. interviews were attempted for the remaining patients. of these, ( %) were interviewed; individual refused to participate, and patients were not available. proxy interviews were conducted for of interviews, including for patients who were deceased and for of patients who survived. among the patients, ( %) were determined to have had household contact with a confirmed mers-cov case, ( %) were hcps, ( %) were inpatients in a healthcare facility, ( %) were hospital visitors, and ( %) were unable to be classified owing to a lack of available information (table ) . notably, patients ( %) denied exposure to a healthcare facility or to a person with acute respiratory illness in the weeks before illness onset and were classified as sporadic cases (tables and ); among these, individual reported visiting a camel farm in the weeks before illness onset. among the sporadic cases, were available for interview, and were interviewed by proxy. among the interviewed by proxy, were deceased and were too ill to participate in the interview. sequences were obtained for sporadic cases, and ( %) were nrc- , including the individual who had visited the camel farm. in the republic of korea [ , ] , thailand (accession number kt ), and china in [ , ] . previous documentation of the duration of circulation in humans of different mers-cov clades in saudi arabia during - noted an average detection time of days [ ] . in contrast, we demonstrate that nrc- has persisted longer than most previously documented clades. nrc- was found to eventually predominate over the -month study period and attain a wide geographic distribution in a comparatively short period. while this apparent emergence and clade displacement is suggestive of greater epidemiologic fitness [ ] , we observed no clinical differences between nrc- and other clades; the implications for virus replication and transmission need further study. during preparation of this manuscript, sequences obtained from camels in oman in may [ ] and saudi arabia during july -april [ ] were reported that showed similar recombination features and phylogenetic association with nrc- . in camels, nrc- (referred to as lineage [ ] ) was first detected in july and became predominant in saudi arabia during a period that overlaps with our study, corroborating our findings of an increased prevalence in humans relative to other clades. recombination has been documented among covs [ ] and has been linked to the emergence of more-pathogenic strains of some animal covs [ ] [ ] [ ] . evidence of intraspecies recombination has also been found with the human covs hku [ ] , nl [ ] , oc [ ] , and, more recently, mers-cov [ ] . genome analysis of human mers-cov strains from saudi arabia in and the recent outbreak in south korea/china [ ] [ ] [ ] and camels as noted above [ , ] revealed a probable signature recombination event between different parental clade b viruses involving a region of the orf ab and spike genes. we confirmed this finding and documented an increasing prevalence of this virus in humans among samples collected since january from geographically distant communities in saudi arabia. similar to recent reports [ ] , we estimate that this recombinant virus emerged sometime in mid-to-late . based on recently available sequence data from camels in saudi arabia, nrc- (lineage ) was predicted to have diverged between december and june [ ] . in our study, further analysis of patients with laboratoryconfirmed mers-cov reported in february revealed individuals with no recognized risks for secondary acquisition; none of these reported direct camel contact, although individual reported visiting a camel farm. of those sequenced, most were infected with genetically very similar viruses, suggesting a potential for limited transmission from those with unrecognized mers-cov infection. these findings highlight the importance of strengthened epidemiologic and laboratory surveillance. most cases identified in saudi arabia in february had documented exposure to healthcare facilities, a well-demonstrated risk factor for mers-cov infection [ ] [ ] [ ] . seventeen of affected facilities in saudi arabia in february experienced mers-cov infection clusters. moreover, of patients in february ( %) were visitors to healthcare facilities. this is similar to the jeddah outbreak, where % of investigated cases were visitors [ ] . recommendations to limit visitation in facilities with ongoing mers-cov transmission should be reinforced to limit these exposures. our investigation, which was performed as part of an emergency public health response, is subject to several limitations. first, specimens were not available for all cases during the study period, meaning that many viruses remained untyped; however, we observed no demographic differences between cases who had specimens sequenced and those who did not. second, since its emergence in , surveillance and sequencing of mers-cov strains has been incomplete; variations in sequence availability and documentation might have influenced the extent of persistence and geographic spread that we have determined for past circulating virus strains. case definitions, testing practices, and testing locations have also changed during this period. third, although we were able to obtain full genome sequences from nrc- samples, all of which possessed the expected recombinant signal, our sequencing was mostly limited to the spike gene alone, which poses the risk of misclassifying recombinant viruses as belonging to nrc- . this is illustrated in the recent study by sabir et al [ ] , which reported multiple novel recombinant viruses in camels, including recombinants between nrc- (lineage ) and other virus clades. fourth, because of the high morbidity and mortality of mers-cov infection, interviews with cases were not always possible, necessitating the use of proxies. it is possible that, combined with issues of recall, the quality of the information collected varied. of particular consideration, of sporadic cases were classified on the basis of interviews with proxies, and pre-illness exposures might not have been accurately recognized and reported. fifth, some camel exposures may have gone unrecognized because of disincentives for reporting camel exposures, given their cultural and economic significance in saudi arabia. sixth, given the existing evidence of association between mers-cov illness and pre-illness healthcare exposure or exposure to sick individuals [ , , ] , our risk classification was hierarchical; that is, reported exposure to a setting where secondary acquisition was likely took precedence over reported exposure to camels. as such, we did not assess camel exposures in individuals with recognized risks for secondary acquisition. finally, although we have attempted to link the results of our epidemiologic investigation with mers-cov sequences obtained from investigated cases, we cannot fully assess the possible role of virus introductions from nonhuman sources. recent phylogeny of mers-cov sequences from camels in saudi arabia indicated that the novel recombinant subclade (referred to as nrc- in our manuscript) was also predominant in camels during a period overlapping with our study [ ] . as such, our detection of closely related viruses in humans might in part reflect multiple introductions from camels with similar strains. virus introductions from other currently unidentified sources might also be factor. virus transmission dynamics within and between human and nonhuman sources of mers-cov will likely influence transmission routes in ways not yet fully understood. this investigation describes the emergence, persistence, and widespread circulation of a novel recombinant mers-cov in saudi arabia. a lack of clearly defined epidemiologic links in some cases highlights the need for ongoing intensive epidemiologic and laboratory surveillance to better understand mers-cov transmission and to focus infection prevention and control efforts. supplementary materials are available at http://jid.oxfordjournals.org. consisting of data provided by the author to benefit the reader, the posted materials are not copyedited and are the sole responsibility of the author, so questions or comments should be addressed to the author. potential conflicts of interest. all authors: no reported conflicts. all world health organization. summary of current situation, literature update and risk assessment middle east respiratory syndrome coronavirus in dromedary camels: an outbreak investigation middle east respiratory syndrome coronavirus neutralising serum antibodies in dromedary camels: a comparative serological study evidence for camel-to-human transmission of mers coronavirus middle east respiratory syndrome coronavirus (mers-cov) in dromedary camels isolation of mers coronavirus from a dromedary camel mers coronaviruses in dromedary camels human infection with mers coronavirus after exposure to infected camels, 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 multifacility outbreak of middle east respiratory syndrome in taif, saudi arabia family cluster of middle east respiratory syndrome coronavirus infections world health organization. who statement on the ninth meeting of the ihr emergency committee regarding mers-cov a case of long-term excretion and subclinical infection with mers-coronavirus in a health care worker a family cluster of middle east respiratory syndrome coronavirus infections related to a likely unrecognized asymptomatic or mild case interhuman transmissibility of middle east respiratory syndrome coronavirus: estimation of pandemic risk transmission and evolution of the middle east respiratory syndrome coronavirus in saudi arabia: a descriptive genomic study spread, circulation, and evolution of the middle east respiratory syndrome coronavirus world health organization. who statement on the tenth meeting of the ihr emergency committee regarding mers case definition and management of patients with mers coronavirus in saudi arabia assays for laboratory confirmation of novel human coronavirus (hcov-emc) infections real-time reverse transcription-pcr assay panel for middle east respiratory syndrome coronavirus mega : molecular evolutionary genetics analysis version . mrbayes: bayesian inference of phylogenetic trees rdp : detection and analysis of recombination patterns in virus genomes bayesian phylogenetics with beauti and the beast . preliminary analysis of middle east respiratory syndrome coronavirus (mers-cov) sequences from korea and china evolution patterns of the middle east respiratory syndrome coronavirus (mers-cov) obtained from mers an observational, laboratory-based study of outbreaks of middle east respiratory syndrome coronavirus in jeddah and riyadh, kingdom of saudi arabia complete genome sequence of middle east respiratory syndrome coronavirus (mers-cov) from the first imported mers-cov case in china complete genome sequence of middle east respiratory syndrome coronavirus kor/knih/ _ _ , isolated in south korea origin and possible genetic recombination of the middle east respiratory syndrome coronavirus from the first imported case in china: phylogenetics and coalescence analysis viral fitness: definitions, measurement, and current insights asymptomatic mers-cov infection in humans possibly linked to infected camels imported from oman to united arab emirates co-circulation of three camel coronavirus species and recombination of mers-covs in saudi arabia recombination, reservoirs, and the modular spike: mechanisms of coronavirus cross-species transmission emergence of pathogenic coronaviruses in cats by homologous recombination between feline and canine coronaviruses emergence of a group coronavirus through recombination importation and recombination are responsible for the latest emergence of highly pathogenic porcine reproductive and respiratory syndrome virus in china coronavirus diversity, phylogeny and interspecies jumping genomic analysis of colorado human nl coronaviruses identifies a new genotype, high sequence diversity in the n-terminal domain of the spike gene and evidence of recombination molecular epidemiology of human coronavirus oc reveals evolution of different genotypes over time and recent emergence of a novel genotype due to natural recombination mers-cov recombination: implications about the reservoir and potential for adaptation acknowledgments. we thank shifaq kamili, for logistics of specimen shipment; and laura wright of the centers for disease control and prevention (cdc) geospatial research analysis and services program.disclaimer. the findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the cdc.financial support. this work was supported by the saudi arabia ministry of health and the cdc as part of an emergency response. in the weeks before becoming ill, none had known contact with a patient with mers, a person with severe respiratory illness, and anyone mildly ill, and none reported working in or visiting a healthcare facility.abbreviations: g, full genome sequence obtained; s, spike region sequence obtained; ns, not sequenced. a genbank accession number. key: cord- - bqzf zw authors: cheema, ejaz; almualem, abdulmohsin abdulaziz; basudan, abdulmohsen talal; salamatullah, abdulaziz khalid; radhwi, sohaib omar; alsehli, ammar soliman title: assessing the impact of structured education on the knowledge of hospital pharmacists about adverse drug reactions and reporting methods in saudi arabia: an open-label randomised controlled trial date: - - journal: drugs ther perspect doi: . /s - - -z sha: doc_id: cord_uid: bqzf zw background: pharmacists have limited knowledge about adverse drug reactions (adrs) in saudi arabia. objective: the aim of this study was to assess the impact of educational intervention on the knowledge of hospital pharmacists about adrs. methods: this was a -month randomized controlled trial conducted in saudi arabia between january and march . participants in both groups were required to complete an online questionnaire at baseline and at -week follow-up. participants in the intervention group received a structured information sheet about adrs weeks after the first assessment. the main outcome measure was difference in mean knowledge score about adrs. main outcome measure: difference in mean knowledge score about adrs. results: a total of participants were included in the study. at the -week follow-up, there was a significant improvement in the mean knowledge score (± standard deviation) of intervention participants from . (± . ) at baseline to . (± . ) ( % ci − . to − . ; p < . ). the mean knowledge score of control participants remained unchanged at . (± . ) during both baseline and follow-up assessments. conclusion: adr-specific education was associated with a significant improvement in the knowledge and understanding of pharmacists about adrs and their methods of reporting. electronic supplementary material: the online version of this article ( . /s - - -z) contains supplementary material, which is available to authorized users. adverse drug reactions (adrs) are associated with significant morbidity and mortality worldwide [ ] . a study conducted to determine the number of adr-related emergency hospital admissions in england reported an increase in adr-led admissions from . % in to . % in [ ] . in saudi arabia, the frequency of adr-related hospital admissions was reported to be . per admissions and . per patient days [ ] . an adr is defined by the medicines and healthcare products regulatory agency (mhra) as "an unwanted or harmful reaction experienced following the administration of a drug or a combination of drugs under normal conditions of use and which is expected to be related to the drug" [ ] . spontaneous reporting systems are the most important pharmacovigilance activity used worldwide by healthcare professionals to report any suspected adrs that may not have been identified during premarketing clinical trials [ ] . pharmacists are also expected to play an important role in electronic supplementary material the online version of this article (https ://doi.org/ . /s - - -z) contains supplementary material, which is available to authorized users. ensuring medicine safety by detecting and reporting adrs. hospital pharmacists, in particular, are ideally placed to report adrs due to their access to patients' medical records and frequent interactions with prescribers. in the year , the saudi food and drug authority (sfda) established a national pharmacovigilance centre (npc) with the aim of reporting and detecting adrs [ ] . the npc expects all healthcare professionals, including doctors, pharmacists and nurses, to report adr,s and have introduced both paper and online systems to facilitate adr reporting. however, despite the availability of paper and online methods of adr reporting, adrs continue to be under-reported by healthcare professionals in saudi arabia [ ] . the under-reporting of adrs could be partly attributed to the lack of awareness and understanding of adrs by healthcare professionals in saudi arabia. a cross-sectional study conducted to assess the knowledge of pharmacists about adrs in saudi arabia reported inadequate knowledge and understanding about pharmacovigilance [ ] . more than half of the participants of the study, including pharmacists, doctors and nurses, were not even aware of the correct definition of pharmacovigilance. similar findings of limited awareness about pharmacovigilance and adr reporting by healthcare professionals have been reported in another study conducted in saudi arabia [ ] . given the poor knowledge of healthcare professionals about adrs and its impact on adr reporting, this study aims to assess the impact of structured education on the knowledge of hospital pharmacists about adrs and their reporting methods in saudi arabia. this study was a -month randomized controlled trial conducted in the makkah region, saudi arabia between january and march . the study had two groups; eligible participants were subsequently randomized to either a control or an intervention group. the randomization and allocation sequence were conducted by an independent person who produced a computer-generated randomized list. this person was not involved in the recruitment or enrolment of the participants. participants were enrolled in the study by the members of the research team. both groups were then followed up for months to see the difference in the mean knowledge score about adrs and their methods of reporting. qualified hospital pharmacists from all ethnic backgrounds working in the in-patient or out-patient settings in the private or government hospitals were eligible for the study. eligible participants were identified and approached by the members of the research team. exclusion criteria included community pharmacists, pharmacy students and pharmacy technicians, as well as pharmacists working in the pharmaceutical industries and academia. a -item questionnaire was developed using the format and style of a questionnaire used in a previous study [ ] . specific questions were included about the methods of adr reporting in saudi arabia. the questionnaire was piloted on a sample of six pharmacy students. the section "background" had five items that explored the demographic information of participants (see appendix in the electronic supplementary material for the questionnaire). the section "methods" comprised two main items, each having six items that aimed to gather information about the types of adrs that should be reported by pharmacists in children and adults. the section "results" consisted of two items that were designed to assess the awareness of pharmacists about the methods of reporting adrs in saudi arabia. the maximum possible score was and the minimum was . the questionnaire was developed in the english language. participants in both groups were assessed at baseline and the -week follow-up. participants in the intervention group electronically received a double a -sized information sheet containing structured advice on adrs and their methods of reporting. this information was developed by a team of six researchers using the guidance produced by the sfda and was sent to the participants two weeks after the first assessment. at the same time, a separate double a -sized information sheet containing information about the coronavirus was also sent electronically to the control participants. based on the findings of a previous study [ ] , it was expected that % of the participants will be aware of the methods of adr reporting in saudi arabia. using a sample size calculator (raosoft), the sample size calculation indicated that a sample size of participants per group will provide a power of % at the % level in a -tailed test to detect an increase in the participants' awareness about methods of adr reporting from to %. questionnaire responses were coded, and data was analysed using spss version . data was single-entered. paired t test was used to compare the mean knowledge score of the participants within the group (at baseline and followup) and un-paired t test was used to compare the score between the two groups. a total of participants were invited to take part in the study. of these, participants agreed to take part and were included in the study (response rate %); see fig. for the flow of participants through the study. at baseline, no statistically significant differences were found between the demographics of participants in the intervention and the control groups (table ) . at the -week follow-up, there was a significant improvement in the percentage of participants who were familiar with the types of adrs that should be reported in adults (section of the questionnaire in supplementary material) in the intervention group (from at baseline to %; % ci . - . ; p = . ). there was a non-significant improvement in the percentage of control participants from % at baseline to . % at the follow-up for the same questionnaire item ( % ci − . to . ; p = . ). similarly, there was a significant improvement in the percentage of intervention participants who were familiar with the types of adrs that should be reported in children from . % at baseline to % at follow-up ( % ci . - . ; p = . ). however, the percentage of control participants did not improve significantly ( % at baseline to % at the follow-up) ( % ci − . to . ; p = . ) for the same questionnaire item. with regards to the awareness about methods of adr reporting (section of the questionnaire in supplementary material), a significant improvement was reported in the awareness of intervention participants from . % at baseline to . % at the follow-up ( % ci . - . ; p = . ) as comparted with control participants who only reported a non-significant improvement from . % at baseline to % at follow-up ( % ci − . to . ; p = . ). at the -week follow-up, there was a significant improvement in the mean knowledge score (± standard deviation) of intervention participants from . ± . at baseline to . ± . ( % ci − . to − . ; p < . ). the mean knowledge score of control participants remained unchanged at . ± . during both baseline and follow-up assessments. to the authors' knowledge, this is the first rct that has assessed the impact of adr-specific education on the knowledge of hospital pharmacists about adrs and the methods of reporting them in saudi arabia. this study reported that participants declined to participate fig. flow of participants through the study provision of adr-specific education was associated with a significant improvement in the mean knowledge score of intervention participants compared with the participants in the control group. furthermore, the educational intervention also led to a significant increase in the awareness of pharmacists about methods of adr reporting. similar findings have also been previously reported in a cluster rct that reported a significant improvement in adr reporting by pharmacists who received an educational programme about pharmacovigilance and adrs [ ] . provision of structured and written education on adrs to participants in the intervention group was associated with a significant improvement in their knowledge about the types of adrs that should be reported in adults (from to %) and children (from . to %) as opposed to control participants who only showed a non-significant improvement in their knowledge. although considerable improvement was reported in the knowledge of intervention participants, a majority of the participants (around %) failed to correctly identify the types of adrs that should be reported in adults and children. a majority of the participants did not consider it important to report mild reactions from a drug with a black triangle in adults during both pre-and postintervention assessments. as far as reporting of adrs in children was considered, reporting of mild reactions from an existing drug was not considered to be important by most of the pharmacists who completed the study. one of the possible reasons that may explain such a misconception by intervention participants about adr reporting is that perhaps they needed further reminders about adrs and the types of adrs that should be reported in both adults and children. it is important to highlight that participants in the intervention group only received the educational intervention once at the start of the study and did not receive any further education during the rest of the study period. with regards to the awareness of participants about the methods of adr reporting, a majority (∼ %) were only aware about the online method of reporting prior to receiving educational intervention. following the provision of adr-specific education, more than half ( %) of the participants were reported to be aware of both paper-based and online methods of adr reporting. awareness of control participants about adr reporting methods remained largely unchanged between baseline and follow-up assessments of the study. the effectiveness of the educational intervention in improving the mean knowledge score of pharmacists about adrs underscores the importance of providing explicit education to pharmacists about adrs at both undergraduate and practice level. topics related to pharmacovigilance are not given due share in the curricula offered by the majority of institutions offering medicine, pharmacy or nursing programmes in saudi arabia [ ] . this could be explained by the lack of availability of enough qualified staff trained in pharmacovigilance and medication safety in saudi arabia [ ] . the npc, therefore, needs to make efforts to introduce the concept of pharmacovigilance to healthcare professionals working in the hospital settings by organizing specific educational seminars and workshops. hospital pharmacists by virtue of their regular contact with patients together with access to medical records are ideally placed to report suspected adrs and should therefore be encouraged to improve their adr reporting. provision of continuous professional development programmes to pharmacists can help address their knowledge gaps in adr detection and further improve adr reporting. the aim of such programmes should not only be to improve pharmacists' understanding about adrs, but should also focus on changing their attitudes and perceptions toward adr reporting. furthermore, core topics related to pharmacovigilance should be included in the curricula offered by the academic institutions to enhance the knowledge of healthcare students about adr reporting. this study was limited by using non-validated information sheets that were delivered to study participants. furthermore, participants could not be blinded to the study intervention owing to the nature of educational interventions. nevertheless, this study has several strengths. it was a well-designed rct that was informed by prior evidence. a sample size calculation was undertaken prior to the study. exclusion and inclusion criteria were rigorously applied to ensure that the study population was representative of the target population. participants were randomly allocated to the study arms through a set of computer-generated numbers to minimize selection bias. the findings of this study suggest that adr-specific education can improve the knowledge and understanding of pharmacists about adrs and their methods of reporting. future work should focus on the development of effective instruction methods that deliver pharmacovigilance education to healthcare professionals with the aim of improving their adr reporting in saudi arabia. adverse drug reactions in hospital inpatients: a prospective analysis of patient-episodes trends in emergency hospital admissions in england due to adverse drug reactions incidence of adverse drug events in public and private hospitals in riyadh, saudi arabia: the (adesa) prospective cohort study mhra. adverse drug reactions under-reporting of adverse drug reactions: a systematic review pharmacovigilance system in saudi arabia pharmacist's awareness and knowledge of reporting adverse drug reactions in saudi arabia attitude, knowledge and experience of hospital pharmacists with pharmacovigilance in a region in saudi arabia: a cross-sectional study barriers to reporting of adverse drugs reactions: a cross sectional study among community pharmacists in united kingdom improving the reporting of adverse drug reactions: a cluster-randomized trial among pharmacists in portugal we would like to thank all individuals who participated in the study. ethics approval the study was approved by the institutional review board of umm-al-qura university (uqu-cop-ea# ). funding this study did not receive any funding.informed consent participants were provided written information about the study and its aims. the completion and submission of the anonymised online questionnaire by the participants was taken as their consent to the study. key: cord- - g cvwt authors: al-khani, a. m.; khalifa, m. a.; almazrou, a.; saquib, n. title: the sars-cov- pandemic course in saudi arabia: a dynamic epidemiological model date: - - journal: nan doi: . / . . . sha: doc_id: cord_uid: g cvwt objective: saudi arabia ranks second in the number of coronavirus disease (covid- ) cases in the eastern mediterranean region. it houses the two most sacred religious places for muslims: mecca and medina. it is important to know what the trend in case numbers will be in the next - months, especially during the hajj pilgrimage season. methods: epidemiological data on covid- were obtained from the saudi arabian ministry of health, the world health organization, and the humanitarian data exchange. a susceptible-exposed-infectious-recovered (seir) prediction model was constructed to predict the trend in covid- in saudi arabia in the next months. findings: the model predicts that the number of active cases will peak by may . the cumulative infected cases are predicted to reach , at that time. the total number of infected individuals is estimated reach to , by the end of the pandemic. conclusion: our estimates show that by the time the hajj season commences in saudi arabia, the pandemic will be in the midst of its deceleration phase (phase ). this information will likely be useful to policymakers in their management of the outbreak. since late december , the world has been experiencing a rapidly spreading, highly infectious virus, the severe acute respiratory syndrome coronavirus (sars-cov- ). the world health organization (who) declared this new disease a "public health emergency of international concern" on january and then as a "global pandemic" days later ( ) . current knowledge suggests that respiratory droplets are the primary mode of transmission. less than % of all active coronavirus disease (covid- ) cases are asymptomatic, which is lower than that of influenza ( - % asymptomatic) ( ) . within the eastern mediterranean region, the kingdom of saudi arabia ranks second only to the islamic republic of iran in total number of infected and active cases ( ) . saudi arabia has a population of million, the majority ( %) of whom dwell in several major cities: riyadh, mecca, jeddah, dammam, and medina ( ) . the majority of covid- cases are concentrated within these cities. as of may , there were , total cases in saudi arabia, , recoveries and deaths ( ) . the healthcare system of saudi arabia is no stranger to coronavirus outbreaks, having dealt before with local outbreaks of middle east respiratory syndrome coronavirus (mers-cov) ( ) . the first covid- case (n= ) in saudi arabia was detected in the eastern region (i.e., qatif) on march nd; it was an individual who had traveled to the endemic region of iran. the qatif area was put on lockdown within three days of the first case. the government took decisive measures to control potential outbreaks by cancelling festivals and events, suspending e-visa entry, and halting all domestic travel by march th . the following day, all educational institutions were closed. public gatherings and weddings were banned a week later. on march th , all arriving and departing international flights were cancelled, followed on march th by the prohibition of daily prayers in mosques, including the weekly friday prayer. transportation between cities was banned soon after on march st ( ) . to mitigate virus transmissions that occur from gatherings, saudi authorities have enforced a -hour curfew in major cities (riyadh, medina, jeddah, mecca, and dammam) since april th , while the rest of the country has been under limited curfew (from pm to am) since april th ( ) . it announced a -day nationwide -hour curfew from may rd to may th to curb the tide of the epidemic ( ) . saudi arabia houses the two most sacred religious places for muslims: mecca and medina. they make pilgrimage to these cities either at a fixed time (i.e., hajj) or at any time (i.e., umrah) in a calendar year. during the current pandemic, saudi authorities have stopped umrah pilgrimage, effectively reducing imported sars-cov- cases ( ) . furthermore, hajj has been put on hold this year due to the overwhelming infection rate of sars-cov- ( ) . since , saudi arabia has faced multiple outbreaks during hajj seasons, including the h n pandemic ( ) , multiple local mers-cov outbreaks ( ) , and ebola and zika viruses from african pilgrims ( , ) . the literature has suggested hajj pilgrims played a key role in the dispersion of the flu pandemic ( ) . infectious disease prediction models are tools that use available data about the status and progress of an infectious outbreak to predict its future course ( ) . in its most basic form, an infectious disease prediction model is constructed of three essential compartments: ) susceptible (s), ) infected (i), and ) recovered (r), commonly abbreviated as the sir model. the addition of a fourth compartment, i.e., exposed (e), increases the prediction capability of the resultant model (i.e., seir), which is now being widely used ( ) . there are practical implications for predicting the epidemiological trajectory of the covid- in saudi arabia as the country is still in the midst of this outbreak. a prediction can inform the country's decision makers and help them make prudent decisions about the continued management of the outbreak. the saudi healthcare system can also utilize this information to adapt to changing health needs. meanwhile, we can hope to maintain a controlled situation until vaccines and treatments are deployed. we name our prediction model ksa-cov- , and with it, aim to find the following: ) the anticipated epidemic curve of sars-cov- in saudi arabia, ) the peak, the end, and the number of covid- cases associated with the curve, and ) the timing of upcoming hajj (july th -august nd ) in relation to the anticipated epidemic curve. the data used to generate our ksa-cov- model were obtained from three different sources: ) the saudi arabian ministry of health ( ) , ) the who ( ) , and ) the humanitarian data exchange ( ) . the three databases were cross-checked against each other for accuracy and as a sensitivity measure. while all data sources provided an identical reporting of the number of confirmed, recovered and death cases, none of them provided any daily updates in respect to the number of quarantined (i.e., exposed) cases. a recent report from the centers for disease control and prevention found that for positive cases, close-contact individuals were identified ( ) . we used this information to estimate the number of the exposed compartment in the model. . cc-by-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . . https://doi.org/ . / . . . doi: medrxiv preprint a deterministic compartmental model (dcm) with a susceptible-exposed-infectiousrecovered (seir) disease class was chosen to be implemented in the ksa-cov- model. for this model to work, a number of assumptions/variables needed to be inputted. firstly, there were parameters that characterize the disease: ) the basic reproduction number (r ), ) the duration of the exposed state (e.dur), ) the duration of the infectious state (i.dur), and ) the case fatality rate (cfr). secondly, the population parameters at the start of the modeling were also inputted: ) number of susceptible (s.num), ) the number of exposed (e.num), ) the number of infected (i.num), and ) the number of recovered (r.num). building on the work of peng et al., a new compartment (p) was included in our model that conveyed the increased level of public health awareness, such as widespread face masks, strict social distancing, and the locking-down of cities ( ) . we assumed that the susceptible population (s) was declining at a steady rate as a result of a positive protection rate (α); the number of those protected (p compartment, p.num) is removed from the susceptible pool (s.num). in this paper, we present four models: ksa-cov- model, two variants of ksa-cov- model, and a natural course model (table ). the parameters chosen for these four models are justified below. . cc-by-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . . different parameters used to generate the epidemiological models of the covid- . natural we assumed that our model is based on a closed system (i.e., s+p+e+i+r= million, the total population of saudi arabia) ( , ) , and that deaths in the population are solely due to covid- . in our model, we did not use parameters related to the birth and death rate among . cc-by-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . . https://doi.org/ . / . . . doi: medrxiv preprint the susceptible, exposed, infectious, and recovered, in line with the methodology used in similar studies ( ) . we chose march nd , the day on which the first positive case (i.e., diagnosed) of covid- was documented, to be the starting date of our prediction model. in the absence of definitive data, we assumed that the first diagnosed case exposed the average people. in their report, sanche et al. estimated the median r value of sars-cov- to be . ( % ci . - . ) ( ) . thus, the ksa-cov- model integrated an r value of . . furthermore, other reports found that the average incubation period of sars-cov- was . days ( ) , which we have used as the e.dur in our model. ( ) . therefore, a conservative period of days was inputted as the duration of the infected state (i.dur) in the ksa-cov- model (table ) . we used a -day duration to generate another model (model , table ). the aforementioned parameter estimates (i.e., e.dur, i.dur) have been previously used in other seir models ( ) . in regards to the death rate among those infected, although the who states that the global mortality rate of covid- is approximately . % ( ) , in saudi arabia, a rate of . % was calculated by averaging the death rate from when the first death case was recorded until april . we used this rate ( . %) in all four models that we present. after trial and error, we chose an α (protection rate) value of . for our model. this value produced a prediction line that most closely fit the observed cases in saudi arabia so far. as a sensitivity measure, we used values reported by other studies that have utilized a similar methodology. for example, in their original report, peng et al. ( ) used a value of . , so we used that to generate another model (model , table ). . cc-by-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . . https://doi.org/ . / . . . doi: medrxiv preprint finally, we generated a model that simulated the natural course or "free fall" of the sars-cov- virus in saudi arabia. this model assumes that people were mixing at random and that no preventive measures were taken to halt the progression of the infection (natural course model, table ). the analytic component of this paper was carried out using the epimodel ( ) package in the r statistical programming language, version . . (r foundation for statistical computing). microsoft excel was used for data storage and management. in this paper, we generated four different models that provided an estimation for the covid- course in saudi arabia. a summary of the models is shown in fig. . . cc-by-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . . https://doi.org/ . / . . . doi: medrxiv preprint is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . . cc-by-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . . https://doi.org/ . / . . . doi: medrxiv preprint is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . . the rapid evolution of the covid- situation worldwide and in saudi arabia makes it extremely challenging for healthcare systems to adapt. this paper predicts the course of the pandemic in the coming months in saudi arabia. we predict that the effects of the covid- will have peaked during the third week of may . availability of epidemiological modeling of the novel corona virus in the middle east is scarce. indian researchers recently predicted that covid- cases would peak between the third and fourth weeks of april in india, when they would reach , confirmed cases ( ) . recent reports have stated that the current forecasts project a continuing increase with large uncertainty ( ) . our mathematical model has several strengths. for example, data used in the modeling were obtained from three different sources and checked for accuracy. additionally, this model incorporated a susceptible-exposed-infectious-recovered (seir) mathematical model, which is more favorable than a susceptible-infectious-recovered (sir) one. on the other hand, one limitation of this study is that the accuracy of the predictions only lasts for a few weeks to months due to the erratic behavior of the current corona virus. similarly, the accuracy of this prediction is highly correlated with how accurately and effectively new cases are recorded; it is vital to note that the number of identified infected cases will largely depend on the implemented testing strategy (i.e., how many tests are done in the population). as of may th , saudi arabia had done , tests, which is equal to approximately one test per people ( ) . additionally, our ksa-cov- model overestimates the number of recovered cases, but the number of recovered cases in saudi arabia has been increasing rapidly. for instance, in a period between may and may , the number of recoveries increased -fold, and by may th , the number of recovered cases had . cc-by-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted june , . . surpassed the number of active cases by a large margin ( ) . finally, despite utilizing previously published estimates for the average incubation period (e.dur) and average infection duration (i.dur), the model still undershoots the amount of active infection due to the rapid flow from the infected (i) compartment to the recovered (r) compartment of the seir model. in conclusion, this ksa-cov- model is one of the few and early prediction models in saudi arabia and the middle east. our estimates show that by the time the hajj season commences in saudi arabia, the pandemic will be in the midst of its deceleration phase (phase ), during which the danger of the pandemic will be declining, but exceptional care should be taken to avoid a resurgence. strict adherence to the current control measures is essential to maintain the predicted pattern, and caution should be taken when easing these measures because deviation may adversely alter the predicted course. the final decision on whether to hold the hajj pilgrimage this year should take the findings of this study into consideration. . cc-by-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted june , . . https://doi.org/ . / . . . doi: medrxiv preprint updates on coronavirus disease: world health organization asymptomatic ratio for seasonal h n influenza infection among schoolchildren in taiwan coronavirus disease (covid- ) situation reports: world health organization the general authority for statistics -saudi arabia: the general authority for statistics gastat covid dashboard: saudi arabia: ministry of health (saudi arabia) the critical care response to a hospital outbreak of middle east respiratory syndrome coronavirus (mers-cov) infection: an observational study covid- in the eastern mediterranean region and saudi arabia: prevention and therapeutic strategies the ministry of interior: a -hour curfew in riyadh saudi arabia announces -hour curfew for eid al-fitr holiday journal of travel medicine. . . saudi official urges muslims to delay hajj plans over virus. usnews public health. pandemic h n and the travel implications of emerging coronaviruses: sars and mers-cov. travel medicine and infectious disease under the shadow of global zika spread the hajj in the time of an ebola outbreak in west africa. travel medicine and infectious disease clinical respiratory infections and pneumonia during the hajj pilgrimage: a systematic review. travel medicine and infectious disease mathematical modelling of infectious diseases susceptible exposed infected recovery (seir) model with immigration: equilibria points and its novel coronavirus (covid- ) cases data: humanitarian data exchange active monitoring of persons exposed to patients with confirmed covid- -united states epidemic analysis of covid- in china by dynamical modeling the effect of control strategies to reduce social mixing on outcomes of the covid- epidemic in wuhan, china: a modelling study high contagiousness and rapid spread of severe acute respiratory syndrome coronavirus incubation period of novel coronavirus ( -ncov) infections among travellers from wuhan, china clinical presentation and virological assessment of hospitalized cases of coronavirus disease in a travel-associated transmission cluster. medrxiv. . . who director-general's opening remarks at the media briefing on covid- epimodel: an r package for mathematical modeling of infectious disease over networks outbreak trends of coronavirus (covid- ) in india: a prediction. disaster medicine and public health preparedness forecasting the novel coronavirus covid- the authors thank ms. erin strotheide for her editorial contributions to key: cord- -uf i x authors: altuwaijri, fahad s.; ferrario, maria angela title: investigating agile adoption in saudi arabian mobile application development date: - - journal: agile processes in software engineering and extreme programming - workshops doi: . / - - - - _ sha: doc_id: cord_uid: uf i x mobile app development has been considered as one of the fastest growing segments of the software industry both worldwide and in saudi arabia. due to their pervasiveness, mobile applications call for consideration of complex and rapidly changing requirements given the diversity of their environments. therefore, agile is considered the most suitable methodology for developing mobile apps. however, little research has investigated agile adoption in mobile app development in the real context. therefore, the purpose of this phd is to investigate the factors that have a significant impact on agile adoption in mobile app development by small and medium-size software organisations in saudi arabia. the expected key contribution of this research will be a deep insight into agile adoption in mobile app development, and the design and development of tools and techniques that may support agile adoption within saudi context. the aim of this phd research is to investigate the factors influencing agile adoption in mobile application development sector in saudi arabia. mobile app development has been considered as one of the fastest growing segments of the software industry both worldwide [ ] , and in saudi arabia [ ] with mobile devices now becoming integral parts of our lives across domains such as health, entertainment, education and marketing. due to their pervasiveness and ubiquity, mobile applications call for careful consideration of complex and rapidly changing requirements given the diversity of the environments of their use in terms of user experience, user interface, and reception quality [ , ] . although there have been several studies that concluded that agile is a natural fit for mobile app development [ ] [ ] [ ] [ ] , there is a need for empirical evidencebased research that investigates the specific factors (e.g. cultural, technical and environmental) that support or challenge the agile adoption in mobile app development by small and medium-size software organisations. to the best of the author's knowledge, there are no studies about that in middle eastern countries, particularly in saudi arabia. in the following subsections, the research aims and objectives are presented as well as the research questions. section briefly summarises the related work. the research methodology design is provided in sect. , covering a description of each step of the research process. section discusses the validity threats. the last section outlines the current status of my phd and some future works. this research aims to investigate the key factors that can either support or hinder agile adoption in mobile app development by software organisations in the kingdom of saudi arabia. it is intended that the key research contribution will be twofold: ( ) a deeper insight into agile adoption in saudi mobile app development; and ( ) the development of tools and techniques that support agile work in saudi arabia. these aims will be achieved through the following objectives: the main research questions that motivated this research are: rq . what are the types of factors that support or hinder agile adoption in mobile app development in the context of saudi arabian software organisations? the main research question is divided into four sub-research questions: it is important to investigate the facilitating factors and the challenges related to the adoption of agile principles and practices in developing software projects. this is because such understanding will help determine to what extent agile can be adopted and how it influences the success of projects. in this regard, scholars have advocated that the suitability of agile adoption by software organisations depends on the practitioners'cultural background, hence, agile is dependent on several human factors [ , ] . studies have found that practitioners' culture, communication, skills and experiences are considered as the most important factors that influence the adoption of agile [ , ] . furthermore, organisational aspects are considered as one of the most significant aspects of agile adoption [ , ] . on the other hand, chow and cao [ ] argued that besides the importance of organisational and people aspects, technical factors have a significant impact on agile adoption, including the agile software techniques and delivery strategies. all of the studies mentioned above advocate that the practice of agile is mainly influenced by human factors. this means that people or organisations in different countries practice agile differently according to their cultural differences. therefore, this research will investigate the factors identified in previous studies to determine whether they can be considered as the main aspects affecting the adoption of agile in saudi mobile app development. although there are numerous studies that focused on identifying the factors influencing agile adoption [ , , ] , there is a lack of studies on the adoption of agile in middle eastern countries, particularly its adoption in mobile app development in saudi arabia. with regards to investigating agile adoption in mobile app development, several studies have focused on identifying the benefits and challenges of the adoption and discussing the proposed agile-based mobile methodologies such as mobile-d [ , ] . however, these studies did not investigate the factors influencing agile adoption in mobile app development. the initial step in investigating the factors influencing agile adoption by software organizations is to examine practitioners' awareness and perceptions of agile. several research efforts about this topic, however, most of these studies were conducted in developed countries such as [ ] [ ] [ ] and only a handful were conducted in the context of developing countries such as brazil [ ] , paraguay [ ] and india [ ] . unfortunately, none of these studies is focused on agile perceptions and usage in mobile app development in the middle eastern countries, especially saudi arabia. in the context of saudi arabia, bin-hezam et al. [ ] studied to what extent agile has been adopted by smes in saudi arabia. this study was applied to different enterprises (i.e. technical and non-technical) and did not target mobile software organisations. some existing research examined the awareness and perception on a global scale. an example is the work of begel and nagappen [ ] who investigated that among microsoft employees. on the other hand, even though this study was considered global because the data was collected from three continents (i.e. north america, asia and europe), it only concentrated on one company that has similar aspects across the world. therefore, to the best of the author's knowledge, there has been no study about the level of awareness among saudi mobile app developers towards agile, the reasons for agile adoption and non-adoption from their point of view, their perceptions towards agile methods and the tools and techniques used to support their agile teams and their limitations. the design of this research will be explorative and inspired by interdisciplinary research framework [ ] , which is agile, people-focused and reflective. using an agile approach in managing our phd research will help us move forward quickly and reflectively through the research process. hence, the results from each study will be used to inform and shape the subsequent studies of the research. this research is divided into three cycles, which are explained below and summarised in fig. . each cycle will last for - months and involves three iterative stages (i.e. plan, act and reflect). in each cycle, there are several sprints each of which will last for - weeks. the first cycle: formative and piloting. this cycle aims to study the current related work and to understand the current usage and perception of agile in saudi arabia. expert interviews will be conducted to take the experts' viewpoint about the perception of agile and take their opinions before designing next studies. in addition, a survey questionnaire will be conducted to identify the awareness and perception of software development in general, particularly agile among saudi mobile app developers who either adopt or do not adopt agile methods. the second cycle: design and development. this cycle aims to conduct in-depth investigation to obtain a deep insight into the key factors that may influence agile adoption in saudi mobile app development and the tools and techniques used. this investigation will be achieved through three data collection methods (i.e. interviews, observation and a focus group). the results of each activity will be used to inform and shape the next one. in addition, a prototype of tools or techniques that can support agile team within saudi context will be designed and developed. if there are certain tools and techniques that widely acceptable in agile in western context, but may not be suitable in saudi context, we will investigate what mechanisms could support the outcome of these tools and techniques in saudi context. the third cycle: analysis and evaluation. this cycle aims to analyse and evaluate the factors and tools, as well as to conclude the writing up of the thesis. a questionnaire will be utilised in this study to analyse the relationships between variables with a statistical technique (i.e. factor analysis). in terms of the tools and techniques developed, they will be evaluated based on the interviews with the agile team members who will use them. the data collected from the quantitative methods will be analysed using a statistical software (i.e. spss). this will determine the relationships and trends in the data and illustrate them through graphs and cross-tabulated formats. in addition, factor analysis (fa) will be used to analyse the relationships between variables [ ] . with regards to the data collected from qualitative methods, nvivo software will be used for organising and coding the data. in addition, the data will be subjected to the approach of thematic analysis that helps in developing themes and patterns from the data collected [ ] . the validity threats are discussed in this research to explain how to reduce these threats. using the empirical research method, i will reduce my bias by applying mixed research methods as different data collection methods will be used. a pilot test for each data collection method will be conducted to avoid the threat of having questions that can be hard to understand by the participants. in terms of the research context, the study will not be limited to a specific software organisation and data will be collected from different teams from different organisations to represent organisations throughout saudi context. furthermore, my supervisor has strong experience in empirical research methods, thus, she could be a reference point to ensure the validity of the study. this research is still in the early phase, thus, we have not started the fieldwork yet. several tasks have been completed over the last months. first, we have reviewed the current literature. second, we have designed the research methods that will be used throughout this research. third, we have contacted mobile app developers in saudi arabia to participate in our study, and they agreed to collaborate with us. finally, we have designed the first empirical study (i.e. expert interviews) that is seeking approval from the ethics committee. the next step will be conducting expert interviews. a survey questionnaire will be designed and shaped based on the finding of the expert interviews to the awareness and perceptions of agile. after that, we will begin to investigate the key factors influencing agile adoption through empirical research. an empirical study of investigating mobile applications development challenges unlocking the digital economy potential of the kingdom of saudi arabia challenges and best practices for mobile application development: review paper software engineering issues for mobile application development software development processes for mobile systems: is agile really taking over the business? applying agile methodology in mobile software engineering: android application development and its challenges mobile app development and management: results from a qualitative investigation a survey study of critical success factors in agile software projects identifying some important success factors in adopting agile software development practices agile software development: the people factor agile transition and adoption human-related challenges and issues: a grounded theory approach people over process: key challenges in agile development the relationship between organizational culture and the deployment of systems development methodologies usage and perceptions of agile software development in an industrial context: an exploratory study strengths and barriers behind the successful agile deployment-insights from the three software intensive companies in finland survey on agile and lean usage in finnish software industry the evolution of agile software development in brazil concerns and limitations in agile software development: a survey with paraguayan companies a survey on agile practices in the indian it industry is the agile development method the way to go for small to medium enterprises (smes) in saudi arabia? in: st software engineering for 'social good': integrating action research, participatory design, and agile development discovering statistics using ibm spss statistics thematic analysis and code development key: cord- - e ajbgq authors: alhabdan, yazeed abdullah; albeshr, abdulhameed ghassan; yenugadhati, nagarajkumar; jradi, hoda title: prevalence of dental caries and associated factors among primary school children: a population-based cross-sectional study in riyadh, saudi arabia date: - - journal: environ health prev med doi: . /s - - -z sha: doc_id: cord_uid: e ajbgq background: dental caries is a preventable childhood disease, but public health efforts are hampered due to limited information on associated factors in vulnerable populations. our study was aimed at estimating the prevalence of dental caries and identifying key associated factors in four major risk domains, including socioeconomic factors, child oral health behavior and practices, child feeding practices, and dietary habits among primary school children in saudi arabia. methods: a cross-sectional study design was used to recruit male saudi primary school children, aged – years, from primary schools in five different regions of riyadh. children were clinically screened to detect carious lesions in primary teeth according to world health organization’s criteria. structured self-administered questionnaire was used to collect information on social and individual factors from the parents. the odds ratios and % confidence intervals of associated factors for dental caries were computed using logistic regression models; key factors were identified by systematic selection process that accounted for multicollinearity and bias correction. results: dental caries was prevalent among children ( %, % confidence interval . – . %). individual factors, including irregular brushing, late adoption of brushing habit, consulting dentist for symptomatic treatment, lack of breast feeding, sleeping with a bottle in mouth, habit of snacking between meals, low consumption of fruits, and frequent consumption of soft drinks and flavored milk, were predominantly associated with dental caries in children, instead of socioeconomic factors (p < . , adjusted r-square %). conclusion: dental caries were prevalent in school children, and individual factors were predominantly associated with the disease. electronic supplementary material: the online version of this article ( . /s - - -z) contains supplementary material, which is available to authorized users. dental caries is a major oral health problem affecting . billion people ( . % of the population) worldwide in the year [ ] . a high burden of dental caries was evident among children in saudi arabia with an estimated prevalence of approximately % [ ] ; other high-risk areas include latin america, middle east, and south asia [ ] . the world health organization (who) emphasizes the need to reduce global burden of dental caries in attaining optimal health. consequently, in the year , who and fédération dentaire internationale (fdi) world dental federation set global goals for oral health in to guide planners and policy makers to improve the status of oral health in their populations [ ] . unfortunately, knowledge gaps with respect to the availability of baseline data on oral health and population-specific key modifiable factors of dental caries restrict the ability of many developing nations and semi-developed countries, including saudi arabia to attain the goals set by who. in addition, competing interests in health care funding warrant prioritizing the associated factors to better direct public health mitigation efforts. although factors, such as occupational status, family income, and level of education of parents [ ] [ ] [ ] [ ] [ ] that affect the socioeconomic status of populace, have been associated with dental caries, their relative impact on dental caries compared to individual factors is unclear. moreover, modification of socioeconomic factors requires time-consuming macro level changes. in contrast, individual factors, such as child oral health behaviors, child feeding practices, and dietary habits that play a role in cariogenesis, could be targeted for modification by directing the limited resources to primary school children. prior evidence illustrates the importance of adopting good oral health behaviors such as regular brushing of teeth, using mouthwash, and flossing teeth in reducing the disease burden and attaining optimal oral health [ ] . similarly, the role of sugary foods (e.g., candies) in cariogenesis was also well established [ ] . however, the relative significance of aforementioned oral behavioral factors on cariogenesis compared to other host factors could vary significantly in different populations owing to cultural and behavioral practices. in our globalized world, constant migration of individuals and transfer of certain behaviors or practices (e.g., favoring flavored milk over plain milk among children) [ ] is the prevailing norm. therefore, the knowledge of associated factors for dental caries in saudi children not only benefit saudi populace but also international organizations such as who and health authorities in directing the mitigation efforts at vulnerable populations (e.g., children). this study aimed at estimating the prevalence of dental caries in primary teeth and identifying key associated factors in - -year-old school children in riyadh city of saudi arabia would contribute towards the knowledge of dental caries by enriching the baseline data and determining population-specific risk factors of such a highly prevalent and preventable condition. our analysis is the first in saudi arabia to comprehensively evaluate and prioritize factors encompassing all four major risk domains for dental caries, including parental socioeconomic status, children oral health behavior and practices, child feeding practices, and dietary habits. in addition, the relative importance of individual factors (over socioeconomic factors) as determinants of dental caries was assessed using extensive modelling techniques. a population-based cross-sectional study design was employed to determine the burden of dental caries in primary teeth and key associated factors among - -year-old male primary school children recruited from government primary schools for boys located in geographical regions (southern, northern, eastern, western and central) in riyadh city, saudi arabia. the study included only saudi nationals, whose parents were able to fill the self-administered questionnaire and provide informed consent for their child's dental examination at school. non-saudi children or children with non-saudi care givers or parents were excluded. this study was conducted in the year between september and november . sample size was calculated using single proportion formula based on % confidence level, expected prevalence of % [ ] , precision of . , and design effect of . the recommended sample size was children with one of their parents as a single unit. we anticipated low response rate owing to the outbreak of middle east respiratory syndrome-corona virus (mers-cov) in riyadh city during the study period. therefore, a total of questionnaires were distributed to parents and we received completed questionnaires at a response rate of % from out of schools considered for recruitment among government primary schools for boys in riyadh region. our study sample was obtained by a multistage random sampling technique. briefly, up to three primary schools in riyadh were randomly selected from each of the five geographical locations in riyadh city based on the list of primary schools obtained from the ministry of education. a maximum of students were randomly selected from each of these schools. each of the five regions in riyadh city contributed a fifth of the total study sample. children underwent a simple dental examination based on the world health organization diagnostic criteria for oral health surveys [ ] . the basic oral assessment of every child was performed by a single, well-trained professional dentist by seating each subject on a chair in a good day light using mouth mirror and dental probes. this simple oral examination poses no harm to children. the intra-examiner reliability was good based on re-examination of children prior to the study (kappa value = . ). caries status in the crown of primary teeth was assessed using decayed (d), missing (m), and filled (f) teeth (dmft) index [ , ] ; teeth missing (m) or filled (f) contributed to the overall dmft score only if they were missing or filled because of caries. a dmft score above null indicates the presence of caries, whereas a null score indicates the absence of caries [ ] . a structured self-administered parental questionnaire was developed by relying on previous studies [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] and accounting for cultural sensitivities of the study population. the questionnaire was translated into arabic and then back to english to ensure accuracy. face validity, feasibility, and construct validity of the questionnaire was established prior to study. the questionnaire responses provided data on age of the child, demographic and socioeconomic factors such as father's education level, mother's education level, parental occupation as health care provider, monthly income of the family, region of residence, type of residence, and availability of medical insurance with dental coverage. parents also provided information on oral health behavior and practices of children, such as frequency of brushing teeth with toothpaste in a day; age at which children started brushing; use of dental floss; use of mouthwash; frequency of fluoride application; recent visit to the dentist; habit of eating after brushing teeth in night; and child feeding practices, such as type of milk feeding practice (breast-fed only/children mixed-fed with both breast milk and powdered milk/powdered milk only), age of child when breast feeding was stopped, age of child when bottle feeding was stopped, child sleeping with bottle in mouth, number of meals per day, number of snack items consumed between meals, and snack time corresponding to main meals (ate snacks with main meals only/ate snacks in between main meals or with main meals). dietary information included use of multivitamin supplementation (no/yes) and consumption of fresh fruits, fresh vegetables or salads, fast food, candy, potato chips, sweetened chewing gum, fresh juice, flavored juices, soft drinks, fresh milk, and flavored milk at least twice a week (no/yes). some of the original variable categories were combined to create meaningful new groups, and facilitate appropriate analyses. in particular, the 'frequency of brushing teeth' variable was classified in to categories (children brushing less than once daily/once daily/two times or more daily. all analyses of study data were performed using sas software version . (sas institute inc., cary, nc, usa). categorical variables were described as counts and percentages, whereas means and standard deviations (sd) were computed for continuous variables. the % confidence intervals for proportions were constructed using clopper-pearson exact tests. the independence of characteristics of study sample by caries status (presence or absence) was assessed using pearson's chi-squared test (or fisher's exact tests for smaller samples) and p values. missing data were analyzed as a separate category (unknown or other) in corresponding variables. the main associated factors for dental caries in our study were determined in three steps. in the first step, the association between each characteristic of study sample and the presence of dental caries was evaluated using univariate logistic regression analyses; all the variables that were significant at p value less than or equal to . were selected for second step of analyses. in the second step, the associated factors for dental caries among each of the four broader determinants of health, including socioeconomic factors, child oral health behavior and practices, child feeding practices, and dietary factors, were identified based on four separate stepwise logistic regression analyses. subsequently, the covariates that were significant (p ≤ . ) in each of the four analyses were selected for further analysis. in the final step, a stepwise multivariate logistic regression analysis was performed on covariates selected from step two and variable age group of the child ( or or years) to determine key associated factors for dental caries. in addition, multicollinearity was assessed using collinearity indices, eigenvalues, and variable decomposition proportions for all the multivariate models. one of the highly collinear variables was removed giving precedence to children oral health behavior and practice covariates. in addition, firth's bias correction was applied to the final multivariate model to address potential issues due to small sample size, and complete or quasi-complete separation. the measures of association were reported as unadjusted odds ratios (uor) and adjusted odds ratios (aor) along with their corresponding % confidence intervals ( % ci). the discrimination, calibration and overall performance of the final multivariate model was assessed using concordance statistic, hosmer and lemeshow goodness-of-fit test, and adjusted cox and snell r-square, respectively. the performance of final model with and without socioeconomic factors was compared based on adjusted cox and snell r-square, which indicates the proportion of variation explained by the covariates in the model. statistical analyses that yielded a p value less than or equal to . were considered significant. a total of primary school boys aged to years in riyadh, saudi arabia, were analyzed in this study. the prevalence of dental caries in our sample was % ( % ci . - . %). about % ( % ci . - . %) of children had no carious lesions. the age-specific prevalence of dental caries among children aged , , and years was . % ( % ci . - . %), . % ( % ci . - . %), and . % ( % ci . - . %), respectively. the mean age and dmft score in our sample was . (sd ± . ) and . (sd ± . ), respectively. table provides the frequencies, percentages, and differences (by caries status) for various characteristics of study population. a significant number of fathers ( . %, % ci . - . %) and mothers ( . %, % ci . - . %) did not attend a college or university, and their children experienced high prevalence of dental caries. majority of the children came from low-income families ( . %, % ci . - . %), and approximately % of them experienced dental caries. most of the study subjects lived in rental homes, and % had no dental coverage in medical insurance. in general, the children had poor oral health behavior and practices as most of them started brushing at a late age ( or more years) and brushed less than once daily ( %) in any given week. the use of dental floss and mouthwash was negligible, and most of the children visited a dentist for symptomatic treatment. although the practice of breast feeding is common, most of the children were weaned by the first year. the practice of mixed feeding was common in our sample; approximately % of mixed-fed children experienced dental caries compared to % of children that were exclusively fed with either breast milk or powdered milk. the practice of sleeping with a bottle in mouth and frequent consumption of sugary snacks between meals was also common. the consumption of fresh fruits and fresh juice was less prevalent in our sample. the summary of variables selected during different steps of selection process is illustrated in table . barring few exceptions, almost all the factors were significantly associated with dental caries' experience in univariate analyses (step ). in the ensuing step multivariate analysis, a limited number of factors were associated with dental caries in each of the four risk domains with more concessions observed among dietary factors. in the final step of model selection, the highly collinear child feeding covariate (i.e., age of the child when breast feeding was stopped) was excluded to address multicollinearity. our model selection process yielded variables that were significant at p < . for inclusion in the final model. although association measures were not provided in table to avoid confusion, interested readers could find these details in additional file . the unadjusted and adjusted odds ratios along with their % confidence intervals (based on firth's bias correction) for the variables, representing all four risk domains, in the final model are reported in table . it should be noted that factors representing low socioeconomic status, such as low level of maternal education, low family income, and lack of dental insurance, were associated with a minimum of fourfold increased dental caries experience. child oral health practices, such as failure to brush teeth at least once a day, failure to start brushing on or before a child attained years of age, and visiting dentist for symptomatic treatment, were associated with dental caries experience in children. children habituated to sleeping with bottle in mouth experienced . -fold higher dental caries compared to children not practicing this habit (aor = . , % ci . - . ). in addition, lack of mixed feeding and consuming two or more sugary snack items between meals were predominantly associated with dental caries experience (p < . ). dietary habits, such as less consumption of fresh fruits and frequent consumption of soft drinks and flavored milk, were significantly associated with dental caries with an odds ratio of . , . , and . , respectively. the final model was well calibrated (p = . ; hosmer and lemeshow goodness-of-fit test) with very high discriminatory power (c-statistic = %) and high overall performance (adjusted r-square of %). subsequent exclusion of three variables representing socioeconomic status from the final model also resulted in a well-calibrated model (p = . ; hosmer and lemeshow goodness-of-fit test) with very high discriminatory power (c-statistic = %). however, a slight reduction in overall performance from to % was noted, signifying the influence of individual or personal factors (represented in the remaining three risk domains) on dental caries experience in children; the overall performance of model with variables representing socioeconomic status was %. in addition, the higher magnitude of adjusted odds ratios of individual factors (ranging from . to . ) compared to aors of socioeconomic factors (ranging from . to . ) and the lower confidence limits that were consistently above . lend further support to the predominant flavored milk x x x *the variables selected in the step were marked with an "x," and variable excluded is marked as "-." the variables selected were significant at p value less than or equal to . †the variable "age of the child when breast feeding was stopped" was excluded to address the issue of collinearity in the final model influence of individual factors on dental caries' experience in children. dental caries was prevalent among -to -year-old primary school children in saudi arabia ( %, % ci . - . ). we identified individual factors, encompassing three major risk domains (children oral health behavior and practices, child feeding practices, and dietary habits) that were predominantly associated with dental caries' experience in our study. especially, child oral health behavior and practices, such as brushing teeth at least once daily, starting the practice of brushing earlier than years, and visiting a dentist regularly, were significantly associated with dental caries. in addition, children mixed-fed with both breast milk and powdered milk, children sleeping with bottle in mouth, and the practice of snacking two or more items between meals were linked to dental caries experience in children. dietary habits, such as less frequent consumption of fresh fruits (once a week or less) and more frequent consumption of soft drinks and flavored milk (more than once a week), were significantly associated with dental caries in our study. in our sample, socioeconomic factors (less-educated mothers, low family income, and lack of dental insurance coverage) were less influential than individual factors in determining dental caries' experience in - -year-old male primary school children. the high prevalence of dental caries observed among primary school children in our sample was consistent with previous studies in saudi arabia [ , [ ] [ ] [ ] [ ] and uae [ ] . a recent meta-analysis of various dental caries studies in different regions of saudi arabia determined the prevalence to be % [ ] . furthermore, the observed prevalence of dental caries among children in the present study was substantially higher than the target established for the year ( %) by who/fdi [ ] . the collective evidence from our study and previous studies confirm the endemic nature of dental caries in middle eastern population and signify the burden on public health. it is interesting to note that dental caries' experience among primary school children was better explained by individual factors ( %) rather than socioeconomic factors ( %) in our study, which is consistent with weaker role of socioeconomic factors observed in developed nations [ , ] . this notion was further supported by the relatively stronger associations observed between individual factors and dental caries experience in our study. in contrast, several cross-sectional and longitudinal studies from developing nations demonstrated the dominant role of socioeconomic factors in dental caries' experience [ , [ ] [ ] [ ] . the risk profile of dental caries among children in saudi arabia appears to follow the theme in developed world, where oral health behavioral practices and dietary habits were relatively more important [ ] . however, efforts directed at improving socioeconomic status should be continued, owing to evidence from the present study and prior studies that identified maternal education and family income as consistent associated factors for dental caries [ , , , ] . in addition, the availability of dental coverage in medical insurance was associated with dental caries. although literary evidence was inconsistent in saudi arabia [ ] , the alarming proportion of children ( %) that lacked dental coverage in medical insurance warrant further attention. our results were consistent with previous studies on dental caries that reported an association between dental caries and good oral health behaviors in general [ , ] , and tooth brushing habits in particular [ , ] . a recent meta-analysis identified a . -fold higher risk of dental caries among people brushing less than once daily compared to those brushing regularly (odds ratio (or) = . ; % ci . - . ) [ ] . an overwhelming majority of children started brushing after years ( %, % ci . - . %) in the present study, consistent with late adoption of brushing observed in previous studies in saudi arabia [ , ] and in philippines [ ] . however, the higher risk of dental caries observed uniquely among children who started brushing late at or years, in our sample, warrant further investigation. particularly, future studies could evaluate the possible table unadjusted odds ratios (uor), adjusted odds ratios (aor), and their respective % confidence intervals ( % ci) of the key associated factors for dental caries in primary school children aged - years (continued) role of cultural habit of using chewing stick (miswak) for cleaning teeth on better outcome observed among children starting brushing at ages - compared to those starting brushing at or years in saudi arabia. given the importance of brushing teeth regularly and mouthwash use in maintaining good oral hygiene and preventing dental caries [ ] , and lower prevalence of these habits observed in our study, detailed investigation of various brushing practices (e.g., use of fluoridated/non fluoridated toothpaste, and use of chewing stick for cleaning teeth), and other oral hygiene practices (e.g., use of fluoride containing mouthwash) among primary school children in saudi arabia is necessary. furthermore, interventions aimed at encouraging good oral health behaviors among children should be undertaken. the negative attitude or apprehension towards visiting a dentist was clearly evident in our study, where only . % ( % ci . - . %) of children visited a dentist for regular check-up, while the others visited for symptomatic treatment (e.g., toothache). the problem was even worse among younger children in saudi arabia; a mere % of children visited dentist for regular checkup on their first visit [ ] . this dangerous trend might have prevented patients from availing sound advice on preventive oral health practices, thereby contributing to high prevalence, delayed recognition, and management of dental caries in saudi arabia. therefore, saudi children would benefit from publicly funded school-based dental screening programs that aid in timely detection and management of dental and other oral health problems. in addition, regular dental screening programs targeted at school children have an added benefit of realizing cost savings due to reduced need for advanced dental care [ ] . the present study found a . (or = . , % ci . - . )-fold higher risk of dental caries among children falling asleep with the bottle in their mouth, which was consistent with literary evidence [ ] [ ] [ ] . however, the magnitude of risk among australian children sleeping with a bottle in mouth was much lower (or = . , % ci = . - . ) [ ] . it was suggested that decreased salivary flow and reduced swallowing reflex as the child gets drowsier would allow carbohydrates to remain in the mouth and pool around the teeth priming the area for bacterial attack [ , ] . the practice of frequently consuming sugary snacks between meals was associated with dental caries in our study. however, current evidence has been inconsistent with some studies indicating a positive association [ , ] , while others failed to observe such a relationship [ ] . therefore, further evaluation and confirmation of this globally relevant predictor is warranted. although breast feeding is commonly practiced in western countries [ , ] , the practice of mixed feeding or partial breast feeding (with breast milk and powdered milk) was predominant in saudi arabia [ , ] . children in our study that were never breast-fed had higher risk of caries, which was consistent with existing literature [ ] [ ] [ ] . breast milk by itself was not cariogenic [ ] , but the reported cariogenicity of certain infant formulas [ ] and a higher risk associated with practice of breast feeding until late infancy (> months -or = . ; % ci . - . ) [ ] should not discourage the practice of mixed feeding until the emergence of new evidence. interestingly, children in our study that were exclusively breast-fed also experienced higher risk of caries, rendering support to the practice of mixed feeding. as noted in previously published literature [ ] , it is possible that the practice of breast feeding until late infancy could have played a role in excess risk observed in saudi children; however, further research based on a larger sample is warranted to confirm our findings and determine the role of duration of exclusive breast feeding on caries risk among children in saudi arabia. furthermore, our study identified that eating patterns and food choices play an important role in dental caries experience in children. interestingly, the observed association between flavored milk and dental caries in this study could be a result of evolving trends in milk consumption practices in saudi arabia. although prior observational studies [ , ] contrast our findings, a moderate cariogenic potential of flavored milk observed in a recent animal experiment and the possibility of developing nations adopting this new trend warrant further evaluation [ ] . incidentally, our study contributed towards ever increasing evidence for the association between dental caries and sodas (or soft drinks) [ ] [ ] [ ] . the acidic content of these soft drinks combined with sugars were known to reduce oral ph and increase the cariogenic potential of tooth [ ] . it is noteworthy that low consumption of fresh fruits (less than twice a week) was associated with increased risk of dental caries among primary school children in this study. in contrast, the literary evidence did not provide a clear benefit of eating fresh fruits in preventing cariogenesis [ , ] . however, certain fruit extracts (e.g., morinda citrifolia) have been associated with inhibiting the growth of cariogenic bacteria [ ] , indicating the need to further evaluate the relevance of fresh fruit consumption to dental caries experience. in general, our findings were consistent with studies that linked intake of foods with high sugar content and dental caries in saudi arabia [ , ] and other places [ ] [ ] [ ] ] . the strengths of this study are multi-fold. information from various risk domains was systematically analyzed to aid in prioritizing the modifiable factors associated with dental caries experience in children. unlike several prior studies in this area [ , , , , ] , this study addressed the issue of multicollinearity and corrected potential bias from small sample in the analysis. the comprehensive nature of information collected encompassing various risk domains enabled us to evaluate the relative importance of individual factors over socioeconomic factors, a component seldom addressed in previous studies. our study provides much needed baseline statistics on several population characteristics to aid not only local authorities, but also international organizations (e.g., who) to evaluate and improve the health programs aimed at mitigating the burden of dental caries in children. however, certain limitations of this study should be considered while interpreting the results. a self-administered questionnaire was used as the main study instrument, which is subjected to recall bias. however, we do not expect our results to be grossly affected by recall, owing to recurrent and current themes tested in the questionnaire. for example, we would expect a more accurate recollection of tooth brushing habits and child feeding practices that were routine activities performed in the recent past; collection of information on flavored milk, a recent trend in saudi arabia, serves as an example for current themes. the study sample was restricted to - -year-old male primary school children in riyadh city of saudi arabia, which warrants caution in generalizing the results to the entire country; however, given the cultural homogeneity and urbanity of the area, we would expect our estimates to be relevant to general population. our study does not support generalizing the results to girl children, as our sample was restricted to boys to comply with school regulations and cultural sensitivities of saudi population. although some of our findings could be relevant to girls owing to shared cultural practices, future research should evaluate and confirm gender-related differences. moreover, the cross-sectional nature of this study warrants against drawing causal inferences. the burden of dental caries is high in saudi arabia with eight out of ten primary school children aged - years suffering from this preventable condition. several individual factors encompassing three risk domains, including oral health behaviors and practices, child feeding practices, and dietary habits, were found to be more relevant factors associated with dental caries than socioeconomic factors. our results were consistent with findings in developed world where poor brushing habits, lack of dental coverage in health insurance, and high consumption of sodas were predominantly associated with dental caries. future research should focus on confirming some of the unique or globally relevant associated factors for dental caries identified in our study, including late adoption of brushing, frequent consumption of sugary snacks between meals, and consumption of fresh fruits and flavored milk. our results support the development and implementation of public awareness campaigns or health education programs targeted at primary school children to promote good oral health behaviors, feeding practices, and dietary habits. additional file : table s . unadjusted odds ratios (uor), adjusted odds rations for variables selected within each risk domain (dor), and adjusted odds ratios (aor) for variables selected from all four risk domains at different steps of model selection process*. (docx kb) abbreviations % ci: % confidence interval; aor: adjusted odds ratio; dmft index: decayed, missing and filled teeth index; fdi: fédération dentaire internationale; mers-cov: middle east respiratory syndrome-corona virus; or: odds ratio; sd: standard deviation; uor: unadjusted odds ratio; who: world health organization years lived with disability (ylds) for sequelae of diseases and injuries - : a systematic analysis for the global burden of disease study a systematic review of population-based dental caries studies among children in saudi arabia the world oral health report : continuous improvement of oral health in the st century--the approach of the who global oral health programme global goals for oral health evaluating dental awareness and periodontal health status in different socioeconomic groups in the population of sundernagar socio-economic inequalities and oral health in canada and the united states access to care, health status, and health disparities in the united states and canada: results of a crossnational population-based survey department of health and human services. oral health in america: a report of the surgeon general caries experience and its relationship with parent's education, occupation and socio economic status of the family among - years old preschool children of sri ganganagar city, india. open journal of dentistry and oral medicine oral hygiene practices, dental knowledge, dietary habits and their relation to caries among male primary school children in al hassa, saudi arabia sugar consumption and dental caries: evidence from countries the consumption of flavored milk among a children population. the influence of beliefs and the association of brands with emotions world health organization. oral health surveys: basic methods. th ed. geneva: world health organization prevalence of dental caries in primary and permanent teeth and its relation with tooth brushing habits among schoolchildren in eastern saudi arabia socioeconomic status and selected behavioral determinants as risk factors for dental caries can socioeconomic status indicators predict caries risk in schoolchildren in saudi arabia? a cross-sectional study. oral health prev dent prevalence of dental caries and associated social risk factors among preschool children in riyadh, saudi arabia risk indicators and risk predictors of dental caries in schoolchildren use of sweet snacks, soft drinks and fruit juices, tooth brushing and first dental visit in high dmft - year olds of riyadh region oral hygiene practices and first dental visit among early childhood caries children in riyadh. pakistan oral & dent jr prevalence of caries in primary school children in saudi arabia caries prevalence in saudi primary school children of riyadh and their teachers' oral health knowledge, attitude and practices caries experience of children aged - years in jeddah, saudi arabia prevalence of dental caries, severity, and pattern in age to -year-old children in a selected community in saudi arabia the relationship between diet and dental caries in and year old children in the emirate of abu dhabi caries experience of -year-old children in alkharj, saudi arabia prevalence and severity of dental caries are associated with the worst socioeconomic conditions: a brazilian cross-sectional study among -year-old males low maternal schooling and severity of dental caries in brazilian preschool children oral health status among -and -year-old jordanian schoolchildren. oral health prev dent dental caries predictors in countries with different human development index: a review of articles fluoride toothpaste and toothbrushing; knowledge, attitudes and behaviour among swedish adolescents and adults factors related to dental health in -year-old children: a cross-sectional study in pupils effect of toothbrushing frequency on incidence and increment of dental caries: a systematic review and metaanalysis caries prediction model in pre-school children in riyadh, saudi arabia early childhood caries in northern philippines world health organization. oral health promotion: an essential element of a health-promoting school: world health organization breastfeeding duration and childhood caries: a cohort study dietary habits and early childhood caries intensity among young children pattern and severity of early childhood caries biological mechanisms of early childhood caries causes, treatment and prevention of early childhood caries: a microbiologic perspective the relationship between snacking habits and dental caries in school children caries risk assessment in an educational environment role of dietary habits and diet in caries occurrence and severity among urban adolescent school children breastfeeding trends in canada infant feeding practices and the decline of breast feeding in saudi arabia breast feeding in a saudi arabian community. profile of parents and influencing factors feeding practices of greek children with and without nursing caries breast feeding, bottle feeding and dental caries in kuwait, a country with low-fluoride levels in the water supply early childhood caries and feeding practices in kindergarten children investigation of the role of human breast milk in caries development cariogenicity of different types of milk: an experimental study using animal model breastfeeding and the risk of dental caries: a systematic review and meta-analysis influence of cocoa and sugar in milk on dental caries incidence milk, flavoured milk products and caries evaluating the cariogenic potential of flavored milk: an experimental study using rat model medically administered antibiotics, dietary habits, fluoride intake and dental caries experience in the primary dentition dental caries and beverage consumption in young children carbonated soft drinks and dental caries in the primary dentition dental erosion and severe tooth decay related to soft drinks: a case report and literature review dietary pattern of finnish children with low high caries experience diet, nutrition and the prevention of dental diseases role of aqueous extract of morinda citrifolia (indian noni) ripe fruits in inhibiting dental caries-causing streptococcus mutans and streptococcus mitis dental caries, sugar consumption and restorative dental care in - -year-old children in riyadh, saudi arabia oral health knowledge, attitudes and behaviour of children and adolescents in china we would like to thank the administration of the schools, parents, children, and dental professionals who participated and provided assistance in our study. we also thank king abdullah international medical research center (kaimrc) for partially funding our research. king abdullah international medical research center (kaimrc) partially funded our research (grant number sp / ). the funders had no role in the study design; collection, analysis, and interpretation of data; decision to publish; and preparation of the manuscript. please contact the author for data requests.authors' contributions ya and hj conceived the project idea. ya, aa, ny, and hj designed the study and approved the methodology. ya, aa, and hj participated in the data collection. ya, ny, and hj managed the study data and conducted the formal data analysis. all authors contributed extensively towards the preparation of this manuscript and approved the version submitted to the journal. all authors read and approved the final manuscript.ethics approval and consent to participate ethics approval for this study, including oral examination of the children, was provided by the institutional review board (irb) at king abdullah international medical research center (kaimrc) in riyadh under protocol number sp / . informed consent was obtained from the parents. 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. 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- - x gr authors: aldarhami, abdu; bazaid, abdulrahman s; althomali, omar w; binsaleh, naif k title: public perceptions and commitment to social distancing “staying-at-home” during covid- pandemic: a national survey in saudi arabia date: - - journal: int j gen med doi: . /ijgm.s sha: doc_id: cord_uid: x gr objective: social distancing measures, such as stay-at-home, are currently implemented to control the covid- pandemic in many countries, including saudi arabia. the aim of this study was, therefore, to evaluate the awareness and adherence of the saudi population to these measures. methods: a web-based questionnaire was designed with questions (eight questions related to demographics, three related to the awareness of social distancing (stay-at-home) and five related to the overall practice of social distancing). results: a total of participants completed the survey [ . % females, . % young individuals (aged – years), . % bachelor degree holders and . % from the western region]. the saudi ministry of health (moh) was the main source of information about covid- for most of the participants ( . %). high awareness ( . %) regarding stay-at-home was observed, associated mainly with female participants, those from the middle region and those with a high education and income. the overall implementation of social distancing was satisfactory (score . / ), with . % never leaving home during the stay-at-home period. better adherence to social distancing was observed among female participants, higher degree holders and those aged over years. conclusion: organised plans by the saudi moh have been effective in raising awareness and improving the practice of social distancing among public. however, the observed lower practice of social distancing by individuals with a lower education and income indicates the need for targeted interventions to achieve better outcomes. in late december , a novel strain of coronavirus emerged, which was first reported as a national outbreak in wuhan, china. , subsequently, this disease was designated as coronavirus disease (covid- ) , which is caused by the severe acute respiratory syndrome, coronavirus (sars-cov- ). the wide spread of the disease since then led the who to announce covid- as a pandemic on march th, . to date (june th, ), sars-cov- has caused over nine million cases and , deaths globally. in addition to its lack of effective vaccines or treatments, sars-cov- has high infectivity even before the onset of symptoms, which can take up to days to manifest, , during which time transmission is possible. , , consequently, this pandemic has been announced as a high concern for health, with containing its spread worldwide proving an extremely challenging task. , currently, health authorities are left with only preventive measures to tackle the spread of the pandemic. , a few measures, such as social distance, self-isolation, home-isolation and self-quarantine, have been introduced as feasible precautionary steps that can be implemented to limit, delay or flatten the reproduction rate (r ) of sars-cov- . , these terms have showed up more frequently in the media and various scientific publications. [ ] [ ] [ ] the exact definition of such terms overlap as they generally share similar meanings, which can emphasise the physical separation or distance between healthy people and individuals with confirmed or suspected infection. , , social distancing measures were used in the past to combat the spread of other viral and bacterial contagions, including the plague and severe acute respiratory syndrome (sars). implementing these measures and precautions in the current sars-cov- pandemic has proven effective in controlling or containing this infection in china and other far eastern countries. even before the first confirmed case of covid- in the kingdom of saudi arabia (ksa), the national authority closed shopping centres and suspended flights, face-to-face education and physical attendance at most governmental agencies as preventive steps. further precautions followed, entailing suspending prayers at mosques and implementing a lockdown in cities with high numbers of cases. , this aimed to limit the population's mobility and minimise social gatherings in order to control transmission. nevertheless, to date (june th, ), the statistics have reported over , cases and deaths in ksa and the numbers are continuing to rise. therefore, in order to confirm whether preventive steps have been successfully implemented in ksa, the overall understanding and adherence of the general public to physical separation should be evaluated. likewise, it is crucial to ensure that the public can access information about preventive measures from trusted agencies. hence, the aim of the current study was to evaluate the awareness and practices of the saudi population in relation to social distancing (stay-at-home). a cross-sectional, observational study was conducted to evaluate the overall awareness and adherence of the saudi population to social distancing to control the spread of covid- . the survey tool was written in arabic, the mother tongue of the target population, and was built using an online survey form. to ensure a wide distribution, the dissemination to the target participants was carried out using various social media (twitter, whatsapp and snapchat) between march th and april th, . the questionnaire included introductory information to inform the participants about the purpose of the study and consent information to ensure that participation in the study was voluntary, while ensuring the confidentiality of personal data. participants under years were excluded from this study. the questionnaire was created according to novel coronavirus ( -ncov) infection guidelines. to ensure the accuracy of the collected information, multiple choice and close-ended questions were used in this study. used language for this questionnaire was validated by five multidisciplinary experts to suit the target participants. the resulting pre-final survey was piloted with individuals from the general population of different ages and genders to address any ambiguity in the questions and assess the extent to which these questions are related to the objectives of this study. the questionnaire was then edited based on the collected feedback, which was used to prepare a final version for the study. the final questionnaire contained questions, divided into three sections. the first covered the demographics of the participants (age, gender, monthly income, education level, marital status, occupation and geographical region of residence). the second covered their main sources of information about covid- (the moh, the who, friends and relatives or social media), their understanding of who should stay-at-home during the pandemic (the elderly, children, symptomatic people or the whole population), as well as their beliefs about the possibility of asymptomatic transmission. the final section comprised five questions (supplement ) about the practices of the participants in relation to social distancing. this included questions about their reasons for going out (work, buying necessities, purchasing a meal or entertainment), the amount of time spent outside the home (the number of days per week and hours per day), and their practices when leaving home (whether they leave alone or with others). the responses provided by the participants to each question were given designated scores; one point [ ] for the most appropriate answer and no points [ ] for the least appropriate or uncertain (i do not know) responses (supplement ). the collected responses to the questions intended to measure adherence to the stay-at-home strategy were scored as a quarter [ . ], half [ . ] or one [ ] point for responses of two hours spent outside, less than one hour outside or never leaving the home, respectively. all of the statistical analyses were performed using spss software version . (ibm corp, armonk, ny). the numbers of participants, their percentages, the mean, standard deviation (sd) and the median in relation to the variables describing their knowledge and practices were assessed using descriptive analysis. the overall scores related to their practices were analysed based on their demographic characteristics using a one-way analysis of variance (anova) and independent sample t-test for normally distributed data, while kruskal-wallis and mann-whitney tests were used for the non-parametric analysis. questions testing knowledge were analysed using the chi-square or fisher's exact test to determine whether there were significant differences between the responses in relation to the participants' demographic characteristics. multivariable linear regression was used to identify the factors associated with the overall scores for the participants' practices, which were determined using the stepwise method. to quantify the relationship between the variables, the odds ratios (ors), unstandardized regression coefficients and % confidence intervals (cis) were calculated. a two-steps analysis was conducted to avoid any multicollinearity between the independent variables; first, we checked that the correlation coefficients between the independent variables were below . and, second, that the tolerance and variance inflation factor (vif) values were higher than . and , respectively. statistical significance was defined by a p-value below . . the maximum score assigned to individuals with perfect adherence to the stay-at-home strategy was . to ensure the reliability and reproducibility of the questionnaire, the cronbach's alpha was conducted, which scored . , indicating a very good level of internal consistency between the questions. a total of , participants completed the survey, of whom . % were female, and most were young individuals ( . % and . % from the - and - years age groups, respectively) and married ( . %). in addition, the contributors to this survey were mainly bachelor degree holders ( . %), employees ( . %), with low income ( . %), living in western saudi arabia ( %) and residents of cities ( . %) (supplement ). the participants were asked about their sources of information about covid- to determine the most widely used sources by the saudi population. about % and % of the participants selected the saudi moh and social medial as their main sources of knowledge, respectively. seeking information about covid- from friends, colleagues or relatives was the least favoured source used by the saudi participants ( table ) . the participants expressed their views about social distancing. the majority ( . %) were of the view that "everyone" should observe social distancing as a preventive measure, and most expressed a belief that asymptomatic transmission was possible ( . %). this translates into an . % awareness, based on both items taken together ( table ). the multiple logistic regression analysis (table ) showed that females (or . , p < . ) and participants from the middle region (or . , p = . ) were considerably more likely to choose the appropriate response to the question about social distancing. in contrast, participants from the - years age group (or . , p = . ) and those with a secondary education or below (or . , p < . ) were less likely to choose the appropriate response to the question. likewise, participants with higher educational levels (master or phd; or . , p < . ) and those with high income (> , sr; or . , p = . ) were more aware of the likelihood of the risk of the asymptomatic transmission of covid- (table ). in contrast, a lack of awareness about asymptomatic transmission was found to be associated with participants from the southern part of the kingdom (or . , p = . ), those with a secondary and below educational level (or . , p < . ), diploma holders (or . , p = . ) and those with a low income (< sr) (or . , p < . ) ( table ) . the practice of the participants was scored based on supplement ; a summary of the scores in relation to demographics is shown in table and the results of the regression analysis are shown in table . the average score of the respondents was approximately . (sd . , range - ), representing a . % implementation. however, just over a third ( . %) of the participants confirmed that they had never left home since social distancing was introduced ( table ). females (β . , p < . ), master or phd holders (β . , p = . ), people from the - years age group (β . , p = . ) and individuals over years (β . , p < . ) were associated with a higher score (table ). in contrast, participants with a low income (- - sr, β − . , p = . ), employees (β − . , p < . ), entrepreneurs (β − . , p = . ), retired participants (β − . , p = . ) and residents in the south (β − . , p = . ) or north (β − . , p < . ) of the kingdom were associated with a lower score (table ). almost half ( . %) of the participants went out to buy necessities, whereas going to work or a hospital was the reason for leaving home for almost % of the respondents. in addition, nearly a third ( %) and about a quarter ( %) of the participants stated that they spent one day per week and less than an hour per day outside, respectively. approximately one in five of the respondents acknowledged that they left their home - days a week for a total time of - hours per day. in the context of practicing social distancing, about % of the participants went out alone, while % were accompanied by another adult (table ). awareness of the public is crucial in controlling the spread of covid- , both nationally and internationally, because the level of awareness in society affects the implementation of precautionary measures. therefore, this study was conducted to analyse the knowledge and practices of the population in ksa in relation to staying at home as a preventive measure for containing the covid- pandemic. to the best of our knowledge, this is the first study performed to evaluate the adherence of individuals to the stay-at-home measure in ksa and to provide suggestions about the multiple reasons behind any deficiency in its application. a survey was distributed and , responses were returned by participants from different demographic groups to ensured that the collected data represent, to an acceptable level, the saudi population. the responses indicated a high level of awareness among the saudi population, with the majority of the participants ( %) expressing the view that everyone should practice social distancing. the respondents ( %) were also aware of the potential asymptomatic transmission of the infection. a population with this level of awareness is speculated to practice social distancing successfully. previous studies conducted on chinese and japanese populations , produced similar findings regarding the public's knowledge about covid- . in the context of raising awareness, the local public health has established multiple campaigns and launched health applications and call centres, offering the public information about covid- as well as providing answers to related queries. this approach has provided saudi individuals with information related to the benefits of staying at home and encouraged its implementation. the respondents indicated that the saudi moh was their , consequently, the saudi authorities acted very early (even before the pandemic reached ksa) by establishing campaigns to enhance public awareness and engage the public in actively learning and searching for information about covid- and the related precautionary measures. in contrast, a recent study conducted in the initial stage of this pandemic demonstrated that the participants living in three arabic-speaking countries, including saudi arabia, had a moderate level of knowledge ( %). this could be because more than a quarter of the participants were over years-old. during the covid- pandemic, the information to raise the awareness of individuals was mainly delivered online, which may not be accessible or easy to use by the elderly. in contrast, since the majority of the participants in this study were found to be young, it can be speculated that the observed high level of knowledge of the participants is linked to their ability to access online information about covid- more easily. therefore, since elderly people are more susceptible to covid- than younger individuals, national public health needs to ensure that the information about this pandemic is received by all age groups. the local health authority recently introduced the approach of texting individuals with information about covid- in multiple languages. this step will increase the knowledge of people of various age groups, who speak various languages, as well as the residents of the rural areas, where the internet connection can be poor. in line with the findings of, , the level of education was positively associated with increased awareness. this is self-evident, as well-educated individuals are able to seek, access and understand information far more easily than those who are less well educated. regional discrepancies were demonstrated in relation to the awareness within saudi society about social distancing, with participants living in the middle of the kingdom showing higher levels of knowledge compared to the other regions. although the total number of recorded covid- cases is almost identical between the cities in the western region, eg, makkah ( ) and medina ( ), and the therefore, the higher awareness of individuals in the middle region of saudi arabia may have contributed to the decrease in the numbers of daily cases in riyadh. with respect to the practice of staying at home, the overall implementation of social distancing by the participants was found to be moderate ( . / ). however, a high level of implementation ( / ) was followed by % of the participants, who never left home after the introduction of the stay-at-home advice. in addition, the participants who left home mentioned the reasons for this, such as buying necessities ( %), going to work ( %) or going out for leisure (around %). furthermore, the majority of those who left home ( % of the respondents) returned within two hours, and their frequency of leaving was less than three days a week, showing a satisfactory level of implementation of social distancing. moreover, the majority of responders either went out alone ( %) or with another adult ( %), indicating a positive adherence by limiting contact between individuals to reduce viral dissemination among the population. these results are supported by a mobility report for the saudi communities during the covid- pandemic, which was provided by google, in which about a % reduction was observed in the number of people visiting food warehouses and pharmacies in the kingdom. these outcomes should increase the overall stay-at-home practice from a moderate to a high level; however, there still remains a possibility for greater improvement, encouragement and support to reach higher levels of adherence, especially for those who left home seeking entertainment. as a good adherence to social distancing by chinese individuals was a key element in the efforts by the authorities to contain the covid- pandemic, covid- may be contained in saudi arabia relatively early. nevertheless, the behavioural changes of the saudi population related to the implementation of precautionary measures (eg, washing hands) outside the home need to be investigated. a statistical analysis of the responses revealed that females, people aged years or over and master or phd holders showed a higher commitment to social distancing compared to their counterparts. this is in agreement with a previous study on the awareness of saudi people regarding mers, which demonstrated that females were more likely to apply safety precautions than males. a possible explanation for this might be that, culturally, males tend to go out more frequently than females. in relation to the better adherence by people of middle age and older, the people of this age group may have been influenced by published findings from chinese epidemiological studies, which showed that older patients are more prone to develop invasive forms of covid- , with a high fatality rate. in addition, the study showed a reduced practice of staying at home among employees and entrepreneurs, possibility because the nature of their work requires them to leave their home regularly compared to other types of jobs. notably, residents of the northern and southern parts of ksa presented a lower engagement with social distancing, which could be attributed to the delayed appearance of covid- cases in those regions. areas with limited cases of covid- tend to be associated with reduced knowledge and practice. the immediate application of the lockdown strategy has proven effective in flattening the curve of covid- 's spread in the cities (regions) of the kingdom, as the northern and southern parts were protected from a sharp propagation of cases. , a full curfew ( hours a day) was applied to cities with the high numbers of daily cases in the western, eastern and middle regions, whereas the less affected cities in northern and southern regions were locked down partially ( - hours a day). this might explain the variation in the level of overall adherence between the regions. however, it was found that the application of the lockdown strategy managed to limit their frequency of leaving home for about % of the participants. the establishment of the national lockdown strategy may have been treated by individuals as an alarming sign, indicating the serious, urgent need for action, which may have encouraged them to practice better adherence. in line with, the responses by low-income individuals reflected a lower social distancing practice, and this finding might be related to their need to work to secure their income. fortunately, a minority of the respondents admitted a lack of commitment to social distancing, mainly because of the absence of cases in their area. poor practice can result from the lower knowledge of individuals about asymptomatic carriers who can spread the infection. these groups who lack good practice regarding social distancing, especially those with a low income, need to be investigated more closely, so that appropriate solutions to enhance their adherence can be implemented. all data generated during this study are included in this published article and its supplementary file. this study was approved by ethics committee at the university of hail (ethics approval reference number h- - ). all authors made substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; took part in drafting the article or revising it critically for important intellectual content; agreed on the journal to which the article will be submitted; gave final approval of the version to be published; and agree to be accountable for all aspects of the work. this study was funded by scientific research deanship at university of ha'il, saudi arabia through project reference number: covid- . the authors declare that there is no conflict of interest. assessment of iranian nurses' knowledge and anxiety toward covid- during the current outbreak in iran review of coronavirus disease- (covid- ) naming the coronavirus disease (covid- ) and the virus that causes it who declares covid- a pandemic world health organization. who covid- dashboard preparedness and response to covid- in saudi arabia: building on mers experience covid- and importance of social distancing langade dcovid- . awareness among healthcare students and professionals in mumbai metropolitan region: a questionnaire-based survey social distancing during the covid- pandemic: staying home save lives covid- ) the covid- pandemic calls for spatial distancing and social closeness: not for social distancing! how long should social distancing last? predicting time to moderation, control, and containment of covid- knowledge, attitudes, and practices towards covid- among chinese residents during the rapid rise period of the covid- outbreak: a quick online cross-sectional survey center for disease control and prevention. history of quarantine covid- social distancing in the kingdom of saudi arabia: bold measures in the face of political, economic, social and religious challenges covid dashboard: saudi arabia the saudi center for disease prevention and control. novel coronavirus ( -ncov) infection guidelines adoption of personal protective measures by ordinary citizens during the covid- outbreak in japan attitude and practice (kap) study about middle east respiratory syndrome coronavirus (mers-cov) among population in saudi arabia knowledge and practices towards covid- during its outbreak: a multinational cross-sectional study characteristics of and important lessons from the coronavirus disease (covid- ) outbreak in china: summary of a report of cases from the chinese center for disease control and prevention changes in contact patterns shape the dynamics of the covid- outbreak in china covid- community mobility report saudi arabia the international journal of general medicine is an international, peer-reviewed open-access journal that focuses on general and internal medicine, pathogenesis, epidemiology, diagnosis, monitoring and treatment protocols. the journal is characterized by the rapid reporting of reviews, original research and clinical studies across all disease areas. the manuscript management system is completely online and includes a very quick and fair peer-review system, which is all easy to use. visit http://www.dovepress.com/ testimonials.php to read real quotes from published authors. key: cord- - iqtj db authors: elachola, habida; memish, ziad a title: oil prices, climate change—health challenges in saudi arabia date: - - journal: lancet doi: . /s - ( ) - sha: doc_id: cord_uid: iqtj db nan foods, such as sugar-sweetened beverages and energydense, nutrient-poor foods, in the school environment; informed nutrition education as part of the core curriculum; and ensuring levels of physical activity for all children according to who recommendations. in addition to the new approaches, the imperative to implement existing standards has been underlined. echo noted the disappointing lack of progress on implementation of who's set of recommendations on the marketing of foods and non-alcoholic beverages to children. it reiterates the need to implement regulatory measures, such as the international code of marketing of breast-milk substitutes, and to develop regulations on the marketing of complementary foods and beverages for infants and young children. echo's recommendations call for various stakeholders to take action, such as who to institutionalise a crosscutting and life-course approach to ending childhood obesity and for civil society, philanthropic and academic institutions, and the private sector to mobilise their comparative advantage to end childhood obesity (panel ). these actions notwithstanding, echo remains fi rmly of the opinion that it is the primary responsibility of governments to ensure that policies and actions address the obesogenic environment and to provide guidance and support for optimum development at each stage of the life-course. by improving and integrating these actions, there will be major benefi ts to other parts of the maternal, reproductive, child health, and non-communicable disease prevention and control and health systems agendas. first, along with the rising oil revenues in recent decades, saudi arabia has seen a rapid epidemiological transition in the population (table). the uptake of some health-promoting behaviours has been limited by saudia arabia's unemployment rate ( · % in ), moderate levels of education, and climatic and sociocultural conditions. , , the high burden of undiagnosed and uncontrolled diabetes and hypertension, , will consume a large proportion of the health budget. second, future temperature in the region is projected to increase consistently and exceed the threshold deemed unsuitable for human adaptability. this changing climate will have an eff ect on the promotion of some healthy lifestyle habits, the country's production of fresh fruits and vegetables, and micronutrient defi ciencies. for example, vitamin d defi ciency from inadequate exposure to sun and limited intake of enriched products is common in saudi arabia. finally, there is a need for sustained investment in the control of emerging infectious diseases in the region. such control eff orts are important given the risk of emerging diseases within saudi arabia, such as middle east respiratory syndrome, and as a result of disease importation through the large expatriate workforce and the - million pilgrims for hajj and - million pilgrims for umrah who come to saudi arabia each year from more than countries. , although economic recession is often feared as a "health tragedy", evidence from high-income countries is mixed and related to variations in social and political contexts. , in high-income countries, some health indices showed counter-cyclical eff ects with economic contractions (eg, increases in suicides, depression, and anxiety disorders and worsening reproductive health outcomes). , however, mortality is shown to be pro-cyclical and it decreases during rapid economic contractions. in high-income countries, there are generally slower declines in mortality during periods of economic growth and greater declines in mortality during recessions. in low-income countries, economic growth seems to improve health through improvements in basic services, until a country reaches $ - gdp per person. declines in mortality in high-income countries during recession could be related to decline in excess mortality from modifi able causes of death, such as those arising from alcohol abuse and motor vehicle accidents. , given that saudi arabia has one of the highest rates of traffi c-related deaths globally, the country might benefi t from the austerity measures in this regard. if saudi arabia maintains increased relief spending on child health, improvements in access to nutrition and health, and strong infectious diseases control then these approaches can also help reduce mortality. since saudi arabia's sociodemographic and geopolitical foundation is diff erent from that of the case studies available thus far, it is diffi cult to predict potential health eff ects of the present economic recession and newly proposed health-sector reforms. saudi nationals (and pilgrims coming to mecca for the hajj) are entitled to free health care and the government accounted for % of health care spending in (about % of gdp). the expatriate workforce of saudi arabia, which accounts for % of the total population and about % of the private sector workforce, are not covered by the government health-care system. , the proposed nationalisation process to reduce the expatriate workforce by employing more saudi nationals in the employment sector could adversely aff ect the health-care workforce since about % of physicians and % of nursing staff in saudi arabia are expatriates. a much needed boost in the country's health promotion portfolio would require expertise in various public health disciplines that are currently in short supply in saudi arabia. the greatest burden of economic recession generally falls on the unemployed. , about a third of the million population of saudi arabia are younger than years, and the child dependency ratio is % (ratio of people below working age to workforce). in , the rate of unemployment in saudi arabian nationals was · % for people aged - years (men · %, women · %). , a recent emphasis on privatisation of health and preventive care, or even cost sharing of preventive care, could lead to an increase in overall health-care costs if people forego essential medications, immunisations, or routine clinic visits such as antenatal care. high body-mass index dietary risks raised fasting plasma glucose high blood pressure we do not know how long the current economic downturn will last in saudi arabia. anticipating potential eff ects of recession at an early stage of the crisis can inform health-sector reforms to diminish or avoid its harmful consequences on nation's health. despite saudi arabia's unique challenges, the ministry of health has so far been successful in providing state-of-the-art medical services to its citizens. for example, saudi arabia's premarital sickle cell screening is a unique initiative. despite free health care, saudi arabia's shortcomings are in the control of non-communicable diseases and mitigation of risk factors for disease. only % of saudi adults have had a preventive care visit. , there is a need to consider multipronged approaches to health promotion and avoidance of risk factors, including those that fall outside the services of health ministry (eg, enforcement of motor vehicle accident prevention advisories, point of sale restrictions on tobacco). by training primary care providers to serve as advocates for health promotion, each encounter between the provider and patient can be used as an opportunity to educate patients about a set of prevention messages. informed personal decision making is important to increase the uptake of healthy lifestyles and prevention recommendations; this is a process achieved through education and a sense of personal empowerment that comes with employment. outreach to civic organisations for partnerships in health promotion initiatives can help increase visibility and uptake. beyond the immediate eff ects of the current economic crisis, saudi arabia needs to target its policies to mitigate the eff ects of climate change. agricultural approaches such as hydroponics, vertical farming, and landscaping with food-producing plants can increase food production, enable healthy eating habits, and improve air quality. additionally, enrichment of food products (vitamin d, folic acid, iodine) is an easy and cheaper alternative to promotion of supplement use by individuals. the transition in the country's health-care delivery to the private sector and cost-sharing should be implemented without compromising services for the unemployed and uninsured. similarly, eff orts to nationalise the health labour force should consider continuity in essential service delivery. saudi arabia's religious leadership can encourage the population to adhere to guidance on health promotion, which is particularly important for mental health where health-care infrastructure is not adequate. health security cannot be achieved by focused eff orts from the health ministry alone; nations that off er greater social safety nets are better positioned to diminish the health eff ects of economic recession. finally, implementation of evidence from case studies on the health eff ects of the economic crisis are useful and can contribute to the emerging body of literature on economics and health. health-care reform was long overdue in saudi arabia and the current crisis aff ords the country an opportunity to do it right. saudi arabia's future health security will rely on the choices made today by its health policy makers. ministry of health, riyadh, saudi arabia (zam); college of medicine, alfaisal university, riyadh , saudi arabia (zam); and atlanta, georgia, usa (he) zmemish@yahoo.com we declare no competing interests. saudi arabia's economic time bomb. the brookings institution riyadh plans radical surgery to rejuvenate saudi health sector demography, migration and labour market in saudi arabia burden of disease, injuries, and risk factors in the kingdom of saudi arabia kingdom of saudi arabia status of the diabetes epidemic in the kingdom of saudi arabia hypertension and its associated risk factors in the kingdom of saudi arabia, : a national survey cost of diabetes in the kingdom of saudi arabia future temperature in southwest asia projected to exceed a threshold for human adaptability defi ciencies under plenty of sun: vitamin d status among adults in the kingdom of saudi arabia hajj: infectious disease surveillance and control years of austerity takes its toll on greek health care the eff ect of economic recession on population health six-year outcome of the national premarital screening and genetic counseling program for sickle cell disease and β-thalassemia in saudi arabia breast cancer screening in saudi arabia: free but almost no takers low uptake of periodic health examinations in the kingdom of saudi arabia key: cord- - ub j x authors: bleibtreu, a.; bertine, m.; bertin, c.; houhou-fidouh, n.; visseaux, b. title: focus on middle east respiratory syndrome coronavirus (mers-cov) date: - - journal: med mal infect doi: . /j.medmal. . . sha: doc_id: cord_uid: ub j x since the first case of human infection by the middle east respiratory syndrome coronavirus (mers-cov) in saudi arabia in june , more than cases of confirmed mers-cov infection and related deaths have been reported since the th of october . the vast majority of these cases ( %) were reported in saudi arabia but the epidemic has now spread to countries and has not ceased years later, unlike sars-cov that disappeared a little less than years after emerging. due to the high fatality rate observed in mers-cov infected patients ( %), much effort has been put into understanding the origin and pathophysiology of this novel coronavirus to prevent it from becoming endemic in humans. this review focuses in particular on the origin, epidemiology and clinical manifestations of mers-cov, as well as the diagnosis and treatment of infected patients. the experience gained over recent years on how to manage the different risks related to this kind of epidemic will be key to being prepared for future outbreaks of communicable disease. the first case of infection attributed to middle east respiratory syndrome coronavirus (mers-cov) was detected in saudi arabia in june [ ] . mers-cov then spread to several neighboring countries, mainly jordan and qatar (see fig. ), and imported cases of the disease were reported throughout the world in asia, africa, europe and the americas [ ] . by the th of october , con- the first two coronaviruses demonstrated to cause respiratory infections in humans, the coronaviruses e and oc , were identified in the s. they were held responsible for respiratory infections of moderate severity in humans. despite these viruses being identified in several reports as causing lower respiratory tract infections, it was generally accepted that coronaviruses were of low pathogenicity until the emergence of sars-cov (severe acute respiratory syndrome coronavirus) in , a virus with a fatality rate estimated at %. the sars outbreak that resulted in more than cases was finally contained two years later, in , and the virus has not been detected again since [ ] . there was renewed interest in coronavirus research following the sars epidemic, and two novel endemic human coronaviruses were identified, nl and hku respectively in and , but could not be replicated in cell culture. both of these new viruses were responsible for respira-tory infections of moderate seriousness like the coronaviruses e and oc . great effort has been made to identify coronaviruses in animal populations, both before and after the sars outbreak, in order to better understand and control the risk of animal-to-human transmission. this resulted in the discovery of coronaviruses in numerous animal species, with a few exceptions such as sheep and goats, fish and non-human primates [ ] . the first case of mers-cov infection was reported in jeddah, saudi arabia, in june [ ] . the patient, a -year-old man, died from lung and kidney failure days after being admitted to hospital. very shortly afterwards, in september , a second patient was admitted to hospital in the united kingdom for severe respiratory infection related to a novel coronavirus following travel to the middle east. the new virus was found to replicate in a tissue culture model and was rapidly isolated and identified for both cases [ , ] . retrospectively, other cases of the disease were found to have occurred before the aforementioned cases: in april , an outbreak at zarqa hospital in jordan affected the staff of the intensive care unit, with two fatal cases. the respiratory samples collected were later confirmed to be positive for mers-cov [ ] . these initial cases were rapidly followed by a series of outbreaks in all saudi arabian provinces that were characterized by the infection of health professionals in direct contact with the patients. other similar outbreaks were observed in several neighboring countries: qatar, bahrain, kuwait, jordan and tunisia. health authorities reacted quickly to the reports of these epidemics and the strong resemblance with observed clinical features of sars-cov infections. indeed, although a few patients developed mild infections, the fatality rate for patients infected with mers-cov was over % [ ] . following the identification of mers-cov, great effort was put into finding which animal species it originated from in order to stop the further spread of the disease to humans. mers-cov was very rapidly determined to be genotypically closely related to the betacoronavirus lineage c viruses identified in bats [ ] . based on these findings, and the major role of bats in the genetic diversity and spread of coronaviruses, much of the initial work aiming at finding the natural reservoir of mers-cov focused on bats. however, no conclusive evidence demonstrating that bats were the natural reservoir of mers-cov in the arabian peninsula were found, despite the identification of closely related viruses in bats in sub-saharan africa [ ] , far from the existing outbreaks. very strong epidemiological links were identified between the human cases and camels and resulted in the isolation in camels of viruses that were directly related to mers-cov and that could replicate in cultured human cells [ ] . the investigation of dromedary camel serum collections, some of which collected as early as , demonstrated that the virus was already widespread (seropositivity rate > %) in the east african countries (somalia, sudan and egypt). these countries export dromedary camels to arabian countries, but also in kenya, nigeria, tunisia, ethiopia, burkina faso and morocco [ ] [ ] [ ] . phylogenetic analysis revealed distinct coronavirus lineages in dromedary camels, including one recombinant lineage that led to the mers-cov epidemic in humans [ ] . mers-cov is a betacoronavirus belonging to lineage c. it is an enveloped virus with a positive-sense single-stranded rna genome of about kb. under electron microscopy, virions are generally spherical with surface projections (spikes) formed by the surface protein s creating an image reminiscent of a crown or solar corona. the positive-sense single-stranded rna genome acts as messenger rna (mrna) with a cap and a polyadenylated tail. it plays three roles during the host cell cycle: (i) it acts as the initial rna molecule for the infection cycle; (ii) it is the template for replication and transcription; (iii) it is the substrate that is packaged into the newly assembled viral particles [ ] . the mers-cov genome is organized in the same way as other coronavirus species. the first two thirds of the mers-cov genome contain two overlapping reading frames (orf a and orf b) that translate into the replication-transcription complex including non-structural proteins. the remaining third of the genome encodes the four structural proteins, the spike (s), envelop (e), membrane (m) and nucleocapsid (n) proteins, as well as five accessory proteins (orf , orf a, orf b, orf and orf b) that are not required for genome replication but are probably involved in virulence. the flanking sequences, on both ends of the genome, contain untranslated and regions (utr) (fig. ) [ ] . the viral particle can enter the cell in two ways, which probably contribute to the broad tissue tropism of this virus that replicates mainly in respiratory epithelial cells but can also infect many other cell types. via the endosomal pathway, the s domain of the mers-cov spike protein (s) binds its receptor, dipeptidyl peptidase (dpp ) [ ] , induces endocytosis of the viral particle and a change in the conformation of the s subunit of the s protein that then mediates virus-host membrane fusion and uncoating of virus rna. mers-cov can also enter host cells via a non-endosomal mechanism by direct fusion of the virus with the plasma membrane following s protein cleavage by human proteases [ ] . following entry into the cytoplasm and uncoating of the virus nucleocapsid, the viral genomic rna is translated to produce two polypeptides, pp a and pp b, that form the replicase-transcriptase complex. this initial replicase-transcriptase complex uses the genomic rna to produce non-structural proteins that assemble into the replication complex. the replication complex then replicates the genomic rna and produces other subgenomic rnas that ensure the translation of the structural proteins. virions are assembled at the endoplasmic reticulum membrane as viral proteins and genomic rna are grouped together and then bud into the lumen of the endoplasmic reticulum. the virions are then exported via the secretory pathway of the endoplasmic reticulum into the golgi intermediate compartment and then into the extracellular environment. the m protein drives the packaging process by selecting and organizing the viral envelop components at the assembly sites and interacting with the nucleocapsid to allow budding [ ] . several large serology studies suggest that cases of asymptomatic or mild mers-cov infection occur regularly, although infrequently. the importance of such cases is difficult to assess [ ] . it is therefore difficult to determine whether these cases are due to or take part in human-to-human transmission. several studies suggest that less than % of infected patients transmit the virus to individuals they come into contact with, even at the beginning of an outbreak [ ] . the disease therefore seems to spread due to frequent animal-to-human transmission, from camels to humans, with limited subsequent human-to-human transmissions [ ] . there are unfortunately exceptions to this observation and local outbreaks caused by human-to-human transmission have been observed on a regular basis, mostly in hospitals. to date, the most poignant example is the outbreak that occurred in south korea in which the index case caused secondary cases, among whom were care providers, leading to fatalities [ ] . this outbreak was characterized by the key role of a few "super spreaders", delayed diagnosis, high doctor shopping behavior and the importance of confined spaces (waiting room, hospital room, ambulance). in this example, the resemblance with sars-cov's spreading mechanisms is striking, despite lower degrees of transmission to care providers for mers-cov [ ] . these regular cases of imported-mers, the most recent was reported in england in august [ ] , represent a real threat of local epidemics outside saudi arabia and special screening and isolation procedures need to be implemented in units likely to receive patients suspected of mers-cov infections. when possible, the first measure to be taken is to delay departure, in particular for individuals over or with chronic disease, and for pregnant women or children. such measures are nevertheless challenging to maintain today as that the virus is still present years after its apparition. all other preventive measures aim at preventing both animalto-human transmission and human-to-human transmission. it is therefore recommended to avoid any contact with domestic animals (firstly dromedary camels), their secretions, raw milk and insufficiently cooked meat. it is also advised to avoid eating fruit and vegetables that might have been in contact with animal secretions if not washed and peeled by oneself. to avoid human-to-human transmission, the usual recommendations for preventing the spread of any respiratory virus should be applied: hand washing with soapy water or an alcohol-based solution, covering one's nose and mouth when sneezing, refraining from shaking hands and touching one's mouth and nose with one's hands, avoiding contact with people with respiratory symptoms. finally, a last series of recommendations focus on how to behave in case of suspicious symptoms: (i) consult a doctor as soon as symptoms occur during travel and delay the return until symptoms disappear; (ii) if symptoms occur with days of returning home, consult a doctor and tell him/her about the recent travel [ ] . pcr-based detection methods are currently the preferred option for detecting the virus in respiratory samples and making a diagnosis of mers-cov infection. serology tests can also be performed and are often used for second-line diagnostic investigation in patients with a high suspicion of mers-cov but negative results by direct pcr testing. various respiratory matrices can be used: nasopharyngeal swabs, nasopharyngeal or tracheal aspirates, bronchoalveolar lavage (bal), and even in some cases, induced sputum. the deepest samples, tracheal aspirates and bals, show the greatest sensitivity and significantly higher viral loads [ ] . the genome amplification and detection methods used (pcr) were initially mostly developed in situ and performed in biosafety level (bsl- ) reference facilities. the time to results is generally relatively long, - h, due to the usual time required for conventional pcr testing to which must be added the additional preparation and sample neutralization time needed to protect the laboratory staff against this virus. the pcr methods used are generally semi-quantitative and some studies suggest a correlation between the amount of virus detected and the severity of the symptoms [ ] . nevertheless, no consensus has been reached yet regarding a threshold level that could actually predicts clinical severity. targeting the envelop gene upe is recommended with confirmatory testing for orf a or b or the n gene. if results diverge, sequencing is sometimes required to obtain conclusive results [ ] . today, an increasing number of commercial tests are becoming available (altona diagnostics, fast track diagnostics, primerdesing ltd.) some even with a time to results of less than hour (biofire-biomérieux). some of these tests are point-of-care, or can be performed in bsl facilities or a standard laboratory following sample neutralization in a bsl facility. these commercial tests must always be validated before use to check their sensitivity and compare their performance with reference methods. as with any other acute viral infection, antibodies can only generally be detected about days after the onset of symptoms. in some patients, especially those with severe infections, the time interval to antibody detection may be even longer [ ] . serological testing is therefore of little help for the initial diagnosis of symptomatic patients, but can be useful for epidemiological investigations. the highly immunogenic s and n viral proteins are widely used targets for serological tests and are found on all coronaviruses. various approaches have been developed: serum neutralization assays [ ] , microarrays [ ] , or more recently elisa confirmed by a microneutralization test [ ] . all methods are technically complex and require a high level of expertise that restrict their use to a few highly specialized facilities. the first cases of infection with mers-cov were reported in [ ] . hospital-acquired mers-cov infections have been described worldwide and represented a third of all cases reported in saudi arabia in the early stages of the epidemic [ , , ] . clustered hospital-acquired infections were frequently observed during the first outbreaks and probably contributed to spreading the disease from the primary site of virus infection to the whole arabian peninsula, the most striking example of hospital-acquired outbreak being the korean outbreak in [ ] . care providers are often affected and represent - % of cases [ ] [ ] [ ] [ ] [ ] [ ] [ ] . most of the cases are described in middle east countries, in particular saudi arabia ( %), with a predominance of male patients ( - % in various studies) and a mean patient age ranging from to years [ , , ] . comorbidities are found in - . % of patients, in particular diabetes and high blood pressure, followed by other heart conditions and finally obesity [ , , , ] . the mean incubation time is to . days. the generation interval (time between the onset of symptoms of the first case and those of the second case) is . days, which is identical to that of the respiratory syncytial virus (rsv) but threefold more than the influenza virus [ , [ ] [ ] [ ] . the main challenge of mers-cov infection is the absence of specific clinical features for differential diagnosis with other viral respiratory diseases [ , ] . this difficulty, combined with precautionary action taken to avoid potential secondary contamination with mers-cov [ ] , can result in medical confusion and inappropriate patient management due to prolonged, difficult isolation that makes it impossible to perform the necessary complementary tests while waiting for pcr results [ ] . the clinical features of mers-cov infection are extremely variable, ranging from an absence of symptoms ( - % of cases) to a flu-like syndrome, pneumonia and acute respiratory distress syndrome (ards) [ , ] . the three most frequent symptoms are: fever ( % [iqr: - ]), cough ( % [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] ), and dyspnea ( % ). many other secondary symptoms have been reported, such as sputum production ( %), odynophagia ( %), digestive system signs ( %), hemoptysis ( . %), myalgia ( %) and headache ( %) [ , , , ] . diarrhea is significantly more frequent in patients infected with mers-cov than in patients with another acute, febrile respiratory conditions [ ] . severe mers is characterized predominantly by ards, acute kidney failure, and in the most severe cases, by multiple organ failure that can be fatal [ , ] . one third of patients develop pneumonia and % develop ards [ ] . the median time to respiratory failure is days after the onset of symptoms. depending on studies, to % of hospitalized patients are admitted to an intensive care unit (icu) [ , ] . since the first mers outbreak, who had documented, in october , cases of mers-cov infection confirmed by laboratory testing and related deaths in different countries. the retrospective fatality rate varies between outbreaks, ranging from . to % [ , , , , ] . the mortality rate of . % observed for the korean outbreak is probably the most reliable epidemiologically due to the comprehensive investigations carried out [ ] . the death rate is highest among patients admitted to an icu, ranging from % to % [ , ] . in the only cohort study performed in saudi arabia, the fatality rate for mers-cov patients was of only % ( / ). however, the patients of this cohort were younger, had less symptoms, showed less radiological features and only % were admitted to an icu [ ] . the findings of the latter study diverge therefore with the situations observed in other hospitals, but are perhaps a better reflection of the infection profile in the general population in which younger subjects are less symptomatic and therefore less frequently admitted to hospital. the time interval between the onset of symptoms and death ranges from . to days [ , , ] . finally, co-infection with other respiratory viruses, in particular influenza, has been described although the impact of such combined infections have not been evaluated [ , ] . co-infections with bacteria have also been reported in the patients developing the most severe disease [ , ] . there are no specific laboratory findings related to mers-cov infection. nevertheless in patients with acute respiratory infection in mers-endemic areas, mers-cov infections have been associated with normal leukocyte and/or polymorphonuclear neutrophil counts but elevated transaminases [ , ] . moreover, hyperleukocytosis, lymphocytopenia, thrombocytopenia, hypoalbuminemia, elevated serum creatinine, ldh and crp levels, and hypoxemia (pao /fio < ) have been repeated reported in mers-cov infected patients and are associated with severity and death [ , ] . imaging (chest x-ray and sometimes chest ct) has revealed infection-related features in - % of cases. the lesions observed are uni-or multi-focal ground glass opacifications, of subpleural and lower lobe predominance, with sometimes bilateral bi-basal involvement or features of organizing pneumonia [ , , , ] . mortality is highest in elderly, male patients with comorbidities, especially diabetes [ , , ] . patients from saudi arabia and the middle east have an increased mortality rate compared with patients from korea or other countries [ , ] . in contrast, being a medical professional significantly reduces the risk of mortality [ , ] . other factors associated with a higher mortality risk have been described in various studies: digestive symptoms, prolonged delay between the onset of symptoms and admission to hospital, smoking, low blood pressure, impaired gas exchange, leukopenia, anemia, disturbance of liver or kidney function, use of mechanical ventilation and prolonged stay in the icu [ , ] . for the korean outbreak in , the independent risk factors for mortality were: age > years, dyspnea, diabetes, chronic lung disease, systolic blood pressure at admission < mmhg, hyperleukocytosis at admission (> , /mm ) and the use of mechanical ventilation [ ] . positive pcr results for mers-cov in blood at diagnosis are associated with an increased risk of requiring mechanical ventilation, extracorporeal membrane oxygenation (ecmo) or to lead to death [ , ] . the lack or delayed detection of mers antibodies (elisa igg and iga, or prnt) in the blood or airways is a poor prognostic factor [ , ] . it should however be noted that no seroconversion is observed in asymptomatic mers-infected patients [ ] . finally, the mers-cov viral loads in distal lung samples were higher among deceased patients [ ] . in a study including patients in a tertiary referral hospital in south korea: • the predictive factors for pneumonia in mers-cov patients were: age > years, body temperature > . • c on day , platelet counts < , /mm , lymphocytopenia (< /mm ), crp ≥ mg/l and high viral loads (ct value < . ); • the predictive factors for respiratory failure were male sex, high blood pressure, thrombocytopenia, lymphocytopenia, hypoalbuminemia < g/l and crp ≥ mg/l. the patients with at least two, one and none of the predictive pneumonia factors developed pneumonia in %, % and % of cases, respectively [ ] . several therapeutic options targeting various viral elements are currently available or under development (fig. ) [ ] . the different classes of available treatment are (i) immunotherapy with specific anti-mers-cov antibodies, (ii) molecules with antiviral activity, (iii) symptomatic treatment. few molecules have shown real curative action and the reports in the literature generally describe isolated cases or small series of cases. more studies have focused on associated treatment and supportive care. at this time, preventive therapies are still in preclinical stages. the efficacy and safety of plasma from convalescent patients have not been assessed. three separate reports concluded that such therapeutic approaches were inappropriate [ ] . one trial is listed on www.clinicaltrials.gov. two cases of therapy with intravenous polyclonal iggs have been reported. in one of them, the iggs originated from donors in regions negative for mers specific antibodies. several monoclonal antibodies were tested and seemed to show anti-mers-cov activity in vitro [ ] . no clinical trials are currently underway. recently, a phase i placebo-controlled, dose escalation study evaluated the efficacy of polyclonal iggs produced by transchromosomal cattle with human immunoglobulin genes immunized with the mers-cov spike (s) protein [ ] . the primary outcome of tolerance to a single dose was reached. the secondary pharmacodynamic endpoint (serum neutralization activity) showed efficacy with a dose of mg/kg. no phase ii trials are currently underway. a phase i study has been registered to assess the immunogenicity and tolerance of a combination of two monoclonal anti-mers-cov antibodies. the study has not yet started recruiting patients. infection with mers-cov reduces the host's interferon response. mers-cov is times more sensitive to ifn-␣. treatment with ifn-␣ has been reported for many clinical cases and several retrospective cohort studies have been performed, in combination with ribavirin, lopinavir or mycophenolate mofetil (mmf). none of these studies have demonstrated increased overall survival. one study reported increased survival at d but not at d for critically ill intubated and ventilated patients [ ] . a ifn/mmf combination trial is currently underway (see below). high doses of ribavirin have shown anti-mers-cov activity in vitro. ribavirin has been used to treat patients in saudi arabia as well as in france for the most severe cases managed in icus [ ] . no significant effects were demonstrated either on the mortality rate or the time spent in the icu. ritonavir-boosted lopinavir has shown efficacy against mers-cov in vitro. as a result, the fda has extended the indications of lopinavir to patients infected with mers-cov. two case reports (in greece and korea) have described improvement in patients treated with lopinavir, type interferon and ribavirin [ ] . a phase ii-iii clinical trial is registered on clinicaltrials.gov. the aim of this study is to evaluate the feasibility, efficacy and safety of the combination lopinavir/ritonavir/recombinant ifn␤- b vs. a placebo in patients with confirmed mers receiving optimal symptomatic care. chloroquine is among the molecules approved by the fda following in vitro studies. no clinical data or studies support its use in vivo at the present time. in vitro, anti-mers-cov activity has been demonstrated for doses of nitazoxamide that could be reached with two daily oral doses. no clinical data or studies support its use in vivo at the present time [ ] . in vitro, anti-mers-cov activity has been demonstrated for doses of mmf that are acceptable for use in humans. mmf seems to show a synergistic effect with ifn-␤ b in vitro [ ] . but in a non human primate common marmosets model, animals treated with mmf developed more severe lesions and showed a higher case fatality rate compared with untreated animals [ ] . in contrast with animal model, the combination ifn-␤ b/mmf was administered to patients in saudi arabia. all the patients survived but had lower apache ii scores that other patient groups [ ] . alisporivir has been shown to provide additive in vitro anti-mers-cov activity when used in combination with ribavirin. no clinical data or studies support its use in vivo at the present time [ ] . silvestrol is a molecule of the flavagline family found in plants. it binds to eif a and enhances the affinity of eif a for mrna. this blocks helicase activity and inhibits protein translation. a recent in vitro study demonstrated that silvestrol has anti-mers-cov activity [ ] . no clinical data or studies support its use in vivo at the present time. corticosteroid therapy is currently the most widely studied therapeutic option. in a retrospective study, arabi et al. [ ] compared the outcome of patients with confirmed mers-cov infection managed in an icu setting and treated with ( ) or without ( ) corticosteroid therapy. the overall fatality rate was %. univariate analysis showed that mortality in the icu, during the hospital stay or at days was higher in the corticosteroid group. then, following adjustment using a marginal structural model for causal inference, corticosteroid therapy was shown not to be associated with mortality, but delayed virus clearance. these findings, together with the absence of any description of the adverse effects caused by corticosteroid treatment, argue against the use of corticosteroids. a retrospective study was recently carried out in saudi arabia in mers-cov patients with refractory respiratory failure [ ] . the patients were included in the study from to in five icus. the study consisted of two patient groups: ecmo versus conventional treatment. the primary endpoint was inhospital mortality. secondary endpoints included the length of stay in the icu and in hospital. thirty-five patients were included: were treated with ecmo and received conventional care. both groups had similar baseline characteristics. inhospital mortality was lower in the ecmo group ( vs. %; p = . ) although they stayed longer in the icu (median stay of days vs. days; p < . ). the overall time in hospital was similar in both groups (median stay of vs. days; p = . ). in addition, patients in the ecmo group showed improved pao /fio values at and days after admission into the icu ( vs. , and vs. , respectively; p < . ), and lower levels of vasoactive amines at d and d ( vs. %, and vs. %, respectively; p < . ). the results of this study support the use of ecmo as salvage treatment for mers patients with respiratory failure, as is the case for other respiratory infections. two trials with candidate vaccines are currently registered at https://clinicaltrials.gov/ct /home. a phase-i clinical trial on healthy volunteers was set up to evaluate the safety and immunogenicity of a plasmid dna vaccine (gls- ) that expresses the s protein of mers-cov. this trial was planned to last one year and started in . no results are available yet. a second phase-i trial was started by oxford university in january . it uses a chimpanzee adenovirus vector containing the mers-cov s protein gene [ ] . patient inclusion is currently underway. many other candidate vaccines using various different technologies are at a less advanced stage of development. the mers epidemic started in . in contrast with sars-cov that disappeared years after it first appeared, mers-cov continues to persist in the middle east years later. although the disease has not become pandemic, outbreaks have occurred worldwide. today, it is impossible to predict with certainty whether mers-cov will disappear or continue to remain a threat for human populations. efficient vaccine development for host ani-mals and humans could play a key role in tilting the balance from potentially-pandemic to mers-cov elimination. furthermore, the epidemiological and viral determinants of the emergence of mers-cov in the middle east are difficult to comprehend, due to the high seropositivity rate of african dromedary camels but no similar disease in local human populations. the constant increase of transcontinental travel, in particular towards the main focal points of mers outbreaks with religious pilgrimages and mass tourism, raises the problem of the management of patients suspected of mers-cov infection and the absence of efficient treatment options to this date. the main problem in non-epidemic countries is to detect a mers-cov case among a great number of non-mers patients. in france, with the exception of the first cases, no further cases have been detected. the current strategy is to isolate any suspicious cases as rapidly as possible to contain the infection and prevent local outbreaks as seen in south korea. the ability to rapidly test patients suspected to have mers-cov infection is the cornerstone of this strategy. the experience gained over the last few years by the health community will also help deal with any respiratory infections that will emerge in the future. the authors declare that they have no competing interest. isolation of a novel coronavirus from a man with pneumonia in saudi arabia middle east respiratory syndrome coronavirus (mers-cov). who mers-cov outbreak following a single patient exposure in an emergency room in south korea: an epidemiological outbreak study world health organization. consensus document on the epidemiology of severe acute respiratory syndrome (sars) molecular evolution of human coronavirus genomes genomic characterization of a newly discovered coronavirus associated with acute respiratory distress syndrome in humans severe respiratory illness caused by a novel coronavirus who | background and summary of novel coronavirus infection-as of comparative analysis of twelve genomes of three novel group c and group d coronaviruses reveals unique group and subgroup features presence of middle east respiratory syndrome coronavirus antibodies in saudi arabia: a nationwide, cross-sectional, serological stud human infection with mers coronavirus after exposure to infected camels, saudi arabia mers coronavirus neutralizing antibodies in camels antibodies against mers coronavirus in dromedary camels risk factors for mers coronavirus infection in dromedary camels in co-circulation of three camel coronavirus species and recombination of mers-covs in saudi arabia genomic characterization of a newly discovered coronavirus associated with acute respiratory distress syndrome in humans mers-cov accessory orfs play key role for infection and pathogenesis host species restriction of middle east respiratory syndrome coronavirus through its receptor, dipeptidyl peptidase host cell entry of middle east respiratory syndrome coronavirus after two-step, furin-mediated activation of the spike protein a structural analysis of m protein in coronavirus assembly and morphology east respiratory syndrome coronavirus (mers-cov)-update. who transmission characteristics of mers and sars in the healthcare setting: a comparative study new case of mers-cov identified in the united kingdom middle east respiratory syndrome coronavirus (mers-cov): prevention in travelers respiratory tract samples, viral load, and genome fraction yield in patients with middle east respiratory syndrome association of higher mers-cov virus load with severe disease and death, saudi arabia a roadmap for mers-cov research and product development: report from a world health organization consultation presence of middle east respiratory syndrome coronavirus antibodies in saudi arabia: a nationwide, cross-sectional, serological study specific serology for emerging human coronaviruses by protein microarray inclusion of mers-spike protein elisa in algorithm to determine serologic evidence of mers-cov infection clinical features and viral diagnosis of two cases of infection with middle east respiratory syndrome coronavirus: a report of nosocomial transmission case characteristics among middle east respiratory syndrome coronavirus outbreak and non-outbreak cases in saudi arabia from to clinical presentation and outcomes of middle east respiratory syndrome in the republic of korea mers-cov outbreak in jeddah-a link to health care facilities mers outbreak in korea: hospital-to-hospital transmission predictors of mers-cov infection: a large case control study of patients presenting with ili at a mers-cov referral hospital in saudi arabia the predictors of -and -day mortality in mers-cov patients middle east respiratory syndrome coronavirus infections in health care workers estimating survival rates in mers-cov patients and days after experiencing symptoms and determining the differences in survival rates by demographic data, disease characteristics and regions: a worldwide study prevalence of comorbidities in the middle east respiratory syndrome coronavirus (mers-cov): a systematic review and meta-analysis middle east respiratory syndrome coronavirus in al-madinah city, saudi arabia: demographic, clinical and survival data hospital outbreak of middle east respiratory syndrome coronavirus middle east respiratory syndrome a comparative study of clinical presentation and risk factors for adverse outcome in patients hospitalised with acute respiratory disease due to mers coronavirus or other causes rapid risk assessment: severe respiratory disease associated with middle east respiratory syndrome coronavirus (mers-cov), nd update clinical management of respiratory syndrome in patients hospitalized for suspected middle east respiratory syndrome coronavirus infection in the paris area from outbreak of middle east respiratory syndrome coronavirus in saudi arabia: a retrospective study clinical course and outcomes of critically ill patients with middle east respiratory syndrome coronavirus infection middle east respiratory syndrome coronavirus infection: a short note on cases with renal failure problem state of knowledge and data gaps of middle east respiratory syndrome coronavirus (mers-cov) in humans middle east respiratory syndrome coronavirus: a case-control study of hospitalized patients clinical aspects and outcomes of patients with middle east respiratory syndrome coronavirus infection: a single-center experience in saudi arabia serologic responses of mers-coronavirus-infected patients according to the disease severity the impact of co-infection of influenza a virus on the severity of middle east respiratory syndrome coronavirus critically ill patients with the middle east respiratory syndrome: a multicenter retrospective cohort study high fatality rates and associated factors in two hospital outbreaks of mers in daejeon, the republic of korea ifn-( a or ifn-( a in combination with ribavirin to treat middle east respiratory syndrome coronavirus pneumonia: a retrospective study viral rna in blood as indicator of severe outcome in middle east respiratory syndrome coronavirus infection comparative and kinetic analysis of viral shedding and immunological responses in mers patients representing a broad spectrum of disease severity predictive factors for pneumonia development and progression to respiratory failure in mers-cov infected patients prevention and treatment of respiratory viral infections: presentations on antivirals, traditional therapies and host-directed interventions at the th isirv antiviral group conference feasibility of using convalescent plasma immunotherapy for mers-cov infection, saudi arabia current treatment options and the role of peptides as potential therapeutic components for middle east respiratory syndrome (mers): a review safety and tolerability of a novel, polyclonal human anti-mers coronavirus antibody produced from transchromosomic cattle: a phase randomised, double-blind, single-dose-escalation study a review of treatment modalities for middle east respiratory syndrome corticosteroid therapy for critically ill patients with the middle east respiratory syndrome virological and serological analysis of a recent middle east respiratory syndrome coronavirus infection case on a triple combination antiviral regimen nitazoxanide, a new drug candidate for the treatment of middle east respiratory syndrome coronavirus treatment with lopinavir/ritonavir or interferon-( b improves outcome of mers-cov infection in a nonhuman primate model of common marmoset treatment outcomes for patients with middle eastern respiratory syndrome coronavirus (mers cov) infection at a coronavirus referral center in the kingdom of saudi arabia alisporivir inhibits mers-and sars-coronavirus replication in cell culture, but not sars-coronavirus infection in a mouse model broad-spectrum antiviral activity of the eif a inhibitor silvestrol against corona-and picornaviruses extracorporeal membrane oxygenation for severe middle east respiratory syndrome coronavirus chadox and mva based vaccine candidates against mers-cov elicit neutralising antibodies and cellular immune responses in mice the chapters on the origin, emergence, structure, transmission mechanisms, prevention and diagnostic methods were mainly written mb, nh, and bv.bv produced the figures. the chapters on clinical presentation, prognosis and available treatment options were mainly written by ab and cb.all authors read, amended and agreed with the entire final manuscript. key: cord- - o nr authors: al-rasheedi, mabrouk; alhazmi, yasir; mateq ali, alreshidi; alrajhi, maha; samah alharbi, nayef; alsuhaibani, somayah; mohammed, alrashidi; alharbi, ghaleb title: public and healthcare providers awareness of coronavirus (covid- ) in qassim region, saudi arabia date: - - journal: saudi j biol sci doi: . /j.sjbs. . . sha: doc_id: cord_uid: o nr background the rapid and extensive spread of the covid- pandemic has become a major cause of concern for both general public and healthcare profession. objective the aim of this study is to analyze and evaluate the awareness of both the general public and healthcare providers in qassim region in saudi arabia. method a cross-sectional study was conducted randomly in different shopping malls in qassim region from th of february to th of march, . all participants have answered the designed questionnaire. the structured questionnaire recorded demographics and awareness of both public participants as well as health care providers. result a total of participants have answered the designed questionnaire, out of which participants were males ( . %) and were females ( . %). overall, ( %) out of the participants are aware of covid- , and ( %) have recognize it as a respiratory disease and % of the participants have recognized it as a contagious disease. around % of the participants were able to recognize the correct incubation period of the virus. participants of the age group - showed higher awareness level than other age groups (p value = . ). in addition, government employees showed higher awareness level than other profession groups (p= . ). results showed significant positive correlation between the recognition of high-risk groups, reliable source of information, infection symptoms, disease prevention and available treatments. conclusion general public and health care professionals from qassim region showed adequate awareness of covid- . however, there is a strong need to implement periodic educational interventions and training programs on infection control practices for covid- across all healthcare professions. covid- is the main causative agent of the newly emerged communicable disease, and it is more commonly referred to as coronavirus (who, a) . it has been officially named the severe acute respiratory syndrome coronavirus , or sars-cov- (originally, this was called -ncov) (who, a , cdc, . in , there was a spate of cases of respiratory illness that rapidly turned into an epidemic in wuhan city, hubei province of china (gallegos, a., ) . the first report of this was made to the world health organization (who) on the st (the new york times, ). approximately one month later, on the th of january , the who announced that the outbreak of covid- was being proclaimed a global health emergency (the new york times, .). in addition, since the st of january , the who has been publishing daily 'situation reports' on its website (www.who.int) to update disease facts, numbers (cases, deaths, and recoveries, by country), and other related information (the new york times, .). there are three main symptoms of covid- , and several others that are less frequently experienced by people (madjid et al., ) . the main symptoms are fever, cough, and shortness of breath, while the less common symptoms include muscle pain, anorexia, a general feeling of unwellness, sore throat, nasal congestion, dyspnea, and headache (madjid et al., ) . recently, new symptoms have been raised such as losing taste and smell (klopfenstein et al, ) . once an individual has been exposed to the virus, symptoms can manifest from anywhere between two and fourteen days (madjid et al., ) . for the majority of individuals who contract covid- , only minor to middling cases of respiratory illness will be experienced, and they will not require any special medical interventions to recover. conversely, a more severe illness has a high probability of developing if covid- is contracted by the elderly or those with underlying medical conditions (such as cancer, cardiovascular disease, chronic respiratory disease, and diabetes) (madjid et al., ) . the main way in which covid- is transmitted is via saliva or nose discharge droplets that travel when an individual carrying the disease coughs or sneezes (who, a) . individuals can acquire the disease also through touching any contaminated surface and touching their eyes, mouth, nose or general face area (who, b) . although can be killed by disinfectants, it is believed that it will survive on un cleaned, contaminated surfaces for a couple of hours (who, b) . it has been suggested that aerosol-generating medical procedures may spread sars-cov- by means of airborne transmission (who, d) . currently, there is no definitive treatment or vaccine for covid- . nevertheless, there are numerous clinical trials being conducted all over the world that are attempting to identify possible treatments for the disease. the who will report on clinical findings as and when tangible results become available (who, a , ecdc, a . the international community is united in working on finding vaccines against covid- and upwards of ten vaccines are currently being tested through clinical trials -with some studies having already entered phase ii. in addition, a number of wide-ranging clinical trials, conducted at more than one center, are being carried out, using a rigorous methodological model to evaluate prospective methods of treatment which will be effective against covid- . (ecdc, c). in the light of the absence of any effective treatment and with the clearly identified mode of transmission, awareness of essential information of the disease is the most powerful tool that individuals can have against the virus. being informed about the causes of covid- and the way it spreads is the optimum means of avoiding it and decreasing transmission rates (cdc, ). the key advice from the who to prevent the spread of covid- is that people should remain at home, ensure social distancing measures are being taken, wash their hands frequently with soap and water, and frequently clean objects and surfaces that are touched on a regular basis (who. b); therefore, effective awareness training in workplaces will be essential in the fight to halt the spread of the disease. the first step to raise people defense against covid- is education (interactive service, ). people should be informed about disease symptoms, actions to take to protect themselves and those around them. it is also important to inform people of what kind of actions should they take in case of getting in contact with someone exposed to the virus (interactive service, ) the kingdom of saudi arabia introduced preventative measures before any national fatalities from covid- were reported, and prior to the virus being formally declared a global pandemic (alshammari et al., ) . the saudi government thus imposed a strict curfew, reinforced by financial penalties for anyone who ignored the rules (algaissi et al., ) . in addition, a new app, the tawakkalna, was launched by the ministry of health and the ministry of the interior, to allow people to meet their needs and plan their journeys during the curfew period (spa, ) . the app also provided up to date information on highly-contagious and remote areas of the country (spa, a) . the ministry of health decided to hold daily meetings, to update the public about the current situation in the country, as well as across the world, to share new information on the virus and to respond to any questions (spa, b) . in addition, the ministry of health set up an information helpline (accessible by dialing ) so that people could ring in for general advice on covid- , as well as ask specific questions (moh, ). a covid- website was created, which lists all active and recovered cases in every city in ksa on a daily basis, and social media was used to send messages and raise levels of public awareness of dashboard saudi arabia, ). to the best of our knowledge, there has yet to be a study conducted specifically in this region on peoples' awareness of covid- . therefore, in order to fill this research gap, the aim of this paper was to evaluate the knowledge and awareness of both the general public and healthcare providers in qassim region in saudi arabia. this descriptive, cross-sectional, and randomized study was conducted in qassim region inside shopping malls from th of february to th of march . all participants were selected from qassim province, most of whom were from buraydah, the province's capital. qassim is located in the center of saudi arabia, and it has around . million inhabitants. the following inclusion criteria were applied in this study: first, participants had to be adults (i.e., older than years of age) either saudi or non-saudi; second, participants had to reside in qassim region from general papulation and health care providers; and third, participants needed to provide voluntary and sign an informed consent prior to participating. participants who did not meet these criteria were excluded from the study. data were obtained in-person using a structured questionnaire after the participants had signed the consent form. a pilot study was undertaken to validate the questionnaire, and a panel of three domain-specific experts was used to test the data collection instrument. the questionnaire was used to gather participants demographics and public participants awareness as well as healthcare providers awareness of the pandemic. microsoft excel was used to analyze data from participants, as well as statistical package for the social sciences (spss) version . excel was used for data entry and data representation purposes and spss was used for running statistical analyses. different categorical and quantitative variables were identified, and data were cleansed before running statistical analyses, and missing data and typographical errors were checked. using spss, counts and percentages were examined for the categorical variables, and descriptive statistics were undertaken for the quantitative variables. inferential statistics were also used to address the study's main research questions. the parametric assumptions associated with all variables were tested. different comparisons were performed using the mann-whitney u test for independent twogroup variables, while for more than two groups, the kruskal-wallis signed rank test was employed. throughout this study, data are presented as median and quartiles, and p-values are considered statistically significant at < . . a total of participants have answered the designed questionnaire, out of which participants were males and were female with percentage of . % and . % respectively. four age groups have been identified among the participants (< , - , - , > ), with around % of the second age group from - . educational level varied from intermediate education to postgraduate studies while the majority ( %) had ba or bsc. profession showed variation between private, governmental, health and other sectors. results of the participants demographics is presented in (table and fig. ). this part of the questionnaire composed of nine checkbox questions and responders should select as much correct choices as possible. number of correct choices for each participant and number of participants who chose every choice within each question were used to represent the awareness of covid- detailed information (table ) . results showed that the highest awareness rate was recorded in the question of the reliable source of information where % of the participants have recognized all reliable sources while only % have not recognized any reliable source (table ) . a total % of participant have recognized who as the most reliable source of information about covid- while healthcare professionals came at second with %. other options were selected with less than % of the participants (fig. ) . participants showed the second-high awareness towards the recognition of the highrisk groups with % of participants have chosen all high-risk groups, while only % of the participants have not recognized any group. elderly people, patients with chronic conditions, health care workers, was the arrangement of the high-risk groups with around %, %, % of selection respectively (table and fig. ). mode of transmission was only recognized through human to human transmission with % while on other side no participant has recognized contacting contaminated surfaces as a transmission mode (table and fig. ) . responses varied towards the recognition of disease symptoms were out of the eight known symptoms, only % were able to choose all symptoms while % where able to recognize seven of them and the highest rate was between and symptoms with around % of participants. a total of % have marked fever and shortness of breath to be the most common symptoms followed by cough ( %), sore throat ( %), tiredness ( %), muscle pain ( ), the rest symptoms were chosen by less than % (table and fig. ). the lowest awareness rate was towards the long-term complications of the disease where % of the participants have recognized none of the long-term complications while % were able to recognize only one complication out of the three listed complications. pneumonia was the highest marked complication by %, followed by death with %, while kidney failure was recognized by only % of the participants (table and fig. ). out of six measures to prevent covid- spread, % of the participants have denoted the six measures followed by % with five measures recognized. the highest recognized measures among the participants were avoid travelling and gathering, sanitizers and cleaning materials usage, washing hands with soap for seconds with %, %, % respectively (table and fig. ). preparation to fight the covid- showed a moderate awareness about possible options where over % were able to find more than two measures out of the six correct measures. only % were able to identify the six measures correctly followed by % with five measures identified. it is noteworthy that this question in line with the spread prevention question showed % of participants failed to recognize at least one correct choice. general hygiene rules were the most marked measure with % of participants, followed by cover when coughing and sneezing and avoid contact with sick people with %, avoid travelling to infected areas with %, frequent hand wash %. it is worth mentioning that avoid raw animals was marked by % of participants, while avoid places handling animals was marked by % of participants (table and fig. ). responses towards the treatment for covid- showed that % were not able recognize the proper handling of the disease while % were able to check one measure and % were able to find the two correct measures listed in the questionnaire. it is noteworthy to mention that all participants were aware of the fact that there is no vaccination yet for covid- and % knew that there is no treatment as well while only % were able to recognize supportive treatment as a method to control or improve chances of disease control (table and fig. ). preparation of fighting covid- among medical workers showed that % were non health workers while among medical workers, results showed that % were able to recognize the six important measures for preparation against the virus while around % of medical workers were not able to recognize any correct measures. out of the medical workers who responded to our questionnaire, % has recognized check supplies for emergencies as the first priority followed by contact international centers as cdc and who followed by evaluation of equipment and ventilators as the highest priority while alternative supplying checking came at last position with % (table and fig. ). investigating differences among different groups of the participants was done for sex, age, educational level and profession. parametric assumptions were tested, and data showed significant violation against assumptions. differences between different genders were examined using mann-whitney signed rank test while differences among age, education, profession groups were tested using kruskal-wallis one way signed rank test. results showed that there were no significant differences among different groups for all questions except for two questions. results showed that there were significant differences of awareness levels among different groups of age and profession in response to the identification of the high-risk groups. participants of the age group - showed higher awareness than other age groups while government employees showed higher awareness level than other profession groups. results showed that there were significant differences of awareness levels among different groups of age and sex in response to the identification of covid- treatment. participants of the age group - showed higher awareness than other age groups while females showed higher awareness level than males in response to the treatment of covid- ( . . correlation among awareness levels of covid- detailed information. as parametric assumptions have been violated, non-parametric spearman correlation was investigated among awareness levels of covid- specifics. results showed significant positive correlation between high risk groups recognition, reliable source of information, infection symptoms, disease spread prevention and covid- available treatments. while the reliable source of information awareness was positively correlated with all other questions except for the long-term complication's awareness. the lowest correlations were found between the awareness level of the long-term complications and the available covid- treatment in one side and all other questions on the other side. long term complications awareness level was only table . awareness level comparisons among different groups of sex (mann-whitney signed rank test), age, education and profession (kruskal-wallis one way signed rank test). *denotes significance level at p value < . , **denotes significance level at p value < . correlated to the awareness level of disease symptoms while treatment awareness level was correlated to high risk group, information source and disease spread prevention (table ). the purpose of this study was to evaluate the awareness of healthcare professionals and the general public regarding covid- in qassim region, kingdom saudi arabia with focusing on both general awareness and detailed information. although the first patient was diagnosed in qassim region on nd march , the subgroup analysis revealed that no significant differences existed between the different groups for every question, except for two questions. firstly, a significant difference was identified based on age group, and secondly, a significant difference was also identified for profession. specifically, young individuals who worked in professional positions were associated with a greater awareness of the complications of covid- . to the best of our knowledge, this is the first study that has sought to evaluate covid- awareness in saudi healthcare professionals and the general public in qassim region. in healthcare professionals, results indicate that most are aware of the critical details that will aid in the fight in the time of the pandemic. these results are consistent with a najran-based cross-sectional study of the knowledge and attitudes towards the middle east respiratory system coronavirus (mers-cov) in healthcare professionals in primary healthcare centers and hospitals (asaad et al., ) . specifically, the study noted that healthcare professionals had a satisfactory level of knowledge about the disease (asaad et al., ) . however, other ksa-based studies have been conducted in which it has been found that awareness for emerging infectious diseases is low, which highlights the importance of examining this issue further (al-mohaissen, m., ). finally, a noteworthy limitation of this study is that the sample group may not have been representative. for example, most of the participants were members of the young generation, meaning that the generalizability of these results to other parts of the ksa is low. the present study found that healthcare professionals and members of the general this study indicates that there is an urgent need to implement regular educational interventions and training initiatives on infection control practices for covid- for healthcare professionals. for example, webinars could be held for members of the healthcare profession, including administrators and hospital managers, and it may be also beneficial to extend these initiatives to the general public. preparedness and response to covid- in saudi arabia: building on mers experience awareness among a saudi arabian university community of middle east respiratory syndrome coronavirus following an outbreak importance of early precautionary actions in avoiding the spread of covid- : saudi arabia as an example. saudi pharm knowledge and attitudes towards middle east respiratory sydrome-coronavirus (mers-cov) among health care workers in south-western saudi arabia cdc, . how covid- spreads covid dashboard saudi arabia vaccines and treatment of covid- coronavirus disease (covid- ) in the eu/eea and the ukeighth update vaccines and treatment of covid- who declares public health emergency for novel coronavirus general authority for statistics kingdom of saudi arabia. . service guide interactive service. . coronavirus (covid- ) awareness training new loss of smell and taste: uncommon symptoms in covid- patients on potential effects of coronaviruses on the cardiovascular system hand hygiene practices among indian medical undergraduates: a questionnaire-based survey moh: call ( ) service center for inquires about novel coronavirus nih clinical trial of hydroxychloroquine, a potential therapy for covid- clinical characteristics of covid- patients with digestive symptoms in hubei, china: a descriptive, cross-sectional, multicenter study sfda approved who solidarity clinical trial for covid- to be conducted in saudi arabia by the ministry of health critically ill patients with covid- with convalescent plasma sdaia launches tawakkalna app to facilitate the issuance of movement permits electronically during the curfew period spa. b. covid- follow-up committee holds meeting the new york times. . w.h.o. declares global emergency as wuhan coronavirus spreads who. b. key messages and actions for covid- prevention and control in schools who announces covid- outbreak a pandemic transmission of sars-cov- : implications for infection prevention precautions key: cord- -fznw bbq authors: alhazmi, amani; ali, maha hamed mohamed; mohieldin, ali; aziz, farah; osman, osman babiker; ahmed, waled am title: knowledge, attitudes and practices among people in saudi arabia regarding covid- : a cross-sectional study date: - - journal: j public health res doi: . /jphr. . sha: doc_id: cord_uid: fznw bbq background: the general population’s compliance with preventive measures and legislation is mainly influenced by their knowledge level, attitude, and practices. this study assessed the knowledge, attitude, and practices of public residents towards corona virus disease- preventive measures in saudi arabia. design and methods: this is a cross-sectional study; it used a validated cross-sectional online survey that received responses from saudi administrative regions. results: there were participants who completed the study ( % females; . %, university education). knowledge level, attitude, and practices towards corona virus disease- were . %, . %, and . %, respectively. the knowledge subscales showed that ( . %) participants knew the system targeted by the virus, . % and . % knew the causative agent and symptoms, ( . %) participants knew the transmission modes, and ( . %) participants knew about the complications. the attitude subscales included ( . %) participants who had dealt with an infected person, ( . %) participants who isolated in a health facility, ( . %) participants who knew about hand washing, and ( . %) participants who thought the virus spread through home delivery. the practice subscales included ( . %) participants who properly disposed of gloves and tissues and ( . %) participants who reported safe practices when coughing or sneezing. conclusions: this study showed satisfactory knowledge, attitude, and practice towards corona virus disease- in saudi arabia. the educational level is a dominant influencing factor for knowledge, attitude, and practice. in , the world health organisation (who) stated that a new coronavirus strain had been identified in wuhan city, china, and it was recognised as a novel coronavirus that caused new types of respiratory infections. , the disease was later called the coronavirus disease . , coronavirus family strains can cause diseases that are known as respiratory infections including the common cold and up to serious infections such as middle east respiratory syndrome (mers) and severe acute respiratory syndrome (sar-cov). the most recently discovered viruses that causes coronavirus are rar-cov and covid- . this virus may remain on surfaces for a few hours or up to many days; this varies according to different conditions based on types of surfaces, temperatures, and humidity levels. , covid- viruses lead to severe acute respiratory syndrome coronavirus- (sars-cov- ), which is highly contagious. in response to covid- , the who described covid- as a pandemic. the causative agent in covid- is mainly transmitted through respiratory droplets from infected people; by contact with contaminated surfaces; through healthcare-associated exposure among those who provide direct care for covid- patients, work together, share the same environments, are transported along with others who have covid- , and are involved with patients in any kind of transportation; and by people who live in the same houses as covid- patients. a confirmed covid- case is defined as a suspected case with laboratory confirmation of covid- infection. , important knowledge gaps exist such as pre-symptomatic and asymptomatic transmission, the effects of covid- transmission on different age groups, conditions leading to super-spreading events, epidemiological time delays (onset to illness, to case detection delays or to hospitalisation), environmental conditions related to increased transmission (temperature, humidity, and seasonality), the spectrum of clinical complications, the clinical manifestations of slight to severe disease, the severity that is mediated by demographic factors (gender, age, or other groupings), groups that are at high risk of severe infection, social distancing measures, the effectiveness of international travel in slowing the spread, and community mitigation measures to reduce local disease transmission. the application of precautionary and preventive measures in the kingdom of saudi arabia has successfully controlled the spread, reduced the emergence of new cases, and improved recovery rates compared to other regions and countries. in saudi arabia, the ministry of health (moh) has set out specific measures to prevent and mitigate the covid- transmission such as lockdown of cities, restrictions of both domestic and international travel, physical distancing, using protective medical or fabric masks, hand washing, and limits on the size of gatherings. [ ] [ ] [ ] the covid- pandemic is a significant recent global crisis that has had devastating effects on all societies worldwide, leading to a large number of cases and deaths within a short period of time. the major challenges in this pandemic are largely related to matters concerning behaviour and lifestyle of people as well as managing health services to combat disease spread. however, the sustainability of such success requires combined efforts, and the public must be attentive and immediately change attitudes and practices to be aligned with the health authorities' effort. , therefore, this study aims to obtain useful information about knowledge levels, attitudes, and practices (kap) towards covid- in the general population. this was a community-based cross-sectional survey that was conducted from april to may after a full day curfew and lockdown were imposed across the kingdom to combat covid- . this survey aimed to study the knowledge, attitude, and practices of the participants towards covid- preventive and precautionary measures in relation to containment of the pandemic in the kingdom of saudi arabia by determining the participants' socio-demographic characteristics, measuring participants' knowledge about major facts concerning the virus, determining participants' practices to prevent the spread of the infection, and measuring the response rate and participants' level of adherence to moh preventive and precaution measures. all citizens and residents living in saudi arabia who were years of age or older were invited to respond to the online questionnaire, which was distributed through social media (twitter and whatsapp groups). cdc/us epi ifo ver. -statistical (cdc, atlanta, ) was used to calculate the sample size using the total population of million including all residences. the expected frequency was , confidence interval was . %, marginal error was %, and the sample was participants. all provided data were entered to the software which automatically calculated the sample size to be . informed consent for participation was obtained using the interface of the online questionnaire via a statement that informed the respondents that their response assumed that they provided informed consent. to ensure data confidentiality, no personal identifiers were collected. eighty-three questionnaire items were developed by the researchers using google forms. the online questionnaire consisted of four sections and items overall. the first section contained assessed the sociodemographic demographic characteristics of respondents, including gender, age, occupation, marital status, nationality, educational level, and province of residence. the second section consisted of items that assessed the participants' knowledge of covid- . the third section included respondents' attitudes related to covid- . the fourth section focused on participants' practices and behaviour toward covid- . the questionnaire was piloted among participants from the target population to assess the validity of the questionnaire and to ensure that the questions were understandable. the pilot study responses were excluded from the main analysis. the study was approved by the king khalid university research ethics committee. consent for participation was provided by completion and submission of the questionnaire. the data was collected by the developed google form online questionnaire which sent to the public by social media using whatsapp, twitter, facebook. spss ver. was used for data analysis and presentation. for statistical testing, the frequency and percentage were applied while a t-test and one-way anova were used to test for statistical significance, and the percentage was used to test for statistical significance between study variables; p> . was considered to be statistically significant. in addition, the regression tests were used to test the relationship between the knowledge level, attitude, and practice and their relationship to demographic variables. the study included participants who completed the questionnaire. socioeconomic characteristics of the participants are shown in table . over half the population was female ( , %), most respondents ( , . %) were between and years of age, and there were ( %) of participants who were over years of age. most participants ( , %) were of saudi ethnicity and ( . %) of them were married. overall, literacy was a dominant feature, with two-thirds ( , . %) who were graduates and ( . %) who were postgraduates. figure shows the distribution of participants according to administrative regions, as follows: % from mecca, % from the eastern province, % from al-jouf, % from the northern border, % from the riyadh region, % from the qassim region, % from the tabouk region, % from the jazan region, % from the asser region, and % from the najran region. participants' knowledge levels, attitude, and practices regarding covid- are shown in figure . the rate of sound knowl-edge was . % and the rate of a positive attitude was . %, and preventive practices were reported among . % of participants. table presents participants' responses about knowledge on the major epidemiological features of the virus. most (n= ; . %) knew that the respiratory system is targeted most frequently by the virus, and they properly identified the causative agent and symptoms ( . %, . %, respectively). additionally, ( . %) of them knew that the disease is highly contagious, and table shows the participants' attitudes on different issues related to covid- . most (n= ; . %) participants believed that they are susceptible to the infection, while ( . %) showed positive attitudes if any of their family members were infected, ( . %) reported positive attitudes towards isolation in health facility when infection was confirmed, ( . %) believed that hand washing with water and soap for s is significant for preventing transmission, and ( . %) believed that home delivery providers can contribute to the spread of the virus. table shows the practises and/or behaviour of participants towards adherence, compliance, and responses to preventive and precaution measures. the participants' scores were as follows: ( . %) participants properly disposed of the used gloves and tissues, and ( . %) participants recorded safe practices when coughing or sneezing if they were not wearing a mask or using a tissue. compliance with and adherence to staying at home was mentioned by most of the participants ( , . %). the correct responses of participants in dealing with the health messages delivered by moh through the different social media channels were mentioned by ( . %) participants. near two-thirds of the participants ( , . %) reported safe practices in the case of early onset covid- signs and symptoms. more than three-quarters of the participants ( , %) mentioned that they will continue to adhere to preventive health practices after the end of the coronavirus pandemic. table cross-tabulated the demographic independent variables with the mean dependable variables of knowledge, attitude, and practices related to covid- to test their level of association using a % significance level. across age categories, there was a statistically significant difference in knowledge scores (p= . ) and there was no significant difference in attitudes and practices scores (p= . , p= . , respectively). according to nationality, statistics revealed a very strong relationship with knowledge scores (p= . ) and a statistical difference compared with the attitude items (p= . ), although this non-significant correlation was interpreted between this undependable variable and the variables related to practices (p= . ). similarly, a high significance was shown for the occupational status of respondents and knowledge items (p= . ) and a non-significant relationship was shown for attitude and practices (p= . , p= . , respectively). across marital status, there was a strong correlation with knowledge scores (p= . ) and there was no significant difference in attitudes and practices scores (p= . , p= . , respectively). a strong significant difference was found with participants' educational status for all the kap variables (p= . , p= . , p= . , respectively). with respect to gender distribution, there were slight significant differences with knowledge scores (p= . ) and non-significant differences with the attitude and practice variables (p= . ). between regions, knowledge and practice scores were not significantly different (p= . , p= . ), but the significance was strong for attitude (p= . ). table shows the multivariate regression results for knowledge, attitude, and practice-related factors for covid- ; b represents the average change in the dependent vari- the covid- pandemic is a global crisis that has had devastating effects on all countries worldwide, and there have been a huge number of cases and deaths within short period of time. the major challenges related to fighting this pandemic are largely related to matters concerning the behaviour and lifestyle that people have for combatting the disease spread. in the absence of a vaccine and prompt treatment, the public's compliance with preventive measures and legislation is required to contain or reduce the burden of the covid- pandemic. this was found to be strongly linked to people's knowledge, attitudes, and practices. [ ] [ ] [ ] [ ] [ ] [ ] similarly, this study revealed that the general population's knowledge towards covid- improves their attitude, and the attitude level then leads to proper implementation of practice. the present study showed satisfactory knowledge levels towards covid- , and the greater frequency of correct answers regarding knowledge about covid- was almost satisfactory. these findings are consistent with those of other studies that were conducted in the kingdom of saudi arabia. , one study conducted in saudi arabia by al-hanawi et al. reported that the overall accuracy rate for the knowledge test was . %, which is similar to our findings. the findings of this study were also consistent with another study that was conducted by azlan et al. in malaysia, which showed that overall public knowledge was . %. , however, a multinational study that was conducted in the three middle east countries of saudi arabia, kuwait, and jordan and that enrolled , participants revealed that the overall knowledge score among the three countries was . %. the highest score was among jordanians ( . %), while the level of public knowledge in saudi arabia was less than . %; , compared to our study findings, the public level of knowledge in our study was higher ( . %), and this may be attributed to later intense cam- paigns to raise awareness that were launched by the saudi moh through its effective wide-scale communication networks and effective health system. the knowledge level subscales in the current study also showed high scores towards the causative agent and the clinical symptoms of the disease ( . % and . %, respectively). however, only half of the participants knew the correct viral route of transmission. there was only a small percentage of participants who seemed to be unaware of disease complications, and they were only slightly aware of how the virus was transmitted. this is similar to a previous study that was conducted in three countries including saudi arabia, which revealed the lowest public knowledge regarding transmission ( . %). a similar proportion ( . %) had correct knowledge regarding clinical symptoms of the disease, and distinctly poor knowledge ( . %) concerning the possible viral route of transmission was also reported in the same study that was conducted in three countries in the middle east. in our study and a malaysian study, subjects over the age of years had higher knowledge scores, which possibly resulted from a higher risk perception of contracting covid- and complications of the disease. [ ] [ ] [ ] a chinese study also reported surprisingly high covid- knowledge in an epidemiological survey in the early stages of the epidemic, and these authors suggested that it was because the study participants had higher academic degrees, which was similar to our findings. in the present work, respondents were educated from the secondary level to the post graduate level. a study performed to assess knowledge and perceptions about covid- among healthcare workers reported that the awareness varied based on the category of healthcare worker, and there was also insufficient knowledge of participants, but they have a positive attitude. the present study showed satisfactory attitudes towards covid- . this finding was consistent with other previous studies that were conducted in saudi arabia by al-hanawi et al. who reported that the overall attitudes were satisfactory. the present study showed satisfactory positive attitudes in the main matters related to covid- because most ( . %) believed that they were at risk of catching the infection and . % would respond positively to isolation in a health facility if they were diagnosed with or had a suspected or confirmed case of covid- . similar findings were reported by al-hanawi. in another study that enrolled students and staff from alghad private college in jeddah, saudi arabia, more than % of participants exhibited a positive attitude toward covid- . the attitude scores were significantly correlated with some demographic variables including nationality and education level (p= . and p= . , respectively). however, a satisfactory or good level of knowledge related to the virus does not necessarily lead to a high level of positive attitudes that are consistent with participants' knowledge. in contrast to our findings, a study conducted by haque et al. in bangladesh reported that half of the participants had good knowledge, while their attitude and practices towards covid- during the pandemic were not impressive. additionally, the knowledge level does not necessarily end up with a high level of negative attitudes. this was observed in a chinese study in which the level of participants' covid- knowledge was reported to be low compared to a high positive attitude, and the authors attributed this positive attitude to the drastic measures that were implemented by the chinese government to mitigate the spread of the virus. in our study, the participants had a positive attitude towards covid- pandemic prevention and control. the perception of infection susceptibility for a person and their family was higher and preventative measures such as hand-washing were correctly reported by most participants. noticeable positive attitudes were also found in the kap study that was conducted in china. , studies have shown that improved knowledge can affect adverse attitudes and behaviours and thereby suppress the epidemic. , in ethiopia, one study revealed that poor knowledge and misconceptions worsened the conditions during the ebola virus outbreak in . roy et al. observed moderate awareness with adequately informed preventive measures for covid- in the participants. the present study showed that the practices toward covid- were good. this finding was consistent with similar kaps in a covid- study that was conducted in saudi arabia by al-hanawi et al., which reported that the participants' score for practices concerning covid- was . out of (sd . ; range - ); this indicated good practices. theoretically, participants' attitude and practices towards covid- are supposed to be linearly correlated with the education attained. for a study of general kap outcomes ( . %, . %, and . %, respectively), the present study realised this theoretical assumption. the statistical analysis that was performed including linear regression supported this assumption because the relationship between the participants' edu-cational level and their corresponding kaps for covid- as dependent variables were mainly significant (p= . , p= . , p= . , respectively). the highest practice subscales that were reported by the study were covering the nose and mouth while coughing or sneezing, staying at home, and maintaining the advisable social distance. this was interpreted as highly significant with educational levels and non-significant with the other demographic variables. similar observations were reported in the multinational middle east study in which % of participants avoided crowded places and % of participants avoided shaking hands. these findings are similar to the findings of another study conducted by zhong et al. ( ) in china in which . % of participants avoided crowded areas and . % used masks outside their homes during the covid- outbreak. however, this study is not the first study that was conducted in the kingdom, and it is considered to represent ongoing monitoring of the pandemic situation. it shows the progression in the knowledge level, attitude, and practices compared to previous published works, and thus, it provides profile data for later meta-analysis inquires. the improvement in kap levels that was revealed by this study is reflected in the control of the reported daily cases, even after removing lockdown measures within cities and allowing travel between cities. this may have occurred because the population became aware of covid- prevention measures. in addition, the outcomes of this study are promising for sound planning of health education and promotion programs that are targeted toward covid- containment strategies. the limitations of this study include that it is confined to the people using smartphones, e-mail ids and most of the respondents were educated, therefore the responses perhaps not common in all population including uneducated people. the knowledge, attitude, and practice may differ in uneducated people from the findings of our study. another restriction is method of data collection in the critical time amid lockdown, using an online questionnaire may table . regression of knowledge, attitude, and practice related factors to covid- (n= ). results the biased responses. the strengths of this study include that it is conducted during very critical period. the knowledge, attitude, and practice of general public were assessed together. another strength is the sample size of people. however, the study contributes to the literature of a saudi arabia by conducting the in-depth survey of knowledge, awareness practical implementation to overcome the situation. the current study assessed the knowledge, attitude, and practices of the general population, and it showed a satisfactory knowledge level, attitude, and practical implementation of practices to overcome the covid- pandemic in saudi arabia. additionally, demographic variables such as the educational level and age were significantly related to improved knowledge, attitudes, and practices in the population. continuous monitoring of kaps in the general population of saudi arabia improved over time because of the measures taken by government to generate awareness and the strict follow-up of preventive measures to improve the people's understanding of covid- . report : severity of -novel coronavirus (ncov) early evaluation of wuhan city travel restrictions in response to the novel coronavirus outbreak a new coronavirus associated with human respiratory disease in china nowcasting and forecasting the potential domestic and international spread of the -ncov outbreak originating in wuhan, china: a modelling study covid- ): situation reports. wold health organization covid- cases in saudi arabia surpass , . saudi arabia saudi arabia records , new cases as total surpasses saudi arabia confirms new cases saudi arabia's death toll rises to as total cases climb to , . . available from: alarabiya severe outcomes among patients with coronavirus disease (covid- ) -united states a pneumonia outbreak associated with a new coronavirus of probable bat origin epidemiological research priorities for public health control of the ongoing global novel coronavirus ( -ncov) outbreak authority for statistics: the kingdom of saudi arabia . saudi arabia center for disease control and prevention. epi info. atlanta: cdc knowledge and practices towards covid- during its outbreak: a multinational cross-sectional study knowledge, attitude and practice toward covid- among the public in the kingdom of saudi arabia: a cross-sectional study public knowledge, attitudes and practices towards covid- : a cross-sectional study in malaysia public health awareness: knowledge, attitude and behaviour of the general public on health risks during the h n influenza pandemic knowledge, attitudes, impact, and anxiety regarding covid- infection among the public in china knowledge, attitudes and practices towards pandemic influenza among cases, close contacts, and healthcare workers in tropical singapore: a cross-sectional survey knowledge and attitudes of medical staff in chinese psychiatric hospitals regarding covid- fear and stigma: the epidemic within the sars outbreak clinical features and short-term outcomes of patients with corona virus disease in intensive care unit saifuddin: it's a national effort to fight fake news during covid- five more probed for spreading fake news on covid- knowledge, attitudes, and practices towards covid- among chinese residents during the rapid rise period of the covid- outbreak: a quick online cross-sectional survey study of knowledge, attitude, anxiety & perceived mental healthcare need in indian population during covid- pandemic cross-sectional study: knowledge, awareness, and attitude regarding covid- (coronavirus) infection control and prevention among students and staff in alghad college in jeddah knowledge, attitude and practices (kap) towards covid- and assessment of risks of infection by sars-cov- among the bangladeshi population: an online cross sectional survey behavioural change models for infectious disease transmission: a systematic review healthcare professionals' awareness, knowledge, attitudes, perceptions and beliefs about ebola at gondar university hospital, northwest ethiopia: a cross-sectional study contributions: aa, conceptualizing the study, study plan, drafting research tool, data collection; am, fa, provided research methods and instruments, and collected and cleared data; wama, obo, aa, analysed and interpreted data; mh, am, fa, wrote first draft of article; wama, provided technical and advisory support; wama, obo, aa, have critically revised and agreed the final draft of the article and are accountable for the check of similarity. all the authors have read and approved the final version of the manuscript and agreed to be accountable for all aspects of the work. the authors declare that they have no competing interests, and all authors confirm accuracy. we would like to thank king khalid university for support to carry out the study. the authors acknowledge the participants involved in the online questionnaire for their support.ethics approval and consent to participate: the study was approved by the king khalid university research ethics committee. consent for participation was provided by completion and submission of the questionnaire.availability of data and material: available from the corresponding author on reasonable request. funding: no any funding or grant agencies financing or even partially, so the study was fully funded by the authors themselves. key: cord- -z q loy authors: ahmad, naim title: covid- modeling in saudi arabia using the modified susceptible-exposed-infectious-recovered (seir) model date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: z q loy the coronavirus disease (covid- ) pandemic has created unprecedented healthcare emergencies across the globe. the world health organization (who) has proposed social distancing (sd) as a prudent measure to contain the pandemic and, hence, governments have been enacting lockdowns of varied nature. these lockdowns, causing economic and social strain, warrant the development of quantitative models to optimally manage the pandemic. similarly, extensive testing aids in early detection and isolation, hence containing the spread of the pandemic. compartment epidemiology models have been used extensively in modeling such infectious diseases. this paper attempts to utilize the modified susceptible-exposed-infectious-recovered (seir) model incorporating the sd, testing, and infectiousness of exposed and infectious compartments to study the covid- pandemic in saudi arabia. saudi arabia has put restrictions on the movement of people in different phases to ascertain sd. time-dependent parameters based on the timeline of restrictions and testing in saudi arabia have been introduced to capture sd and testing. the arrived model has been validated through statistical tests. the [formula: see text] (r naught), basic reproduction number, value has ranged between . and . with an average of . and currently holds at . . in the absence of sd and testing measures, the model predicts the threshold herd immunity to be . % and [formula: see text] value as . . further, scenario analysis has been conducted for alleviating the sd measure. the results show that early lifting of all restrictions may undo all efforts in the containment of the covid- pandemic. the outcome of results will help policymakers and medical practitioners prepare better to manage the pandemic and lockdown. the current coronavirus disease (covid- ) pandemic has spread from the chinese city of wuhan. it mainly causes the common cold and could cause severe acute respiratory syndrome and may develop into fatal pneumonia [ ] . it transmits from person to person through direct and indirect contact, the fecal-oral route, and respiratory aerosolized droplets [ ] [ ] . it was first reported in wuhan in late december , and the first case in saudi arabia was reported on march , [ ] . as of in saudi arabia, there are a total of , confirmed cases, out of which , people have recovered and , died, leaving , active cases [ ] . the covid- pandemic has created restrictions on the movement of people and everyday activities, which is termed as social distancing (sd). as the world health organization (who) endorses physical distancing, wearing masks, washing hands with soap, and cleaning hands with alcohol-based hand rubs as some of the solutions to contain the pandemic until an effective drug or vaccine is available. this has resulted in lockdowns and severe strains on the economic activities and the mental and psychological well-being of many. therefore, to strike a balance between healthcare and economy, decision-makers need a quantitative model to predict the pandemic in order to ease lockdowns, resume economic activities, and protect the mental and psychological well-being of people. compartment epidemiology models have been widely used to quantify the trends of such infectious diseases. this study aims at using such a compartment epidemiology model to analyze the dynamics of the covid- epidemic in saudi arabia. the base compartment epidemiology model is susceptible-infectious-recovered (sir) [ ] and the extension of it is susceptible-exposed-infectious-recovered (seir). to study the dynamics of the covid- epidemic, several modified seir models have been used to incorporate various measures, especially social distancing, testing, public responses, and mobility restrictions [ , [ ] [ ] [ ] [ ] . the modified models have a large number of parameters that increase the complexity. incorporation of social distancing is essential and hubbs [ ] has used a single parameter to incorporate sd. further, as the measure of social distancing varies with time, hence, de falco et al. have introduced dynamic sd [ ] . dur-e-ahmad et al. [ ] incorporate the infectiousness among the exposed compartment similar to that of the infectious compartment as identified by he et al. [ ] . and berger et al. have modified the model with a testing parameter [ ] . the objective of this paper is to model the covid- pandemic in saudi arabia using seir, including sd, testing, and the infectiousness of exposed and infectious populations. for the simulation of the mathematical model, the python language has been used and results are validated with statistical analysis. further, the scenario analysis has been done to calculate threshold herd immunity and to study the effects of the alleviation of restrictions. the compartment epidemiology model seir divides the population of study into four compartments: susceptible , exposed , infectious , and recovered . the susceptible compartment represents a population that is prone to covid- , whereas the exposed population has acquired coronavirus but is asymptomatic. an infectious population has symptoms of coronavirus such as fever, cough, and fatigue and may infect the susceptible population. finally, the recovered compartment represents individuals that have either recovered or died. mathematically different compartments are governed by following differential equations ( ) ( ) ( ) ( ) . it is assumed that the total population ( ) remains fixed and recovered individuals remain immune to the disease during the study period. the parameter represents the average contact rate and and represent the inverse of the central measures of incubation period and infectious period. there is also one important index r naught, , known as the basic reproduction number that signifies the number of susceptible individuals that will get infected by an infectious individual. the value of needs to be less than one for a pandemic to die out. in the seir with sd model, one more parameter is introduced to represent sd that varies between (ideal isolation) and (no sd) [ ] . and in a dynamic sd case, the value of will vary with time based on the sd measure variations [ ] . similarly, dur-e-ahmad et al. have incorporated and to represent the relative infectiousness of exposed and infectious compartments, respectively [ ] . further, there are studies that have added parameter to represent testing [ ] . hence, a composite parameter to represent net measures is computed as , and mathematically, the positive part of this parameter ( ) is used, meaning for negative values, it will be zero. therefore, the mathematical formulation of the modified seir model adopted for the current study changes equations ( , ) as follows, whereas the equations ( , ) remain the same. the basic reproduction number ( ) is "defined as the expected number of secondary cases produced by a single (typical) infection in a completely susceptible population" [ ] . a nextgeneration matrix may be used to drive the equation of [ ] . using equations ( , ) , new functions and may be defined to represent the rate of new infections and the rate of transfer in and out of exposed and infectious compartments. therefore, the matrices and are defined, as shown in equations ( , ) . and the next generation matrix is defined as . the largest eigenvalue of (the spectral radius) gives , as given in equation ( ). there are a total of seven parameters , , , , , , and , and one derived parameter . and are disease-specific and calculated with incubation and infectious periods. signifies the contact rate and is modified by and accounting for social distancing and testing, respectively, or by net measures . and are modification parameters for the relative infectiousness of exposed and infectious populations. the incubation period ( ): the time period during which the exposed people become infectious and symptomatic is called the incubation period. the incubation period ranges between two and days [ ] . generally, the mid-value of days of the incubation period is considered but in the case of saudi arabia, the median incubation period is identified as six days [ ] . the inverse of the incubation period is known as the incubation rate. infectious period ( ): the time period during which an individual remains infectious and thereafter recovers or dies. this period is given between zero to days [ ] , three days or seven days [ ] , and . days [ ] . the inverse of the infectious period is known as the recovery rate. the value of this parameter has been taken within the acceptable range and in conjunction with model fitting in simulation. net measures ( ): the net measures ( ) is mathematically the positive part of the difference of social distancing ( ) and testing ( ). the social distancing ( ) measures are implemented differently by countries and vary with time. saudi arabia firstly suspended overseas umrah visitors on february , [ ] . the first case of covid- was detected on march , [ ] . thereafter, restrictions of a different nature were implemented such as curfews, classroom learning at schools and institutions, closure of private and public sectors, inter-city movements, hot-spot isolation, suspension of sports events, restrictions on public gatherings, prayers in masjids, suspension of domestic air and road transport, and others. the intensity of these measures was at the peak during march - , , for the eid festival by a hours nationwide curfew. after this relaxation period started in three phases, may - , , may -june , , and june , , onward. during the first phase, curfew was relaxed between am and pm, in the second phase, it was extended to pm, and in the third phase, it was relaxed completely. and all of the economic activities have been allowed with precautionary measures, such as face masks, sanitization, and physical distancing. but, still, international flights, overseas umrah, and school and colleges are closed and precautionary measures are being observed. based on these measures, a time-varying sd parameter has been defined, as shown in figure . the testing data for saudi arabia has been taken from the saudi ministry of health [ ] and the oxford covid- government response tracker [ ] and indexed between and to compute (figure ). both and values have been chosen to represent the sd restrictions and testing data in conjunction with model fitting in simulation. techniques [ ] . the value of is higher than the value of . the value of contact ratio ( ) is also estimated through optimizations techniques [ ] . the value of has been taken near and the values of and have been derived through simulation and optimization techniques. the model represented by ordinary differential equations ( , , , ) is utilized for the simulation of the pandemic in saudi arabia. coding was done in the python language [ ] in the environment of jupyter notebook [ ] . the equations were solved with the help of the function solve_ivp from the scipy.integrate sub-package. further, the minimize function from the scipy.optimize sub-package was used to minimize the difference between predicted and reported values of total cases to estimate and . the values of other parameters were given as defined previously such as . for the values of and , discrete events of sd and testing data were smoothed out slightly using the univariatespline function with a smoothing factor of . (figure ) . thereafter, the values of were computed from the smoothed values of and . the initial values for solving the ordinary differential equations were as follows (cases on first day), (assumed that five times individuals are exposed on first day), (recovered on first day) and , as the total population of saudi arabia is , , . the levene statistical tests were performed to validate model results against the epidemic reported data from the saudi ministry of health [ ] . the resultant model identified the values of and to be . and . by fitting the values of cumulative total cases against the reported cumulative total cases up to august , ( figure ) . the levene test (statistic= . , p-value= . ) shows that there is no significant difference between model values and reported values. further, in figure , it is evident that the model is fitting closely with the cumulative recovered cases as well. as the levene test (statistic= . , p-value= . ) confirms that there is no significant difference between model values and reported values. similarly, the cumulative active cases that include exposed and infectious populations fit closely and the levene test (statistic= . , p-value= . ) proves the same. the results of the simulation show a very significant model fitting, as all the three publicly reported data, such as total cases, recovered cases, and active cases, show no significant difference from the respective model values. the model results in the current scenario of restrictions and testings depict that there are multiple peaks for active cases (figure ) . it identifies two visible peaks in the period of days of neighborhood data settings to identify the local maxima. this pattern also closely resembles the reported data although the absolute values differ with the reported data within statistical non-significant limits. the value has ranged between . and . , with an average of . , and currently holds at . . as the current value of is less than one, the pandemic is expected to decline and the peak has already passed ( figure ). it is important to achieve herd immunity for the pandemic to decline in the absence of any measures. as of now, there is no proven vaccine for covid- , therefore, herd immunity can only be achieved when a substantial proportion of the population has recovered with the assumption that the recovered become immune to covid- . therefore, this scenario removes the sd and testing measures and recomputes the model results with the parameter values identified in the fitted model previously. the value has come out to be . and threshold herd immunity ( ) will be achieved at . % of the population ( figure ) . further, the pandemic will infect . % of the population by the end. further, the sd measures were varied for two possibilities and compared with the current measures (low-risk scenario). the first possibility is gradual full normalization by december , , and termed as a high-risk scenario. and the second possibility could be gradual partial normalization by june , , the expected date of vaccine (medium-risk scenario), whereas covid- testing is assumed to continue at the same level. the values of and for the above-mentioned three scenarios are shown in figure . the peak total active cases are , , , , and , , for low-risk, medium-risk, and high-risk scenarios, respectively ( figure ). these peak values are supposed to be achieved on the th day (july , ), th day (july , ), and th day (december , ) for the respective scenarios. in the low-risk scenario, the peak has already passed at a relatively very low value of , for active cases, the current scenario. in the second scenario of mediumrisk, the peak is flattened and delayed beyond the arrival of the expected vaccine date, although the peak value is almost . million of active cases, which is a huge number to be managed. the third scenario of high risk will bring a very high peak value of almost . million active cases before the end of this year and way before the expected vaccine date. this study has modeled the covid- pandemic using a modified version of the base compartment epidemiology model of seir. the modification was achieved by the introduction of four parameters accounting for the social distancing, testing, and infectiousness of exposed and infectious populations. the mathematical equations corresponding to the modified model were simulated in a python environment. the optimization technique was used to fit the model with reported cases by the varying contact rate and infectiousness of the exposed population. the remaining model parameters were chosen within the acceptable range and in conjunction with model fitting. the statistical analysis shows a good model fit, as the model results for total cases, recovered cases, and active cases have no significant difference with those of reported cases. as per model results, the peak has already passed and the pandemic is expected to decline with current measures in place. hence, the current measures have been proven to be very effective in saudi arabia. the model has been run on different scenarios for social distancing to predict the possible outcomes. the results indicate that early complete normalization efforts may undo the successful containment of the pandemic. therefore, the decision to alleviate restrictions has to be well worked with other mechanisms such as increasing the testing capacity and throughput and the availability of effective drugs and vaccines. nonetheless, due to unavoidable assumptions and the exponential nature of functions for all categories of cases, actual numbers may vary from the model results and care should be taken in interpreting the results. human subjects: all authors have confirmed that this study did not involve human participants or tissue. animal subjects: all authors have confirmed that this study did not involve animal subjects or tissue. conflicts of interest: in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. preparedness and response to covid- in saudi arabia: building on mers experience dynamics of sars-cov- outbreak in the kingdom of saudi arabia: a predictive model fecal transmission in covid- : a potential shedding route protection from covid- a contribution to the mathematical theory of epidemics transmission dynamics of the covid- outbreak and effectiveness of government interventions: a data-driven analysis an seir infectious disease model with testing and conditional quarantine outbreak dynamics of covid- in europe and the effect of travel restrictions transmission dynamics model of coronavirus covid- for the outbreak in most affected countries of the world coronavirus covid- spreading in italy: optimizing an epidemiological model with dynamic social distancing through differential evolution temporal dynamics in viral shedding and transmissibility of covid- notes on r perspectives on the basic reproductive ratio incubation period of novel coronavirus ( -ncov) infections among travellers from wuhan, china clinical characteristics of covid- in saudi arabia: a national retrospective study on a statistical transmission model in analysis of the early phase of covid- outbreak the effect of control strategies to reduce social mixing on outcomes of the covid- epidemic in wuhan, china: a modelling study seir and regression model based covid- outbreak predictions in india oxford covid- government response tracker the python language reference manual jupyter notebooks-a publishing format for reproducible computational workflows. positioning and power in academic publishing: players, agents and agendas. loizides f, schmidt b the author is thankful to king khalid university for all the support. key: cord- -jkzbyqtm authors: alqurshi, abdulmalik title: investigating the impact of covid- lockdown on pharmaceutical education in saudi arabia – a call for a remote teaching contingency strategy date: - - journal: saudi pharm j doi: . /j.jsps. . . sha: doc_id: cord_uid: jkzbyqtm background: covid- lockdown has forced pharmacy education to be conducted remotely for approximately half of the second semester in the year / . this sudden shift to distance learning has put the pharmacy education system through an extraordinary experience that may impact its future. objective: to investigate the effect emergency remote teaching has had on pharmacy education in saudi arabia, and to provide recommendations that may help set in place a contingency strategy. methods: two cross-sectional likert-scale based questionnaires targeted at students and teachers separately, designed to explore stakeholders' satisfaction in three areas of emergency distance teaching/learning: the use of virtual classrooms, completion of course learning outcomes (clos) and assessment via alternative methods during the covid- lockdown period. furthermore, phone interviews were conducted with teachers and students to discuss results from both questionnaires for further clarity on teacher and student views. results: over pharmacy students, from different local colleges, and faculty members from different local colleges have participated in this study. while it was challenging for the majority of teachers (> %) to delivery complex scientific concepts over virtual classrooms, > % of students and % of teachers have expressed concerns on the lack of student–student and student–teacher interactions. a factor that has shown a significantly negative correlation with student overall satisfaction (p < . ). emergency remote teaching has forced teachers to alternative assessment methods, which the majority ( %) believe had a positive effect on students' overall skills. almost half of students ( %) were concerned by the lack of guidance accompanied by unfamiliar methods of assessments. conclusions: based on statistically analysed results from cross sectional likert-scale questionnaires aimed at stakeholders of pharmaceutical education, this study concludes with a number of recommendations that may help pharmacy colleges seize this unique opportunity to further enhance the quality of pharmacy education in saudi arabia. prior to , the college of pharmacy at king saud university was the only college that offered an undergraduate pharmacy related degree program in saudi arabia (alhamoudi and alnattah, ) . since then, a sharp increase was observed in the number of pharmacy colleges (alhamoudi and alnattah, ) . according to a report published by the saudi commission for health specialities (scfhs, ) the number of pharmacy colleges in saudi arabia has reached in hosting over , students (scfhs, ) . this came as a result of a government funded and managed mission of advancing higher education in the country to meet national demands in various sectors, such as healthcare and the pharmaceutical industry (alhamoudi and alnattah, ) . while pharmaceutical education in saudi arabia is relatively young, compared to that of other countries such as the uk and the usa, it has witnessed a significant growth and development in its quality, due to the continuous revision and standardization process encouraged by various boards and councils (asiri, ) such as the national centre for academic accreditation and evaluation (previously known as ncaaa). furthermore, experts in the field in saudi arabia, have recently started to publish their experiences in developing pharmaceutical education as part of acquiring national and international accreditations (alkatheri et al., ) . according to the accreditation council for pharmacy education (acpe), so far, four doctor of pharmacy (pharm d) programs offered in saudi arabian institutions have been accredited internationally (acpe, ) . the challenge all educators in saudi arabian institutions and around the world are currently tackling is the sudden shift to distance learning enforced as a measure to prevent the spread of covid- . from the th of march the saudi arabian ministry of education has directed all schools, colleges, and universities in the country to indefinitely suspend student attendance, and to activate distance learning as an alternative. henceforth, teaching was carried out remotely and replaced by virtual classrooms. this was possible via online learning management systems such as blackboard and microsoft teams. universities around the country spent great efforts launching a variety of online training sessions and providing basic manuals to equip academics for online teaching. this all started taking place after weeks into the second term, where a minimum of weeks of teaching remained. as directed by the minister of education and university presidents, program management teams across all universities in saudi arabia have held emergency meetings to handle this sudden change of teaching strategy. the common goal was to ensure quality of teaching is maintained by assessing all course learning outcomes (clos) and using appropriate methods that account for the limitations of remote teaching. furthermore, to ensure student satisfaction, the ministry of education, through university admissions, has directed all program management teams to modify the distribution of assessments, assigning % of the total course mark to coursework related activities, with the remaining % allocated to final assessments. lecturers were given a wide range of evaluation methods to choose from. for coursework related activities, examples include reports, essays and student presentations. the final assessment included oral examinations, open book examinations, and online multiple-choice questions. although most pharmacy program management teams did not have a contingency plan in place for such circumstances, with the guidance of the ministry of education and university managerial teams, the teaching and assessment periods of the second term in the academic year / were successfully completed. whilst measuring the level of success for this accomplishment may be possible through established program key performance indicators, this study investigates the effects these extraordinary circumstances have had on pharmacy education. here the author acquires both student and teacher feedbacks on the experience, its difficulties and successes. this study aims to help in forming a basis for developing a contingency strategy for emergency remote teaching in the field of pharmaceutical education in saudi arabian universities. a cross sectional pharmacy student-targeted online questionnaire was developed using google forms. in attempts to ensure only pharmacy students' response, an opening question of the program name was used to filter out non-pharmacy students. followed by a few demographical questions as well as determining the institution's name and program year in which the participant is currently in. the questionnaire was designed to measure students' satisfaction, using point likert-scale questions (joshi et al., ) , in three different areas: virtual classrooms, completion of course learning outcome (clos) and alternative assessments. the experience of graduating students was also explored via questions on pre-registrational training during the lockdown phase. in each area, the questionnaire was designed to identify major challenges and obstacles students have faced during the distance learning. furthermore, participants were provided with an ending segment to add any relevant comments. as part of the development process, the questionnaire was revised and amended post pilot testing on a group of volunteer students. a second teacher-targeted cross-sectional questionnaire was developed to measure their satisfaction in the same three areas of interest. to avoid participations from academics in all areas, the questionnaire was adapted with an opening filtering question considering only faculty members that have participated in teaching and assessing pharmacy students, in saudi arabian institutions, during the lockdown. the questionnaire included ending segments to allow teachers to further add any comments or suggestions they see fit. the questionnaire was put through a pilot test by a group of volunteer academics to revise and amend. the study was reviewed and approved by the ethics committee of taibah university. using the electronic platform ''google forms" both questionnaires were sent to different institutions in saudi arabia. the teacher-targeted questionnaire was directed to pharmacy program managerial teams for distribution amongst faculty members, whilst the student-targeted questionnaire was directed to student group leaders to distribute amongst pharmacy students from all program years. both questionnaires were conducted during may . awarded student marks, from the past three years, in four randomly selected courses in different areas of pharmaceutical sciences, were collected from consenting volunteer faculty members. student names and id numbers where erased to protect their privacy. to further clarify the students' and teachers' voices and comments from open-ended questions, individual interviews were conducted remotely with three students and four teachers from the college of pharmacy in taibah university. in the interviews, results from both questionnaires were discussed with all participants. conclusions were drawn, recorded, and used in both the results and discussion parts of this study. diverging stacked bar charts were used to help present results from likert-scale questions in both questionnaires. awarded marks as well as student satisfaction scores were presented using a box plot. coefficient analysis between students' satisfaction and variables of likert-scale ordinal output data, was conducted using non-parametric spearman's rank correlation on ibm Ò spss statistics software. responses from the student-targeted questionnaire included students from different saudi arabian colleges, covering most saudi arabian regions, % of which were from taibah university (table ) . this included students from all levels and stages of undergraduate programs, pharm d and bachelor of pharmacy (b pharm), including the pre-registrational training year (table ) . student sample size represents approximately % of the population, as the total number of undergraduate pharmacy students in saudi arabia is estimated at , (scfhs, ). the teacher-targeted questionnaire on the other hand, yielded only academics from different colleges (table ) . assuming a student to teacher ratio of to , as stated by the ministry of education to be the average student to teacher ratio in saudi arabian colleges (moe, ) , the author estimates the total number of members in pharmacy faculties to be , therefore the teacher based sample in this study represents an estimated % of their population. although a higher percentage of teachers than students have participated, the number of colleges represented in the teacher-targeted questionnaire output is much lower. this may indicate that teachers were occupied with post-teaching activities such as the submission of course portfolios. additionally, the author has noticed many circulated research-based questionnaires investigating varies aspects in relation to covid- , this may have lowered participation interest in general. results from the -point likert-scale questionnaires were presented using diverging stacked bar charts in figs. and for students and teachers, respectively. participants with neutral responses were positioned at the centre of the horizontal axis. agreeing and disagreeing participants where positioned on the right and left sides of the horizontal axis, respectively. responses to various statements were grouped under main categories: virtual classrooms, course learning outcomes (clos), alternative assessment methods (fig. & ) and training via alternative activities ( fig. only) . individual interviews were conducted remotely with three students and four teachers all from the college of pharmacy at taibah university. these interviews included a discussion on questionnaires output, specifically comments and ideas posted by participants in open-ended questions. results from interviews has been incorporated into the following sections. results show > % of students and > % of teachers reported difficulties with internet connection, and thus attending and maintaining presence in virtual classrooms (fig. & ). while attendance may be an issue for some, most teachers (> %) agree that it was difficult to use distance learning tools in delivering complex scientific concepts (fig. ) . student-teacher interactions were reported to be limited, by > % of students and almost % of teacher participants, causing difficulties for students to understand lecture content (fig. & ). interviews with some of the student representatives have also revealed that, in virtual classrooms, student-student interactions have also been limited, thereby limiting peer collaborations which otherwise many students depend on in normal circumstances. approximately % of students agree that it was more difficult to concentrate during virtual classrooms, rendering them less effective ( fig. ) . furthermore, student representatives in an interview have explained that although a student maybe signed into a virtual classroom, they may be distracted by other applications especially if they are attending via their smart phones. while very few teachers have reported previous experience with virtual classrooms, for the majority, this was their first attempt of being on the teaching side ( fig. ). learning how to use new tools and coping with the pressures of distance teaching has split teacher opinion on whether such tools are appropriate for pharmacy related subjects (fig. ). due to not being able to attend laboratories, psychomotor based clos were not completed. in addition, approximately % of teachers have admitted to not being able to completely cover clos (fig. ) . > % of students believe they have gained limited knowledge and skills, similarly, almost % of teachers believe that students have not gained all essential knowledge and skills during the lockdown period (fig. & ). > % of students and % of teachers have shown interest in the idea of conducting revision sessions for essential course learning outcomes next semester (fig. & ) . table demographic details of participants in both questionnaires (n = ). data collection was completed through google forms. as the links to the teacher-based questionnaire and student-based questionnaire were sent directly to program management teams and student leaders respectively. out of the targeted pharmacy colleges in the country, students from different institutions and academics from different institutions have responded. student sample is representative of the population in terms of gender, program title and year of program. the academics sample includes all teaching positions. no. of participants (%) gender while the most common conventional method of assessment may be written examinations, the lockdown period has necessitated alternative remote methods. in addition to online multiplechoice question (mcq) exams, teachers have resorted more to assessment via written assignments and online oral examinations. this new experience has alerted teachers to the benefits of these alternatives, as % believe they can enhance student overall skills (fig. ). this has prompted the majority of teachers (> %) to consider a reduction in the number of exams while increasing alternative methods of assessment for courses in the future (fig. ) . while teachers were split on the practicality of online examinations, most students did not favour written assignments and oral examinations (fig. & ). student representatives in interviews explained that many students had limited experience in writing essays and or reports, therefore undergoing such assessment required a substantial effort, especially when a plagiarism check is required. furthermore, they explain that oral exams were very difficult to prepare for, as the scope of the exam can be very wide. in many cases students were not presented with what to expect in an oral exam, thus preparations and revision were less effective. a lower proportion (< %) of students were unfavourable to assessment by online seminar presentations, while some may have struggled due to poor internet connections (fig. ) . student representatives attribute this response to the limited experience students have in giving presentations in general. students have also shown concern towards the high number of assignments given during this lockdown. student representatives explained in interviews that a sudden influx of assignments was pushed in a very limited period. a student representative stated the following in an interview: ''we believe that each teacher was unaware of the assignments given to us by his colleagues". suggesting they wanted some informed knowledge, as assurance, on college oversight of academic staff in terms of managing the total number of assignments. approximately % of students claimed to face difficulties in understanding the requirements of some assessment methods (fig. ) . furthermore, several student interview participants have claimed that the evaluation criteria for some assessments were unclear, which they believe caused some of the marking processes to be susceptible to subjectivity. others have commented that not fully understanding the reasons behind loss of marks has caused students distress and the feeling of unfairness. when students were asked whether assessments performed during lockdown were fair and proportionate, almost % answered ''no" (data not presented). however, when comparing student marks for the past three years (fig. ) the cohorts assessed during covid- fig. . diverging stacked bar chart to show results from a -point likert-scale student-targeted questionnaire to measure student level of agreement with several statements in categories concerned with the educational process during covid- lockdown, these included: virtual classrooms, completion of clos and alternative assessment methods (n = ). graduates were also asked to participate with their feedback on training via alternative activities (n = ). full statements from the questionnaire were abbreviated above due to limited spacing. full statements are as follows: (s ) i struggle with attending virtual classrooms due to internet connection problems; (s ) with remote teaching i have had limited interactions with teachers causing difficulties in understanding the lecture materials; (s ) virtual classrooms are ineffective as one can easily be distracted; (s ) during covid- lockdown i was unable to absorb all knowledge and skills associated with this term and as a result i fear it will affect my performance as a pharmacist in the future; (s ) number of assignments requested during the covid- lockdown were very high with limited time for completion; (s ) witten assignments such as essays and reports were not suitable for this duration as they're very time consuming and require a lot of effort; (s ) oral exams were a suitable alternative to written exams as they allow demonstration of knowledge and skills with ease; (s ) online seminar presentations are suitable alternative methods of assessment; (s ) i had difficulty understanding the required actions for the assessment methods used during the lockdown; (s ) completing training program requirements with alternative activities will negatively impacts my future professional performance; (s ) completing training program requirements with alternative activities will reduce my chance of obtaining a job. lockdown appear to have gained significantly higher marks in all courses (p < . ). marks awarded during lockdown were densely populated in the upper part of the grading scale ( % - %), thus indicating less discrimination between student marks and perhaps some inaccuracy in measurement of clos (fig. ) . this comes in agreement with teachers' responses as a majority (> %) believe that assessments this semester were less accurate in measuring student attainment of clos, and therefore do not entirely reflect students' knowledge and skills (fig. ) . both pharmacy programs, b pharm and pharm d, include a training period that involves working in hospitals, community pharmacies and pharmaceutical industrial facilities. results from the student-based questionnaire indicate that, because of the lockdown, most trainees ( . %) (data not presented) were asked to stop attending training locations and instead were assigned alternative activities and assessments that mimic training programmes. while most students do not believe it will have a significant effect on their performance as future pharmacists, at least % of trainees believe that it may reduce their chances of employment in the foreseeable future (fig. ) . using a -point scoring system, with being the lowest part of the scale, students were asked to express their level of satisfaction with the performance of their college in managing educational processes during the lockdown period (fig. ) . results show colleges (abbreviated with letters b, c, d, h, j, k, n, p and r) with majority responses ranging from to , thus indicating a fairly good student satisfaction. six colleges (abbreviated with letters a, e, g, l, m and o) seem to range between satisfied and unsatisfied students. out of the colleges, only (abbreviated with letters f, i and q) seem to include some very unsatisfied students. responses for some of the colleges included a very wide range ( - ) such as the college abbreviated with the letter q. this may indicate inconsistency in management performance, while colleges with a score range of points or less may have been consistent with their performance. results from a coefficient analysis of non-parametric spearman's rank correlation (table ) indicate that major factors negatively influencing student satisfaction include limited student -teacher interaction and perceived ambiguity in assignment instructions (p < . ). although unrelated to university performance, statistical analysis shows internet connection problems as well as difficulty with concentrating in virtual classrooms, has lowered student satisfaction to some degree (p < . ) ( table ) . diverging stacked bar chart to show results from a -point likert-scale teacher-targeted questionnaire to measure teachers' level of agreement with several statements in main categories concerned with the educational process during covid- lockdown, these included: virtual classrooms, course learning outcomes (clos) and alternative assessment methods (n = ). full statements from the questionnaire were abbreviated above due to limited spacing. full statements are as follows: (s ) prior to the covid- quarantine phase, i had very little experience in using virtual classrooms; (s ) after using virtual classrooms this semester, i believe it to be an appropriate teaching tool for most pharmacy related courses; (s ) i struggle with internet connection and thus find it difficult to stay connected to a virtual classroom; (s ) explaining complex scientific concepts to students through virtual classrooms is difficult and requires more time than conventional teaching; (s ) interacting with students in virtual classrooms to ensure they have understood certain concepts is difficult to achieve; (s ) during this phase, i believe i was able to cover all learning outcomes, except for psychomotor ones; (s ) most students have gained all required knowledge and skills; their performance as pharmacists in the future will not be negatively affected by the covid- quarantine phase; (s ) distance learning tools, such as the blackboard, are impractical & ineffective for exam assessments; (s ) due to covid- quarantine, it was very difficult to assess students' abilities and performance with regards to course learning outcomes; (s ) awarded grades this semester are not an accurate reflection of students' knowledge and skills; (s ) prior to covid- , assessment methods were mainly limited to mcq based exams; (s ) mcq exams are less accurate in the assessment of student skills; (s ) introducing students to a wide range of alternative methods of assessments this semester will have a positive impact on their overall skills; (s ) i recommend that methods of assessment, stated in course specifications, are changed to include less exams and more assignments. the covid- pandemic has forced college academics across the world to remotely teach and assess students in all levels and fields of higher education institutions. the ministry of education in saud arabia has supervised the transition across the country and contributed to its efficiency. the presence of a strong infrastructure for distance learning such as internet connectivity, subscriptions to various e-systems and the readiness of experts in every institution has made it possible to continue teaching during the lockdown period. many faculty members in health care education had limited experience with distance learning tools, however, administrative teams made a swift and extraordinary effort to train all on the basic use of software such as creating virtual classrooms and online exams on blackboard and microsoft teams. although the efforts were outstanding, faculty members were short for time, as many were split between learning how to operate new technologies and teaching. results from this study indicate that pharmacy faculty members have gained considerable experience in the basic use of distance learning tools, yet there remain many features that can enhance that experience and perhaps help teachers and students overcome some of the observed challenges. both teachers and students have identified the lack of human interactions to influence their ability to remotely teach and learn, respectively. statistical analysis has shown that the lack of interaction has been a significantly negative factor in student satisfaction. research in education has proposed that interactions between students themselves and between students and teachers is fundamental for effective distance learning (moore, ; hunter, deziel-evans, and marsh, ) . furthermore, contemporary education values student-student interactions considerably, as learning can be enhanced when students share their findings with each other (hunter, deziel-evans, and marsh, ) . embedding interpersonal skills in health education has also been known to help prepare caring, competent practitioners (bischoff et al., ) . this challenge may be overcome by utilizing available features in distance learning e-systems, such as discussion forums, to help boost student-teacher and student-student interactivity. this in turn may help students engage and focus better in virtual classrooms, an issue many students have faced during the lockdown. adopting collaborative teaching and learning strategies can encourage group-learning and prevent learning in an isolated environment. unlike traditional teaching, remote teaching has the advantage of technology incorporation, where various teaching strategies may easily be implemented. one of which is the ''flipped classroom", where lectures may be pre-recorded and posted for students to watch at their convenience (mclaughlin et al., ) . in place of virtual classrooms, a virtual discussion room can be utilized to accommodate students' collaborative efforts in learning. problem-based learning (pbl), amongst student-centred teaching strategies, is another example for a suitable method to use in distance learning. not only would it encourage exchanges, but it can also propel students to be independent learners as opposed to memorizing information of traditional lecture formats (cyr, ; camp, ) . published studies further showed students taught using the pbl strategy to be motivated and self-directed life-long learners, essential characters for pharmacist practitioners (hunter, deziel-evans, and marsh, ) . (mcgill, tukey, and larsen ) comparing marks of randomly chosen courses, with different pharmaceutical fields, over a period of three years (i.e. cohorts of students). awarded marks in represents assessment during the covid- lockdown. the horizontal borders of each box represent the st and rd quartiles of student scores (wickham and stryjewski, ; mcgill, tukey, and larsen, ) . upper and lower whiskers represent the highest and lowest awarded marks for each cohort respectively (wickham and stryjewski, ; mcgill, tukey, and larsen, ) . the mean ± std (n > ) values are pinned to each group. outliers were identified using the interquartile range (iqr) rule (schwertman, owens, and adnan ) . mean and median values are relatively close, thus indicating normal distribution (krzywinski and altman, ) . using an unpaired two-tailed unequal variance t-test (kim, ) , the student marks, for all courses, were found to be significantly different from the and cohorts (p < . ). a comparison between the and cohorts shows no significant difference in courses a and c (p < . ). the most challenging part of conducting distance education during the lockdown has been the remote assessment. although many distance learning systems provide platforms for online exams, teachers have a negative perception as students are not under monitoring and thus may be able to cheat (kaczmarczyk, ) . furthermore, the use of distance learning tools for online exams required learning more about the formatting needed, which can be complex. many teachers have resorted to alternative assessment methods, this included written assignments, where students were asked to write a report or an essay through which a demonstration of attaining a learning outcome is measured. results from this study, however, shows that many students had difficulties understanding the required action. while in many cases, written instructions where provided to students, the lack of experience in dealing with such assignments has left students frustrated. to add to this, the concept of plagiarism is new to many, as a result, students have struggled to write in their own words. results from this study also show that perceived ambiguity in assignment instructions has been one of the significant factors in influencing student satisfaction (p < . ). interviews with students and teachers have revealed the feeling of unfairness many students share. despite this, analysis of student grades, during the lockdown, has revealed a significant increase when compared to the past two years. although only four courses were investigated, this was further confirmed by all interviewed academics. regardless of struggles, the majority of teachers believe that alternative assessment methods will have a positive impact on students' overall skills. thus, many support changing plans of assessment methods, stated in course specifications, for post-lockdown teaching. while exams are an excellent tool of a summative assessment, these alternates may be more suited for ongoing formative assessments. traditionally, a greater percentage of the total course mark is dedicated to exams and only a small fraction (% %) is reserved to alternative assessments. while this may reduce the workload on academics, and especially if exams are of mcq nature, student attainment of various clos based skills are not accurately measured. this includes cognitive, interpersonal, timemanagement, communication, and information technology skills. in many cases, such skills contribute to half the clos while only % of the course marks were conventionally used to assess them under the ambiguous category of ''activity". this has indirectly guided students to focus on memorizing lecture materials and ignore other sources of information. fig. . box plot (mcgill, tukey, and larsen, ) to demonstrate and compare students satisfaction, on a point scoring system, with the performance of their colleges in managing educational processes, during the covid- lockdown period, grouped by institution. names of institutions were anonymously substituted for a letter to protect their privacy. the horizontal borders of each box represent the st and rd quartiles of student scores (wickham and stryjewski, ; mcgill, tukey, and larsen, ) . upper and lower whiskers represent the highest and lowest values scored by each group of students, respectively (wickham and stryjewski, ; mcgill, tukey, and larsen, ) . the mean ± std (n ! ) values are pinned to each group. outliers were identified using the interquartile range (iqr) rule (schwertman, owens, and adnan, ) . for both groups, b and r, student satisfaction values were densely populated on scores and , respectively, causing the highest and lowest scores along with the st and rd quartiles to be of the same value, therefore reducing the box and whiskers to a single line. student groups with< respondents were excluded (n = ). results of a correlation analysis, using non-parametric spearman's rank coefficient, between student satisfaction with the college performance in managing educational processes during the covid- lockdown period, and responses to questions from fig. . spearman's rank correlation coefficient was used in this instance as the output of likert-scale questionnaire is of ordinal data. (n = ). correlation with student satisfaction while exams may be used to assess knowledge and cognitive skills, the process of building ones knowledge through research, interpretation, analysis and evaluation followed by sharing his or her findings through a concise well-written document or an engaging presentation, can stimulate critical thinking and collaborative learning. where teachers can not only act as information providers but also help as modulators and facilitators. integrating alternative methods of assessment and collaborative student-centred teaching strategies may be the responsibility of teachers and program management teams. pharmacy students must also be encouraged to adopt a proactive learning strategy, where complete dependence on teachers for information is discouraged. although some students may have unrealistic expectations of the need to be ''spoon-fed" information and be awarded full marks simply by regurgitating the information back in an exam, it is the teacher's responsibility to push students towards taking responsibility for their own learning. an emphasis should be placed on testing the depth of student comprehension of critical clos. teaching remotely during the lockdown period was an excellent opportunity to revise teaching strategies and assessment methods used in normal circumstances. this study does not only encourage a contingency plan for emergency remote teaching, but also for a change in the everyday educational process that can positively impact teacher and student performance in all learning settings. in addition to taught students, this study investigated the impact covid- lockdown had on pharmacy trainees. most colleges have pulled back their students, in fear for their safety, for approximately half a term. for this period, trainees were offered alternative online activities. while this period may represent a small portion of the pharm d training duration, it represents approximately a quarter of the b pharm training duration. majority of graduates believe this will not have a negative impact on their practice as pharmacists. however, a small proportion (% %) of graduates are concerned by the limited interactions they have had with employers in the pharmaceutical industry, and thus fear a lower chance of employment in the foreseeable future. furthermore, the impact of lockdown on employment rates in the pharmaceutical industry is still unknown. this study shows that during the lockdown period, several clos have not been completely covered, especially psychomotor based ones. in addition, many teachers believe that students have not been able to attain all essential knowledge and skills to cover all basis. both teachers and students have expressed interest in holding revision sessions in the upcoming year, program management teams are encouraged to design and schedule a number of temporary short courses to mend this issue. employment rates of graduates is a program key performance indicator and must be monitored for ncaaa program accreditation. nevertheless, alumni committees must increase their efforts in guiding fresh graduates seeking employment. . recommendation for developing a contingency strategy for emergency remote teaching: although pandemics are thankfully rare, other situations may also call for emergency remote teaching, another recent example for saudi arabia is the impact of the gulf war ( - ) on educational institutions. while recorded news of school and university closures are available, limited research was performed on the impact of the war on education as well as future plans to adapt with similar circumstances. to avoid missing such opportunity, and in preparation for a possible lockdown extension, the author encourages educational program management teams across the country to explore the possibility of putting in place a contingency strategy for emergency teaching. this may include: creating a contingency course specification (ccs), a short document that outlines appropriate student-oriented teaching strategies and assessment methods to be used for each clo in crises times. ccs may also be used to define clos that may be successfully completed under lockdown circumstances, while outlining a plan for the completion of other learning outcomes postlockdown. for example, such clos may be incorporated into related courses or made into a short compulsory course. creating an overall timeline map of all required assessments to be completed by students from each level or program year, thus, to help coordinate coursework between different courses and to ensure sufficient time is given for completion without overloading students. to further investigate attainment of program learning outcomes, an additional post-lockdown traditional assessment may be utilized. analysis from such assessment may be used to design short comprehensive summer courses to further correct student deviation from the program plan. long term recommendations to enhance the efficiency of contingency strategy may include: further improving the infrastructure for distance learning, based on stakeholders' experiences during the lockdown period. providing training and technical support to all faculty members in effective use of distance educational tools for studentoriented teaching and assessment strategies. this may come in the form of a compulsory online course in alignment with preparing new phd graduates to teach at university level. integrating available learning management systems (lms) into the normal routine of daily teaching and assessment process. this will facilitate a better digital environment for student-teacher and student-student interactivity, as opposed to using emails and phone-based communications. while this will help monitor in-process quality of education, it will also allow for data collection and thus research and development of education. to better equip final year students for pre-registrational training under special circumstances, program managements are encouraged to introduce compulsory requirements of volunteer training hours for students of senior levels. . . . board of deans for the colleges of pharmacy in ksa . . . . recommendation for collaborative initiatives:. education based collaborations between colleges of pharmacy in saudi arabia are still developing. a great initiative of collaboration has started after the formation of a board of deans for pharmacy colleges in saudi arabia. this had a positive impact on the standardisation of goals for pharmacy programs. nevertheless, a greater interaction is needed between pharmacy colleges to further push pharmacy education forward to maintain a high calibre of pharmacy gradu-ates. therefore, the author recommends the formation of a broader organisation such as ''saudi association of colleges of pharmacy" (sacp). this may also further quality of teaching and research efforts as well help to absorb the impact of crises. the covid- pandemic had a significant impact on pharmaceutical education in saudi arabia. while all teaching processes were forced to be distant, the ministry of education has led educational institutions across the country to a successful completion of the semester. this extraordinary situation called for a study to investigate student satisfaction with the emergency education processes conducted during this time. the use of online virtual classrooms, as a substitute for face-to-face traditional teaching, came with its challenges. the most significant was the limitations of student-student and student-teacher interactions. to overcome this challenge, the author recommends the implementation of various student-centred teaching strategies where proactive learning is encouraged. assessment via alternative methods during the lockdown has alerted teachers to the importance of their use in normal circumstances, as they can have a positive effect on students clo based skills. nevertheless, as students have less experience in working with alternative assessment methods, it is important they are accompanied by a student friendly guide to help them better understand the required actions and the marking scheme. the author of this study declares no competing financial interests or personal relationships that may have influenced the study performed in this paper. accreditation council for pharmacy education', accreditation council for pharmacy education pharmacy education in saudi arabia: the past, the present, and the future implementation of an acpe-accredited pharmd curriculum at a saudi college of pharmacy emerging frontiers of pharmacy education in saudi arabia: the metamorphosis in the last fifty years transactional distance and interactive television in the distance education of health professionals problem-based learning: a paradigm shift or a passing fad? overview of theories and principles relating to characteristics of adult learners assuring excellence in distance pharmaceutical education likert scale: explored and explained accreditation and student assessment in distance education: why we all need to pay attention t test as a parametric statistic points of significance: visualizing samples with box plots variations of box plots pharmacy student engagement, performance, and perception in a flipped satellite classroom performance indicators of higher education in saudi arabia saudi health work force over the next years a simple more general boxplot method for identifying outliers years of boxplots the author would like to thank the college of pharmacy at taibah university (al madinah al munawarah, ksa) represented by prof. saleh bahashwan the college dean, and the vice deanery for educational affairs represented by dr. sultan s. althagfan the vice dean for academic affairs.the author is very grateful to the recently graduated pharmacist azzam alghamdi and the undergraduate pharmacy students mr. muhanad algamdi and mr. ahmad haidar al-hrazi for participating in the student interviews. the author is also thankful to dr. sultan althagfan prof. khairy gabr, dr. ahmed effat and dr. rawan saeed bafail for taking part in the teachers' interviews.the author is also very thankful to dr. fatma al qudsi, mrs. somaiah alqurashi, mr. ibrahim alqurashi, mis. abrar alqurashi and mr. yahya alqurashi for their early contributions in developing the questionnaire of this study. key: cord- -k s iy u authors: khalafalla, abdelmalik i.; lu, xiaoyan; al-mubarak, abdullah i.a.; dalab, abdul hafeed s.; al-busadah, khalid a.s.; erdman, dean d. title: mers-cov in upper respiratory tract and lungs of dromedary camels, saudi arabia, – date: - - journal: emerg infect dis doi: . /eid . sha: doc_id: cord_uid: k s iy u to assess the temporal dynamics of middle east respiratory syndrome coronavirus (mers-cov) infection in dromedary camels, specimens were collected at – month intervals from independent groups of animals during april –may in al-ahsa province, saudi arabia, and tested for mers-cov rna by reverse transcription pcr. of live camels, ( . %) nasal swab samples were positive; of camel carcasses, ( . %) lung tissue samples were positive. positive samples were more commonly found among young animals (< years of age) than adults (> years of age). the proportions of positive samples varied by month for both groups; detection peaked during november and january and declined in march and may . these findings further our understanding of mers-cov infection in dromedary camels and may help inform intervention strategies to reduce zoonotic infections. m iddle east respiratory syndrome coronavirus (mers-cov) is an emerging pathogen associated with severe respiratory symptoms and renal failure in infected persons ( , ) . saudi arabia is the country most severely affected by the virus and is where the first recognized case was identified in . the origin of mers-cov remains a mystery. bats seem to be the reservoir host of the virus ( ) but are probably not the source of the ongoing mers-cov outbreak because of limited contact with humans in the arabian peninsula. early observations that some mers-cov-infected persons had been exposed to camels suggested a possible role of these animals as intermediate reservoir hosts ( , ) . serologic surveys subsequently conducted in several countries in the arabian peninsula and africa identified high rates of mers-cov-specific antibodies in dromedary camels ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) . furthermore, mers-cov infection in dromedary camels was definitively proven by the detection of virus and virus sequences in respiratory specimens, feces, and milk collected from camels in qatar ( , ) , oman ( ) , saudi arabia ( , , ) , and egypt ( ) . the few published studies that looked for mers-cov in the respiratory tract of naturally infected dromedary camels examined nasal or ocular swab samples but not samples from the lower respiratory tract. moreover, several studies relied on only a few specimens or collected specimens at only time point ( , ( ) ( ) ( ) . to address these limitations and to clarify the dynamics of mers-cov infection in these animals, we conducted a year-round study in which we collected a large number of specimens from the upper respiratory tracts of live dromedary camels and from the lungs of dromedary camel carcasses. this study was approved by the institutional review board of the camel research center, king faisal university, al-ahsa, saudi arabia. respiratory specimens were collected from independent groups of mixed-age dromedary camels (camelus dromedaruis). the first collection was obtained during april -may at the al omran abattoir, al omran city, in al-ahsa province in the eastern region of saudi arabia. livestock slaughtered at this abattoir include cattle, goats, sheep, and camels originating from al-ahsa and neighboring provinces. animals selected for slaughter were mainly from the livestock market and from herds located around al-ahsa province. at the livestock market in al-ahsa, dromedary camels are housed in small groups ( - animals), where they may stay for no more than days. they are then transported in vehicles to the abattoir, where they are kept for no more than hours before slaughter. samples were taken from slaughtered dromedary camels on occasions (every - months). on each particular collection date, tissue specimens were collected from the lungs of all slaughtered dromedary camels. a total of animal carcasses were sampled; had been young animals (< years of age) and had been adults (> years of age). lung lobes that showed pulmonary lesions were sampled; if both lobes showed lesions or if no lesions were visible, the left lobe was sampled because of its close proximity to the person collecting the sample. the tissue samples (≈ - g) were collected aseptically from inside the lung lobes by using sterile surgical instruments (scalpels, forceps, and scissors). to avoid cross-contamination, lungs were moved to a clean room adjacent to the slaughtering hall and examined on a freshly disinfected table by a person wearing a newly donned gown, face mask, and sterile gloves and using a new set of sterile surgical instruments. collected tissue samples were immediately deposited in labeled sterile plastic bags and placed in a cooler containing ice packs for transport to the laboratory. a second sample was collected from age-matched animals over the same period and consisted of nasal swab specimens ( young animals and adults), from visually healthy dromedary camels and from camels with nasal and lachrymal discharge. nasal swabs were collected from animals at locations in al ahsa province (al omran abattoir, al ahsa livestock market, and the veterinary hospital of king faisal university). for this procedure, a long sterile flexible swab was inserted into nostril until slight resistance was felt; the swab was then rotated, held in place for seconds, withdrawn, and placed in ml of cold viral transport medium containing antibiotics (this medium was chosen to enable future attempts to isolate the virus). both swab and lung specimens were transported on ice to the laboratory within - hours of collection and stored at − °c until testing. collection dates and numbers of samples are listed in table . swab specimens in transport media were mixed and then clarified by centrifugation at × g for minutes; the supernatants were recovered for extraction. lung samples were thawed and homogenized by using a tissueruptor homogenizer (qiagen, hilden, germany), and % suspensions were prepared in ml of transport medium. the resulting homogenates were subjected to centrifugation as above, and the supernatants were recovered for extraction. total rna was extracted from μl of each nasal swab or lung sample by using the qiaamp viral rna mini kit (qiagen) according to the manufacturer's instructions. extracted rna was tested by using a gel-based pancoronavirus reverse transcription pcr (rt-pcr) assay according to the protocol of vijgen et al. ( ) . realtime rt-pcr (rrt-pcr) was performed by using an assay kit provided by the centers for disease control and prevention (cdc; atlanta, ga, usa). this assay panel targets the mers-cov nucleocapsid protein gene ( ) and a region upstream of the envelop protein gene described by corman et al. ( ) . all samples were screened by using gel-based rt-pcr and rrt-pcr assays and were considered positive for mers-cov if a positive result was obtained with at least of the tests following world health organization recommendations (http://www.who.int/csr/disease/coronavirus_infections/ who_interim_recommendations_lab_detection_mer-scov_ .pdf). all rt-pcrs included no-template negative controls and quantified mers-cov transcript as positive control. cdna was prepared from positive samples and shipped to cdc for independent confirmation and sequencing. to assess the genetic variability of mers-cov, we sequenced the spike protein gene coding region ( , nt) on the positive samples. sequencing was performed on an applied biosystems xl genetic analyzer (thermo fisher scientific, grand island, ny, usa) by using sequencher version . software (gene codes, ann arbor, mi, usa) for sequence assembly and editing. sequence alignments were performed by using clustalx version . implemented in bioedit version . . (http://www.mbio. ncsu.edu/bioedit/bioedit.html). phylogenetic analyses were performed by using mega version . (http://www. megasoftware.net). the neighbor-joining method (tree algorithm inferred with the kimura -parameter substitution model of sequence evolution) was used to construct phylogenetic trees, and bootstrap resampling analyses were performed ( , replicates) to test tree reliability. during the study, a total of lung tissue samples and nasal swabs were obtained from the groups of camels (table ) (table ) . all animals from both groups appeared healthy on visual inspection except for . these -month-old dromedary camel calves, located outside of the al omran abattoir, exhibited purulent nasal and lachrymal discharge; mers-cov rna was detected in nasal swab specimens from these calves (figure ). mers-cov rna was more often detected in the lung and nasal cavity of young camels than adult camels (table ) our results confirm previous reports documenting wide circulation of mers-cov in dromedary camel populations in the middle east. in other studies, rt-pcr detection of mers-cov in nasal swab specimens from these animals has ranged from . % to . %. studies conducted in qatar detected mers-cov in ( . %) of ( ) and ( . %) of ( ) animals tested; in saudi arabia, ( %) of ( ) and ( %) of ( ); in oman, ( . %) of ( ) ; and in egypt, ( . %) of ( ) . a recent large study of , dromedary camels in the united arab emirates identified mers-cov rna in only . % of animals ( ) . of note, these authors found proportionately more positive animals near the border with saudi arabia and detected > fold more among animals sampled from slaughter houses. overall, we detected mers-cov in the upper respiratory tract of a higher proportion of animals tested in al-ahsa, but this proportion was within the upper range previously reported. in contrast, alagaili et al. ( ) , in a comprehensive survey conducted in november and december , sampled regions of saudi arabia (gizan in the south, taif in the west, tabuk in the north, uniza in the center, and hofuf [al-ahsa] in the east) and reported % positivity by rrt-pcr in animals from taif versus only % from al-ahsa, despite seroprevalence of % in the latter. during the same period and in the same region, we detected mers-cov in . % of nasal swab samples. this difference may be because of differences in the numbers and ages of animals sampled, time of specimen collection, or even between geographically proximate dromedary camel herds where rates of mers-cov detection can vary dramatically ( ) . of note, detection of mers-cov rna by rt-pcr does not necessarily indicate active virus replication. when dromedary camels were experimentally inoculated, infectious mers-cov was detected in the upper respiratory tract for only days, but rna could be detected by rt-pcr for up to days after inoculation ( ). we were unable to perform virus isolation studies because of lack of suitable biosafety infrastructure. we also found that a high proportion of lung tissues from slaughtered dromedary camels at the al omran abattoir were mers-cov positive by rt-pcr. in their experimental inoculation study, adney et al. ( ) observed histologic lesions in the epithelium of the upper and lower (trachea, bronchi, and bronchioles) respiratory tract and recovered viable virus from these tissues and from of lung lobes of an animal euthanized days after inoculation; viable virus was not recovered from tissues of other animals at and days after inoculation. although that limited study found infection extending to the lung of animal, the authors found that the upper respiratory tract was the predominant site of virus replication and offered that finding as an explanation for the lack of observed systemic illness among naturally infected dromedary camels. an alternative hypothesis posits that, in the natural setting, subclinical mers-cov infection of the lower respiratory tract also occurs, possibly enhanced by crowding and stress endured during transport and corralling before slaughter. although we did not collect matching premortem nasal swab samples from slaughtered animals to determine how many were also positive for mers-cov in the upper respiratory tract, our findings raise the possibility that testing upper respiratory tract samples alone may underestimate the true number of actively infected animals. in humans, mers-cov was detected in the lower respiratory tract of infected patients for ≈ month while oronasal swab samples were negative ( ) . likewise, mers-cov detection has been found to be enhanced from lower respiratory tract specimens, and therefore these specimens are recommended by the world health organization for diagnosis of mers-cov infection ( , , ) . although great care was taken to avoid contamination with ambient mers-cov present in the abattoir, the possibility that sample contamination occurred cannot be entirely ruled out. further studies that include immunohistologic examination and virus isolation from the lower respiratory tract of naturally infected dromedary camels will be needed to substantiate these findings. our detection of mers-cov rna in camel calves with purulent nasal discharge was consistent with those of hemida et al. ( ) , who also observed mild clinical signs characterized by nasal discharge in some naturally infected young dromedary camels, and of adney et al. ( ) , who documented appearance of purulent nasal discharge in the experimentally infected adult dromedary camels. we also detected mers-cov rna in a higher proportion of specimens from younger than from older adult dromedary camels, consistent with findings of previous studies that mers-cov infection is more common among young camels ( , ) . our study also investigated temporal variation in mers-cov infection in dromedary camels. although data interpretation was complicated by discontinuity in the months sampled and sampling from only animal group in some months, a temporal pattern in mers-cov prevalence was apparent. for both animal groups, peak detection occurred during november -january , followed by a steady decline, reaching the lowest point in may . although we observed no clear temporal differences in the geographic origins or ages of dromedary camels brought to slaughter, which might bias these results, our data are nevertheless limited and should not be used to imply a general pattern of mers-cov circulation in dromedary camels in saudi arabia. nevertheless, these findings would not be unexpected. increased circulation of mers-cov among dromedary camels during the cool season is consistent with the prevailing cooler ambient temperatures, which have been shown to enhance coronavirus survivability outside the host ( , ) , and the cool season is the period of peak circulation of other respiratory viral pathogens of humans in saudi arabia ( ) ( ) ( ) . this period also corresponds with the peak calving season for dromedary camels in saudi arabia ( ) ; higher rates of mers-cov infections among a greater proportion of young animals with higher virus loads may increase opportunities for virus spread ( , ) . whereas the link between dromedary camels and mers-cov infection of humans is well established ( , ) , the overall contribution of zoonotic infections to community-acquired mers-cov remains unclear. serologic studies of animal handlers in saudi arabia who work emerging infectious diseases • www.cdc.gov/eid • vol. , no. , july in close proximity to dromedary camels have shown limited evidence of mers-cov infection ( ) ( ) ( ) . alghamdi et al. ( ) , who examined patterns of mers-cov infections among humans in saudi arabia between june and may , did not find a concomitant temporal increase in human infections that corresponded with our findings in dromedary camels. those authors observed a slight, temporary increase in cases among humans in june and september and few cases from october through february, after which cases and deaths sharply increased beginning in april . the authors concluded that lower relative humidity and higher temperatures during these months might have contributed to the dramatic surge in reported cases. however, more recent data from the world health organization ( ) show a sharp decline in mers-cov cases among humans in may ; low numbers of cases were reported from june through august , when mean temperature was highest and relative humidity was lowest in saudi arabia ( ) . moreover, a recent increase in numbers of mers-cov cases in humans from september through february corresponds more closely with the temporal pattern we found in dromedary camels the preceding year. further studies conducted over multiple years are needed to better understand the ecology of mers-cov, which might help inform intervention strategies to reduce zoonotic infections. isolation of a novel coronavirus from a man with pneumonia in saudi arabia clinical features and virological analysis of a case of middle east respiratory syndrome coronavirus infection middle east respiratory syndrome coronavirus in bats, saudi arabia recovery from severe novel coronavirus infection middle east respiratory syndrome coronavirus infection in dromedary camels in saudi arabia seroprevalence in domestic livestock in saudi arabia seroepidemiology for mers coronavirus using microneutralisation and pseudoparticle virus neutralization assays reveal a high prevalence of antibody in dromedary camels in egypt middle east respiratory syndrome coronavirus (mers-cov) serology in major livestock species in an affected region in jordan middle east respiratory syndrome coronavirus (mers-cov) rna and neutralising antibodies in milk collected according to local customs from dromedary camels geographic distribution of mers coronavirus among dromedary camels antibodies against mers coronavirus in dromedary camels seroepidemiology of middle east respiratory syndrome (mers) coronavirus in saudi arabia ( ) and australia ( ) and characterization of assay specificity middle east respiratory syndrome coronavirus in dromedary camels: an outbreak investigation middle east respiratory syndrome coronavirus (mers-cov) in dromedary camels human infection with mers coronavirus after exposure to infected camels, saudi arabia mers coronavirus in dromedary camel herd, saudi arabia mers coronaviruses in dromedary camels a pancoronavirus rt-pcr assay for detection of all known coronaviruses real-time reverse transcription polymerase chain reaction assay panel for middle east respiratory syndrome coronavirus detection of a novel human coronavirus by real-time reverse-transcription polymerase chain reaction structure of mers-cov spike receptor-binding domain complexed with human receptor dpp prevalence of middle east respiratory syndrome coronavirus (mers-cov) in dromedary camels in abu dhabi emirate replication and shedding of mers-cov in upper respiratory tract of inoculated dromedary camels mers-cov study group. clinical features and viral diagnosis of two cases of infection with middle east respiratory syndrome coronavirus: a report of nosocomial transmission severe respiratory illness caused by a novel coronavirus stability of middle east respiratory syndrome coronavirus (mers-cov) under different environmental conditions t he effects of temperature and relative humidity on the viability of the sars coronavirus viral aetiology and epidemiology of acute respiratory infections in hospitalized saudi children respiratory viruses in children attending a major referral centre in saudi arabia viral agents causing acute lower respiratory tract infections in hospitalized children at a tertiary care center in saudi arabia evidence for camel-to-human transmission of mers coronavirus investigation of anti-middle east respiratory syndrome antibodies in blood donors and slaughterhouse workers in jeddah and makkah, saudi arabia, fall sparse evidence of mers-cov infection among animal workers living in southern saudi arabia during . influenza other respir viruses lack of middle east respiratory syndrome coronavirus transmission from infected camels the pattern of middle east respiratory syndrome coronavirus in saudi arabia: a descriptive epidemiological analysis of data from the saudi ministry of health middle east respiratory syndrome coronavirus (mers-cov): summary of current situation, literature update and risk assessment we thank isam al jalii and khalid borsais for assistance with sample collection and marzooq m. al eknah for financial support.dr. khalafalla is professor of veterinary virology at king faisal university, al-ahsa, saudi arabia. his research focus is on viral diseases of dromedary camels. key: cord- - xjc yq authors: adegboye, oyelola a.; elfaki, faiz title: network analysis of mers coronavirus within households, communities, and hospitals to identify most centralized and super-spreading in the arabian peninsula, to date: - - journal: can j infect dis med microbiol doi: . / / sha: doc_id: cord_uid: xjc yq contact history is crucial during an infectious disease outbreak and vital when seeking to understand and predict the spread of infectious diseases in human populations. the transmission connectivity networks of people infected with highly contagious middle east respiratory syndrome coronavirus (mers-cov) in saudi arabia were assessed to identify super-spreading events among the infected patients between and . of the mers cases recorded during the study period, ( . %) cases were linked to hospital infection, out of which ( . %) cases occurred among healthcare workers. there were isolated cases while the number of recorded contacts per mers patient is between (n= ) and (n= ), with a mean of . (sd = . ). five super-important nodes were identified based on their high number of connected contacts worthy of prioritization (at least degree of ). the number of secondary cases in each sse varies (range, – ). the eigenvector centrality was significantly (p < . ) associated with place of exposure, with hospitals having on average significantly higher eigenvector centrality than other places of exposure. results suggested that being a healthcare worker has a higher eigenvector centrality score on average than being nonhealthcare workers. pathogenic droplets are easily transmitted within a confined area of hospitals; therefore, control measures should be put in place to curtail the number of hospital visitors and movements of nonessential staff within the healthcare facility with mers cases. middle east respiratory syndrome coronavirus (mers-cov) is a contagious respiratory pathogen that is contracted via close contact with infected individuals. interactions among individuals can aid super-spreading of infectious diseases in humans or animals, and it is usually highest among individuals in close proximity with one another. mers-cov was first reported in a -year-old man in bisha area of the kingdom of saudi arabia in [ ] . it has now spread across countries in continents. e most index case-patients have either resided in or have travelled to areas neighbouring the arabian peninsula [ ] . from the intermittent transmission that had occurred in animal-to-human [ , ] , many human-to-human cases have also been documented within families and healthcare facilities [ ] [ ] [ ] [ ] [ ] . during an infectious disease outbreak such as mers-cov (or mers for short), the transmission usually forms networks of infected individuals (cluster of outbreaks) probably because of the way the virus crosses from one infected individual to another susceptible individual. in other words, the source of infection may be the direct or indirect connection [ ] . in network analysis, the aim is to identify the most crucial infected patients (also called nodes), who are important in the super-spreading and to use the location of the node in the network to predict which patients (nodes) are likely to be infected [ ] . ese important patients are influential in that they infect disproportionately large numbers of secondary contacts [ , ] . super-spreading events (sses) are as a result of individuals (agents of sse) harbouring the virus who infect disproportionately more secondary contacts, as compared to most others [ , , ] . erefore, an sse consists of a large cluster of infection in which some individuals infect many more other individuals, thereby acting as agents for an sse. in this study, super-spreading was defined as having at least five contacts. sses have been documented in other infectious disease outbreaks such as sars in beijing [ ] and more recently ebola in west africa, - [ , ] , and mer-cov in south korea, [ ] . e knowledge of people's connectivity network is very crucial in the spread of infectious diseases transmitted via pathogenic droplets such as respiratory infection, mers, and ebola. as in the case of mers, occasional larger cluster sizes should not be unexpected, such as the outbreak in south korea [ ] . although there have been variations in the size of human-human transmission of mers, its high variability and heterogeneity in the transmission potential have been underscored [ , ] . over the years, researchers have been exploring how the knowledge of network structures could influence public health measures. for example, network analysis based on connectivity centrality was used to identify high-risk people for targeted vaccination in an effort to contain the spread of infectious disease [ ] . network analysis was used to investigate whether the density of the network contacts of persons infected by mycobacterium tuberculosis was more likely to be tested positive for tuberculosis (tb) compared to the occurrence of tb clusters detected through network connections with clusters detected by molecular genotyping [ ] . similarly, the effect of protein-protein interactions within the host-pathogen interactome was explored via network analysis on pathogen fitness during infection [ ] . e focus of this study was to map and measure relationships and flows between people infected with mers and to investigate the structure of mers transmission with the help of network and graphs. patient's interactions and links were obtained through contact tracing within days prior to the onset of the disease. e structure of network connectivity will assist in identifying the most influential contacts, while network centrality metrics were used to investigate the contribution and characteristics of the agents of super-spreading to the infection and spread of mers. and lastly, the role played by patient's attributes (node property) was investigated as an epidemic amplifier or attenuator via hypotheses testing. is study is based on case-by-case list of clinical-confirmed mers cases provided by dr. rambaut [ ] . e focus is on the mers cases reported in the kingdom of saudi arabia between june and september . e variables considered in this study were age, gender, patient type (whether the patient is a healthcare worker (hcw) or nonhealthcare worker), health outcome (dead or alive) as at the last day of follow-up, patient comorbidity status, types of exposure to known risk factors (animal contact and camel contact indirectly or directly or through consumption of camel products), and place of infection (classified as hospital, community, and household/ family). e data set was cross validated with information from who disease outbreak news and saudi arabia moh mers command and control website. e kingdom of saudi arabia (ksa) is the main part of the peninsula bounded by the red sea on the west, gulf of aden on the south, gulf of oman on the south east, and arabian gulf on the east. e ksa measures about , , square kilometres and shares its border with several countries, such as jordan and iraq in the north, qatar, bahrain, kuwait and united arab emirates in the east, and oman and yemen in the south. e country is situated on latitude . - . and longitude . - . ( figure ). e ksa is divided into regions (manatiq, administrative level ) and governorates (muhafazat, administrative level ). e world bank as of estimated its population to be . million [ ] . variables. mers patients were clinically confirmed via realtime rna-positive strand virus using reverse transcription polymerase chain reaction (rt-pcr) with a positive pcr on at least two specific genomic targets, upstream e protein (upe) and orf a, or a single positive target (upe) with sequencing of a second target rdrpseq assay or n gene (nseq assay) [ , ] . patients' contact investigation was conducted by hospital officials by tracing patient's history of exposure to other known risk factors such as contact with other laboratory-confirmed mers cases, animal/camel contact, or visiting other places known to be linked to mers cases days prior to the onset of symptoms. an animal contact patient implies a patient with historical contact with animals, while camel contact patients were those who work in a camel market or have history of contact with camels, or consumed camel products in days prior to the onset of symptoms. a healthcare worker is anyone who works in a healthcare facility (all personnel, such as doctors, nurses, laboratory staff, securities, and receptionists). a patient is said to have comorbidity if he or she has coexisting chronic diseases or medical conditions or has been admitted to the hospital due to unrelated medical conditions. place of exposure is classified as (a) hospital infection if the infection occurred in a hospital, for example, a healthcare worker/hospital visitor/outpatient contracting the disease in a healthcare facilities, (b) family infection if the infection was through a family member or within the household, or (c) community infection if the infection is contracted outside the hospital or household, such as in schools, workplace, hajj tents, etc. descriptive analysis was conducted on some sociodemographic variables presented as mean and standard deviation for age and frequencies and percentages for other categorical variables. prevalence of mers disease across communities, household, and hospitals was tested via the chi-square statistic for categorical variables while the t-test was used for continuous variables (table ) . e units of network analysis in this study are the nodes representing individuals infected with mers within families, hospitals, or communities which are connected via edges. e outbreak network visualization and network analyses were conducted in r package "igraph" [ ] and ucinet . version . [ ] . we used centrality metrics to measure the structural importance of patients (nodes) in a network. e node "degree centrality" was used to reveal the most active nodes in the network and how well a node is connected with its neighbours-a node degree is the number of edge incidents on a node. e "betweenness centrality" was used to measure how many pairs of nodes a node can be connected to through a shortest path, while the "closeness centrality" was used to measure how contagious an infected patient (a node) is to others [ , , , ] . similarly, " -reach centrality" was used to explore the proportion of nodes that can reach a given node in steps or less while "eigenvector centrality" was used to measure the importance of a node depending on the importance of its neighbours. finally, the effects of patient's attributes on their position in a network (measured by network centrality metrics) were investigated, and the relationship between two (or more) network centrality metrics was explored. we used permutation tests in ucinet . version . [ ] to test specifically the following aspects: ( ) whether more central patients are hcws or not, ( ) whether more central figure ). mers fatality increases with age, % of the infection occurred in older males aged - years and more fatal in older men (above years). similarly, % of fatality in females occurred in women above years. a high proportion (about %) of patients had some kind of prior medical condition (comorbidity). e number of patients with comorbidity varied slightly across the regions. ere was higher fatal outcome in patients with comorbidity than patients without any comorbidity. about % of those with some kind of medical condition died of the disease compared to only % of patients without medical condition. e results showed that about half of cases ( ( . %)) were linked to at least one place of exposure where ( . %) of them were linked to hospital outbreaks (table ) . ere were ( . %) cases, whose contact history of infection was unknown. of the cases linked to hospital outbreaks, more than one-third (n � ) occurred among healthcare workers, indicating that about . % of all cases involving healthcare workers happened in the hospital (data not shown in table ). figure : illustration of (a) degree-, (b) betweenness-, (c) closeness-, and (d) eigenvector-centrality metrics for sample mers infection network. each of the patient number represents a node connected by links called edges. e square nodes represent males while the circle nodes represent females. grey represents healthcare workers and dark colours are nonhealthcare workers while white is unknown. e node sizes indicate the centrality values in table . e contact structure of mers cases in the ksa between june and september is displayed in figure . isolated nodes (n � ( . %)) with degree of zero are not shown in the figure. ere were isolated cases while the number of recorded contacts per mers patient is between (n � ) and (n � ), with a mean of . (sd � . ). ere were a total of connections- primary cases and secondary cases. e majority of the first line secondary cases did not produce any further secondary cases of their own. e largest cluster has a wheeland-spoke configuration in which patient number is in the centre and linked to other secondary cases ( . % of the total cases in the network) (figure ). e results showed that most of the outbreaks occurred in the hospital (indicated by dark line in figure ) and that most of the infected patients were nonhealthcare workers with comorbidity (indicated by green nodes in figure ). table presents the measures of network centrality estimates for the most important nodes (subsequently called patients) selected by each network metric. a total of nodes worthy of prioritization were selected based on these network metrics (table ). it was revealed that out of ( %) of the cases are healthcare workers and ( . %) cases had some kind of comorbidity. about half of the prioritized nodes (n � ( . %)) occurred in hospital settings while ( . %) cases were fatal. based on degree centrality metrics, the top five most important cases were identified based on at least five secondary cases, indicating their high number of connected contacts worthy of prioritization (table ). e number of secondary cases in each sse varies slightly (range, - ). closeness and -reach network metrics ranked the same patients ( , , , , , , , , , and ) among the top cases worthy of prioritization while the eigenvector metrics list was also very similar. e betweenness scores, which indicate the number of other nodes infected by the given node, indicated that patient , , , , and had the top highest betweenness score of a range of to . among the important cases according to degree centrality, four resulted in fatality. patient was favoured (based on degree, closeness, betweenness, and eigenvector network centrality metrics) as the most important in the transmission network by having the highest number of secondary cases. however, the cases selected using betweenness centrality were slightly different from other metrics with patient topping the list. e degree and betweenness centrality estimates are depicted in figures (a) and (b), respectively. e larger node area shows the level of worthiness of prioritization. centrality. when network centrality metrics were used to investigate the association between patient's attributes and patient's position in a network, only eigenvector centrality was significantly associated with two patient's attributes. e eigenvector centrality was significantly (p < . ) associated with place of exposure, with hospital infection having on average significantly higher eigenvector centrality than other places of exposure. similarly, being a healthcare worker was significantly associated (p < . ) with eigenvector centrality. to answer the questions about the relationships among the network centrality metrics, the results suggest that patient's degree centrality explains . % of the variation in patient's closeness centrality, while % and . % of the variation in closeness centrality were explained by eigenvector and betweenness centrality, respectively. furthermore, we investigated whether super-spreading patients with high network centrality metrics (e.g., degree, betweenness, closeness, eigenvector, and -reach) have similar attributes. significant differences were observed in age, gender, healthcare worker, and fatal cases across the regions; however, no difference was observed in the proportion of patients with comorbidities. in this study, several network centrality metrics (degree, betweenness, closeness, eigenvector, and -reach) were used to quantify the connectivity among mers cases and to identify which patient requires prioritization for intervention. usually the patient with the highest degree has the most ties to other patients in the network [ ] . saudi arabia is said to be facing continuous risk of mers outbreaks [ ] . e findings emphasize the importance of patient's level characteristics in understanding their level of infectiousness. results show that healthcare facilities and healthcare workers are the most crucial factors in driving national epidemics of mers. although healthcare workers are at higher risk of mers infection due to their proximity to infected patients, previous studies have shown that cases among healthcare workers are less serious [ ] with few fatalities [ , ] . hospital infections display higher interconnectivity and, on average, are linked to patients that are more connected to highly connected patients than nonhospital infections. recent studies have reported the outbreaks of mers in hospitals [ , [ ] [ ] [ ] [ ] . e overcrowding in hospitals due to easy access to medical care caused mers to move quickly throughout korea [ ] . virtually, all cases of mers in korea occurred in a hospital-to-hospital type of transmission [ ] . similarly, healthcare workers are more connected to important nodes themselves than nonhealthcare workers. in terms of the number of connected contacts (via degree centrality), nodes , , , , and were the top most active mers cases, but they do not reflect the spread of mers. e most influential node is patient based on degree centrality. most of the secondary cases connected to patient were either attended to by the same healthcare worker(s) or are themselves healthcare workers that attended to patient . patients who are strongly tied in a network are more likely to be similar to each other than different. patient was a -year-old female admitted to the hospital with unrelated symptoms [ ] , and she was associated with healthcare worker cases and household cases because many healthcare staff treated her at the initial stage during her hospitalization in a vascular surgery ward and initially in an open ward, stressing the importance of limiting access to other patients and quarantines. regarding infectivity, when determining the strength of a patient in a network through not only its connectivity but also the interconnectivity of its secondary cases, the betweenness metric provides better estimate. e low betweenness score of patient indicates that while patient connects many other patients, it is not a pathway to further infection. nodes , , , , and were identified as critical in the spread of mers to other cases using the betweenness metric. ese patients acted as a bridge connecting other smaller secondary cases and thus the spread of mers infection by further connecting with other secondary cases who also connect other important cases. it was found that the individuals who connect or more separate contacts have an increased likelihood to connect to multiple contacts [ ] . patient is a -yearold female with no comorbidities was linked to three secondary cases and five other indirect offspring. e major limitation in this study lies in the data sources and contact tracing accuracy. e analysis is based on retrospective data rather than prospective data collected from multiple sources which are publicly available. e accuracy of some of the information provided by the patient may not be verifiable especially during the early outbreaks; however, the reporting has been improved upon over the years with coordination between saudi ministry of health and regional who office. similarly, while it is acknowledged that most reported clusters occurred in the hospital as a result of contact tracing, this is not surprising because of adequate monitoring and data collection in the hospital that revealed large secondary cases in the healthcare facilities. lastly, as in the case of publicly available data, these study data are characterized by missing data. while the problems associated with inference-drawn, publicly available epidemiological data are acknowledged, the results are meaningful and suggest that structure and characteristics of contact network can indeed have significant effect on the rate of transmission of mers disease. e present study highlighted the importance of contact network in the spread of infectious disease. ese results provide interesting findings. ey show that real-time network analysis can provide insight into the structure of transmission of infectivity to identify important players for isolation and selective treatment. moreover, the results present rational estimate of the size of outbreak and the underlying structural characteristics of the group [ ] . patients with high degree of centrality played a powerful role as epidemic attenuators. patients with high degree of centrality played a powerful role as epidemic attenuators as they are linked to many secondary cases that did not produce any further secondary cases of their own. while patients with high betweenness are epidemic amplifiers, they are a pathway to infect other patients. is study has shown that most important nodes are those within the hospital, and healthcare workers are more prone to the infection. pathogenic droplets are easily transmitted within the confined areas of hospitals, and control efforts should be put in place at different layers of hospitals. reducing contact formation especially within the hospital by restricting hospital visitation for mers patient families and reducing the number of healthcare workers with access to mers patients will certainly have significant effect on the spread of mers disease. saudi arabia is said to be facing continuous risk of mers outbreaks [ ] . if control measures are not put in place to curtail the number of hospital visitors and movements of nonessential staff within healthcare facility, with their connectivity to people within the community, the disease will speed up further national/international outbreaks. future research should focus on epidemiological analysis exploring the role of a healthcare facility in the spread mers disease. e authors declare no conflicts of interest. mers coronavirus: diagnostics, epidemiology and transmission infectious diseases epidemic threats and mass gatherings: refocusing global attention on the continuing spread of the middle east respiratory syndrome coronavirus (mers-cov) transmission characteristics of mers and sars in the healthcare setting: a comparative study mers-cov outbreak following a single patient exposure in an emergency room in south korea: an epidemiological outbreak study mers outbreak in korea: hospital-to-hospital transmission epidemiological, demographic, and clinical characteristics of cases of middle east respiratory syndrome coronavirus disease from saudi arabia: a descriptive study e role of superspreading in middle east respiratory syndrome coronavirus (mers-cov) transmission spatial covariate adjusted survival rates for middle east respiratory syndrome (mers) coronavirus in the arabian peninsula transmission network analysis to complement routine tuberculosis contact investigations mers, sars, and ebola: the role of super-spreaders in infectious disease super-spreaders in infectious diseases superspreading sars events spatial and temporal dynamics of superspreading events in the - west africa ebola epidemic ebola superspreading assessing the risk of observing multiple generations of middle east respiratory syndrome (mers) cases given an imported case nuanced risk assessment for emerging infectious diseases infectious disease containment based on a wireless sensor system transmission network analysis in tuberculosis contact investigations centrality in the host-pathogen interactome is associated with pathogen fitness during infection mers-cov spatial, temporal and epidemiological information infection prevention/control and management guidelines for patients with middle east respiratory syndrome coronavirus (mers-cov) infection e igraph software package for complex network research ucinet for windows: software for social network analysis, analytic technologies network centrality and super-spreaders in infectious disease epidemiology a pandemic risk assessment of middle east respiratory syndrome coronavirus (mers-cov) in saudi arabia risks of death and severe disease in patients with middle east respiratory syndrome coronavirus spatial modelling of contribution of individual level risk factors for mortality from middle east respiratory syndrome coronavirus in the arabian peninsula building predictive models for mers-cov infections using data mining techniques description of a hospital outbreak of middle east respiratory syndrome in a large tertiary care hospital in saudi arabi hospitalassociated outbreak of middle east respiratory syndrome coronavirus: a serologic, epidemiologic, and clinical description e critical care response to a hospital outbreak of middle east respiratory syndrome coronavirus (mers-cov) infection: an observational study it feels like i'm the dirtiest person in the world.": exploring the experiences of healthcare providers who survived mers-cov in saudi arabia an assessment of the level of concern among hospital-based health-care workers regarding mers outbreaks in saudi arabia knowledge, attitude and practices of healthcare providers towards mers-cov infection at makkah hospitals, ksa disease outbreak news: middle east respiratory syndrome coronavirus (mers-cov)-saudi arabia using social network and ethnographic tools to evaluate syphilis transmission is study was supported by research grant qust-cas-spr- - from qatar university. e authors would also like to thank majeed adegboye for his help with the mers data management. high connectivity among healthcare workers and their proximity to mers cases is not surprising because of the nature of their job. in general, healthcare workers across saudi arabia have negative attitude toward mers infection [ , ] . although infectious disease epidemiological plans were put in place in some hospitals, outbreaks of mers still occurred due to the failure to adhere to the infection control measures [ ] . a high proportion of healthcare workers felt at risk of contracting the disease but obliged to care for mers patients [ , ] . similarly, a high percentage of healthcare workers do not feel safe at work using standard precautions [ ] . table . larger sized nodes implies (a) degree centrality and (b) betweenness centrality. e circle nodes are females while square nodes are males. e node colours represent contact history: pink is the index patient, green is hospital linked, blue is community or family linked, red denotes the primary contact, and white nodes represent unknown contact history. 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- -ppw s l authors: al ghobain, mohammed; aldrees, turki; alenezi, abdullah; alqaryan, saleh; aldabeeb, dana; alotaibi, najed; aldhabib, abdulrahman; alghalibi, shaker; alharethy, sami title: perception and attitude of emergency room resident physicians toward middle east respiratory syndrome outbreak date: - - journal: emerg med int doi: . / / sha: doc_id: cord_uid: ppw s l introduction. middle east respiratory syndrome (mers) outbreaks have had a considerable negative impact on health systems in saudi arabia. we aimed to study the psychological impact of a middle east respiratory syndrome coronavirus (mers-cov) outbreak on emergency room resident physicians (errps). methods. we assessed the mers-related psychological impact and concerns of errps using a self-report questionnaire. results. the majority ( %) of the errps agreed that their work put them at risk of infection, but most ( %) did not agree that they should not be looking after patients infected with mers. despite that, % of errps reported being afraid of contracting the infection from infected patients and only . % of them were willing to change their current job. the majority of the errps ( %) felt that their job would expose their families to risk of infection. conclusions. our study demonstrated the considerable psychological impact of mers outbreaks on errps. the errps' concerns and the psychological impact of mers outbreaks should be considered in greater detail by hospital policymakers. middle east respiratory syndrome (mers) is a deadly and contagious disease caused by a novel coronavirus (mers-cov) that has had an intensive impact on the healthcare system. the mers-cov can be transmitted in different ways, including direct contact with dromedaries, living with an infected person, or contact with infected persons inside healthcare facilities. the disease has a high mortality rate of up to % [ ] . according to the world health organization (who), mers is a threat to the entire world and thus needs prompt attention and action [ ] . mers was first identified in saudi arabia in [ ] . apart from saudi arabia, nearly countries including kuwait, qatar, indonesia, uk, uae, south korea, and usa have reported mers cases. the who has reported , laboratory-confirmed cases of infection with mers-cov, and there have been nearly deaths related to mers-cov since september [ ] . dromedary camels are the primary animal host for mers-cov [ , ] . people with mers have had a history of close contact with camels and drinking camel milk. however, human-to-human transmission has also been documented [ ] . the majority of patients who become infected with the virus in the community seek their initial medical help from primary healthcare centers or from the emergency department in which emergency staff, including emergency emergency medicine international physicians and nurses, are the first-line providers of care for suspected and unscheduled patients that require immediate attention. in addition, the emergency room resident physicians (errps) are at risk of falling ill from exposure to mers patients and the possibility of spreading the illness to their family members, which could affect their overall effectiveness and willingness to work during a mers outbreak. therefore, their anxiety and fears must be taken seriously and strategies should be incorporated to manage them. the mers outbreak in saudi arabia was a very good opportunity to explore these concerns. to the best of our knowledge, no study has explored errps' perceptions and attitude toward mers or the psychological impact of mers on errps in hospitals. thus, the present study aimed to assess the perceptions, attitude, and psychological impact of mers on errps. a cross-sectional study was conducted using a self-administered questionnaire. the study was conducted in the emergency department after obtaining ethical approval from the king saud university research center. all residents were informed regarding the purpose of the study and their verbal consent was given. the study was conducted in four tertiary care hospitals in riyadh, saudi arabia: king khalid university hospital, king fahad medical city hospital, king abdulaziz medical city hospital, and king faisal specialist. we included all errps working in these four hospitals between november and december after a major outbreak of coronavirus (mers-cov) in saudi arabia. data were collected using a self-administered questionnaire. the questionnaires were distributed and collected during the regular weekly residents' education activities. the questionnaire contained a brief description of the study's objectives and statements assuring participants of their anonymity and right to stop participating of their own volition. the questionnaire was adapted and modified, based on a review of the literature, from one used in a previous study by wong et al. [ ] . the questionnaire comprised two parts. the first part contained questions about participants' background information, including age, marital status, training level, and knowledge of mers. the second part comprised four main sections that included an assessment of ( ) work-related concerns, ( ) non-work-related concerns, ( ) the perceived impact of mers on errps, and ( ) their preparedness for a mers outbreak. all of the descriptive data were summarized as percentages and frequencies. categorical variables were compared using the chi-square test. all statistical analyses were performed using ibm spss statistics (ibm inc., armonk, ny). the total sample size of this study was errps (out of errps; response rate %). the errps had a mean age of years, % were male, and % were married. fifty-six percent of the errps rated their knowledge about mers-cov as inadequate while % had had direct contact with at least one patient infected with mers-cov (table ) . the majority of the errps ( %) agreed that their work put them at risk of infection, but most ( %) did not agree that they should not be looking after patients infected with mers. despite that, % of errps were afraid of contracting the infection from infected patients and only . % of them were willing to change their current job. the majority felt that their job would expose their families ( %), parents ( %), and close friends ( %) to risk of infection (table ) . table summarizes the perceived impact of mers-cov and readiness for an outbreak. of the errps, % would be afraid of telling their families about the risk of exposure, % agreed that there would be inadequate staff in the workplace to handle the increased demand, and % would feel more stressed at work. furthermore, % of errps had received infection control training and % reported that their hospitals have enough infection control staff to deal with such an outbreak. there were no significant differences in level of concern by rotation except that first year training levels residents were more likely to be afraid of being infected than other training levels ( < . ). there were also no significant differences in terms of knowledge of mers but respondents who had previously provided care for mers patients were more likely to agree that the job put them at risk and were more afraid of being infected ( = . and = . , respectively) (data not shown in tables). our study highlights the perceptions, attitude, and psychological impact of mers outbreaks among errps in saudi arabia. as mers was a new outbreak that began in saudi emergency medicine international arabia, to our knowledge, this was the first study to address the impact of a mers outbreak among errps. the findings of our study showed that the majority of errps believed that their work put them at risk of infection and they were afraid of contracting mers. the majority of the errps felt that their job would expose their families, parents, and close friends to risk of infection. a small pilot study conducted in a single center in jeddah, saudi arabia, in which the majority of respondents were nurses from the philippines, did address the emotions and coping strategies of the healthcare workers who faced a mers-cov outbreak. it was found that the main sentiments centered upon fear for personal safety and the well-being of colleagues and family. their fear was alleviated by positive attitudes in the workplace, clinical improvement of infected colleagues, and stoppage of disease transmission among healthcare workers after adopting strict protective measures. the most important emotion that drove them to continue working was their ethical and professional obligation toward their profession [ ] . our findings are similar to those of other non-mers viral outbreaks reported from different parts of the world. for instance, during the severe acute respiratory syndrome outbreak (sars) in , approximately two-thirds of healthcare workers in toronto experienced concern for their own or their family's health [ ] while % of healthcare workers in hong kong reported a high level of stress and % were found to have experienced psychological distress [ ] . a study of the psychological impact of the outbreak of sars on hospital employees in beijing, china, found that about % of the respondents had experienced high levels of posttraumatic stress symptoms [ ] . an interesting finding of our study was that most errps did not agree that they should not be looking after patients infected with mers. we think that these finding are reflections of the high standards of ethical values of errps and their professional obligation toward their jobs and patients. in contrast, a study conducted, in australia, anticipated a high rate of absenteeism among hospital staff, reaching up to % in response to influenza pandemic hypothesized survey scenario [ ] . more than half of errps had attended infection control training, and they reported that their hospitals had enough emergency medicine international infection control staff to deal with such an outbreak and their hospitals have a clear plan to handle a mers outbreak. this is a positive aspect and a positive learning experience from a mers outbreak as it reflects good preparation and a high level of awareness of dealing with such an outbreak. how hospitals plan to handle a mers outbreak was included but not limited to cancellation of outpatient clinics, visitor restrictions, mandatory wearing of protective measures (e.g., masks), limited hospital entrance, mandatory screening of suspect infected visitors, and public awareness and education. the limitations of our study include it having a crosssectional design, possible reporting bias, and being conducted in a single city in saudi arabia with a small sample size limited to a single profession (i.e., errps). however, the study was conducted in four major hospitals in saudi arabia that all treated and handled patients with mers infection, which justifies the generalization of our findings. we limited our study to errps, as we believe that they are the healthcare workers at the highest risk of exposure because they deal with suspected cases before the diagnosis is established. the sample size was representative and reflects the real number of errps working in these hospitals during the outbreak. our study demonstrated the considerable psychological impact of mers outbreaks on errps. the errps' concerns and the psychological impact of mers outbreaks should be considered in greater detail by hospital policymakers. no financial support was obtained for this study. middle east respiratory syndrome coronavirus (mers-cov)-saudi arabia isolation of a novel coronavirus from a man with pneumonia in saudi arabia middle east respiratory syndrome coronavirus (mers-cov) evidence for camel-to-human transmission of mers coronavirus mers coronaviruses in dromedary camels spread of mers to south korea and china concerns, perceived impact and preparedness in an avian influenza pandemic-a comparative study between healthcare workers in primary and tertiary care healthcare workers emotions, perceived stressors and coping strategies during a mers-cov outbreak psychosocial effects of sars on hospital staff: survey of a large tertiary care institution severe acute respiratory syndrome (sars) in hong kong in : stress and psychological impact among frontline healthcare workers the psychological impact of the sars epidemic on hospital employees in china: exposure, risk perception, and altruistic acceptance of risk how would australian hospital staff react to an avian influenza admission, or an influenza pandemic? this study was supported by the college of medicine research center, deanship of scientific research, king saud university, kingdom of saudi arabia. key: cord- -vwavivmo authors: mohsen alsufyani, abdulaziz; alforihidi, mohammed a.; eidah almalki, khalid; musaad aljuaid, sayer title: linking the saudi arabian vision with nursing transformation in saudi arabia: roadmap for nursing policies and strategies date: - - journal: int j afr nurs sci doi: . /j.ijans. . sha: doc_id: cord_uid: vwavivmo the saudi government is currently facing multiple challenges in achieving “the gold standard” in nursing practice. this is not limited to educational challenges, staffing shortage, paucity of international and national benchmark evidence, absence of clear and defined scope of nursing practice, and lack of appropriate policies and regulations. this study presented a comprehensive plan for developing a policy based on current challenges, recognition of policy goals, assessment of potential options and alternatives, identification of stakeholders, proposition of recommended solutions, and implementation of the framework to transform nursing standards and link these changes with the saudi vision . however, amendments are required in the present strategic plan for the better management of the nursing profession. it is doubtful that the current nursing profession status quo is capable of meeting the golden standards for health care. thus, the transformation of the nursing profession in saudi arabia is necessary. globally, nurses have made important contributions to a range of health priorities including universal health coverage, mental and community health, emergency preparedness and response, patient safety, and the provision of comprehensive patient-centered care however, saudi arabia has entered a new era of progress and prosperity after developing vision -a program that contributes a series of developments in the fields of health delivery systems, nursing, trade, education, communications, science, and technology. one of the goals of saudi vision is improving the health delivery system to enhance community health status. in this regard, the provision of free healthcare services in saudi arabia is the responsibility of the ministry of health (moh) at three care levels: primary, secondary, and tertiary . moreover, the government plays an essential role by offering varied levels of health services. in fact, the saudi government has spent sr billion from to in the healthcare sector to create , primary healthcare centers and hospitals . in saudi arabia, nurses make important contributions to the healthcare sector as healthcare providers. moreover, it is predicted that the demand for nurses in saudi arabia will be more than doubled by , as the annual population growth continues to increase at an annual rate of . %. this shows that almost , nursing positions should have been filled by . to meet this need without overseas recruitment, approximately , new nurses should graduate and be employed each year in saudi arabia. however, in juxtaposition with developed countries, saudi arabia faces extreme staffing shortages, socio-cultural challenges, paucity of international and national benchmark evidence, absence of clear and defined scope of nursing practice, and, most importantly, policies and regulations along with the ensuing repercussions on the quality of care being offered , . these hurdles inhibit the achievement of the "the gold standard" in nursing practice as promised by the saudi government. consequently, the nursing status quo contradicts the saudi vision regarding the enhancement of nursing working environment to retain and empower nurses. to undertake such challenges, the success of delivering "the gold standard" in nursing depends on whether the saudi government is vigilant, less centralized, smart, and sophisticated . in addition, nursing staff will have to be empowered to ensure appropriate decision-making in the right place at the right time. to this end, they need the authority to make choices, accept responsibility, and take action. therefore, this policy paper puts forth its emphasis on several extractable themes associated with nursing transformation in order to spell out the underlying nursing objectives proposed in the saudi vision. in islamic history, rufaida al-asalmiya was the first woman to practice nursing. as a nursing educator and counterpart to florence nightingale, she offered nursing care to injured soldiers in primitive tribes throughout the initial islamic period. in addition, she established a clinic for teaching nursing and offering nursing care to the community . eventually, in , nursing was established as a profession according to the moh. in addition, the collaboration between the who and the moh in led to the establishment of the "health institute program" for one-year in riyadh . as global health systems creak under the strain of the coronavirus, it has been made clear that there are not enough nurses to meet global and national health needs. in saudi arabia, the current shortage of nurses has led to the creation of many loopholes in quality of offered care, and has developed an acute prerequisite for expatriate nurses to meet the healthcare needs and reduce the impact of nursing paucity that has arisen in moh and other healthcare sectors. as shown in table , a total of , registered nurses are currently working in saudi arabia, which includes the private sector and other governmental agencies. in, , saudi nurses comprised . % of the total nurses᾿ population . more specifically they constituted . %, . %, and . % of the total nurses working in moh, other governmental hospitals, and the private sector, respectively. in addition, a ratio of . nurses per , individuals is represented in the population of saudi arabia, with an escalation of % from to . [insert table here] to provide more context, saudi arabia has the second highest ratio of nurses after qatar ( / , ) as compared to, jordan, bahrain, and uae that have lower nurse populations . when compared globally, the ratio of nurses in saudi arabia is still low as compared to france ( / , ), the united kingdom ( / , ), usa ( / , ), and canada ( / , ) . [insert figure here] however, besides the low ratio of nurses in saudi arabia, the sole reliance on the recruitment of expatriate nurses resulted in various challenges, including an escalated burden on the economy and unstable health care. in saudi arabia, nursing programs have had poor enrolment rates due to the bad reputation of the nursing profession across the community , . this bad reputation was stimulated by mixed working environments, cultural reasons, the role of family, and varied working conditions, including night shifts specifically for female nurses . however, the low enrolment rates have been addressed inequitably by the ministry of education (moe) by establishing enrolment in nursing programs that are open-access for students who were rejected from other health professions due to a low gpa. consequently, the graduation of competent nurses from saudi universities is doubtful. as the moh is a leading government agency, its responsibility is to regulate, plan, finance, and manage the healthcare sector via the council of health services . a royal decree in established the council of health services, which was headed by the moh. the council includes private health sectors and representatives from other governmental sectors. therefore, according to almalki, fitzgerald, and clark , the moh is reflected as a national health service (nhs) for the overall population. however, according to alasmari , no substantial improvement has been made in terms of these platforms and initiatives. significant delays in decisions, less innovative ideas, and resistance to change from the front-line level were led by such a centralized system where the majority of the decisions were made by a small chain of stakeholders , . this prevented the introduction of new concepts and methods to improve the provision of health care in moh hospitals and other private hospitals. moreover, during the last decade, the moh has become less centralized in order to manage healthcare services by operating independent health care clusters with autonomous budgets. nonetheless, there are still many decisions-such as regulation, legislation, planning, and investment-that are controlled by the top-level management of the moh . in addition, although the hospital managers and regional directors of health services have greater supervisory roles and responsibilities, they were left with minimal authority. most importantly, shared governance was identified by nursing professionals as a fundamental determinant of excellence in the nursing profession; thus, it is clear that conventional centralized management does not collaborate with them in order to attract and retain their strategies , . however, most obstacles have been formed due to the hierarchical structures of decision-making, which include employee empowerment and autonomy, that hinder quality of care and develop a lack of trust between employees and managers . at the national level in saudi arabia, there is no nursing council or professional body with established responsibilities and accountabilities for governing nursing practice and providing professional autonomy such as a nursing code of ethics and nursing practice . in this context, at the moh, the general administration of nursing (gaon) is responsible for assorted roles, scopes, and responsibilities for nurses . it also establishes regulations and legislation; therefore, it is a professional institution that oversees the entire nursing community. the scope of nursing practice is defined as the range of roles, functions, responsibilities, and activities that qualified registered nurses are authorized to perform . it reflects all the roles and activities undertaken by registered nurses to address the full range of human experiences and responses to health and illness. it is well-founded to state that the absence of a clear scope in nursing practice increases the workload on nurses and allows the wastage of significant amounts of time on activities that do not enhance patient care, such as housekeeping and secretarial tasks. in recent years, the nursing board has begun focusing on standardizing nursing practice in schs, but the scope of nursing practice has not yet been formalized (al-dossary, ) . therefore, a major challenge has been presented by the restrictions on enacted scope of practice in managing nursing services to maximize the utilization of nurses' skill sets. nevertheless, it must be noted that regardless of a clear standard scope of nursing practice, nurse educators will still experience several issues in clinical practice, and there will be challenges in developing staff educational plans. according to alsufyani , adequate understanding about the policy development process is required while studying policy-making in health care systems to highlight its impact on the framed health objectives. in addition, the process of policy development needs to be negotiable between stakeholders. nurses in healthcare settings, the moh, magnet hospitals, nursing professionals, midwives, nurse educators, practitioners, nursing managers, health accreditation institutions, sponsors as well as representatives from the saudi parliament, other government agencies and private sectors are considered primary stakeholders. visitors, clients, patients, families of patients, families of nurses and midwives, and families of nursing managers are considered secondary stakeholders as are citizens living in saudi arabia who will benefit from having and supporting this policy that augments the level of quality care.  option is to do nothing or stay in the same condition, which means that no changes will be made on the existing policy.  option is to make an incremental change on the existing policy to make it applicable to transform nursing standards and direct it based on the saudi vision.  option is to make a comprehensive and significant change, or derive a new policy from scratch based on the saudi vision. after listing three policy options aiming to facilitate nursing transformation in saudi arabia, it is necessary to narrow down the options to identify the most applicable policy option for politicians and decision-makers by establishing evaluation criteria. a total of five features were considered while comparing the policy alternatives including, social acceptability, political feasibility, fairness, cost, and contribution. the selection of these features was based on the appropriateness in conducting health policy analysis for turning ideas into actions , . amongst these features, the contribution of policy is the most essential feature to achieve the preferred objectives, specifically to transform nursing standards and practices. other important features include the cost of applying changes and political feasibility. furthermore, fairness in distribution of advantages is also essential. lastly, social acceptability is the feature that defines, based on evidence, the extent to which the proposed change becomes acceptable and popular among primary and secondary stakeholders. option restricts making changes or prefers to continue functioning with the current strategies and policies. although, this option is politically feasible with the same cost, it contradicts the saudi arabian vision regarding retaining and empowering nurses. meanwhile, the pressure on nursing staff will be the same as observed in recent cases; thus, it is an inequitable option. option introduces an incremental change to the existing policy. this will accomplish the saudi vision. in addition, it will be politically and economically feasible. furthermore, it will be socially accepted as it is designed to enhance the quality of healthcare. option indicates a comprehensive change or the changing of the policy from scratch. this entails the removal of the existing policy and the establishment of a new policy. although this option will accomplish the saudi vision, it will be politically and economically infeasible as it includes major changes. however, it will be considered fair by the stakeholders and socially accepted. as shown in table , the recommended option for making policy changes is option . the changes made in the policy as per this option will ensure that the saudi vision remains active and focused on nursing demands. further, option will help hospitals that have magnet recognition in their strategic plans as the loopholes in the nursing work environment can be distinguished when nurses possess a high satisfaction level, low turnover rate retention, healthy organizational climate, educational development at every career stage, and autonomous nursing care-which will be accomplished using option . [insert table here] the chronic shortage in nursing with respect to facilities and technologies has been further exacerbated by the rapid growth in the saudi population, healthcare systems, and changing healthcare needs. in terms of nursing manpower, stability and retention can be addressed with benefits like opportunities for administrative and promotion tasks, reduced workload, flexible schedules, and bonuses . for female nurses, the most useful aspect could be the introduction of flexible working hours and reduction in working hours, as % of the nursing workforce is female . in addition, nursing colleges and the moh can collaborate to start enrolment programs in nursing colleges and ensure employment after graduation. this marketing plan may attract high school students . thus, the critical issue of nursing shortage can be addressed through nursing practice, research, and education. there is a need for establishing a national benchmark database in existing magnet hospitals with the current nursing practice to compare clinical, organizational, and nursing outcomes with quality indicators . it appears timely for nursing management to evaluate the effect of the magnet recognition program-in which workplace environments, nurse satisfaction and shortage, and patient care quality and safety are evaluated-on the elected hospitals as well as demonstrate whether it can assist in reducing the professional constraints associated with autonomy, retention, and nursing shortage , . moreover, it has been observed that the nursing shortage can be improved by magnet hospitals with the provision of opportunities that affect the healthcare structure and enhance professional relationships . different hospitals have used the magnet recognition program throughout cultural, political, economic, and clinical settings . thereby, the existence of two magnet hospitals can give nursing managers the opportunity to identify the effects of magnet designation on patient outcomes and nursing practice in saudi arabia. it has been observed that specific changes are required to mitigate the acute shortage of nurses with respect to nursing education. in this regard, increasing the number of nursing scholarships and programs can address the nursing shortage. further, it is a significant responsibility of nurse educators to enhance the attractiveness and good reputation of nursing as a profession, and to meet the demands of the country in order to overcome the burden of the shortage. in addition, the assurance of a highquality curriculum should be the priority of saudi nursing colleges. they should also adopt problembased learning and self-directed learning approaches, and remove the traditional spoon-feeding teaching strategies . on the other hand, nurse leaders and educators should develop campaigns to correct inaccurate stereotypes and long-standing myths, emphasizing the significance of nurses' responsibilities on the interdisciplinary healthcare team, and consequently, enhancing the image of the nursing profession. such campaigns can increase public knowledge and awareness of the nursing profession , . there is a need to develop national guidelines for the scope of nursing. a well-defined scope of nursing practice explains general nursing functions, work-related procedures with other healthcare professionals, and tasks and responsibilities either collaboratively or independently. in addition, it is mandatory to elect and manage adequate restrictions in nurse-client relationships to facilitate therapeutic and safe practice. however, these boundaries further should account for different cultures with varied understanding and anticipations of boundaries and relationships. moreover, the nursing profession can benefit from implementing successful international examples in the saudi arabian healthcare system to improve this situation. for instance, the nursing and midwifery board in australia, the nursing midwifery council (nmc), and the american nurses association (ana) in the united states all provide guidelines and standards of education or codes, training, and practice in their respective countries. these organizations assist in protecting the public by assuring ethical and safe nursing practices and ensuring that nurses are adequately educated and trained for their roles. thus, schs is required to draw from the saudi arabia vision to imitate these international models by establishing an autonomous regulatory council or nursing body and formulating a clear scope of nursing practice based on nurses᾿ knowledge, skills, and judgments. however, it is worth noting that varied implications might be derived from this policy evaluation for nursing education, policymakers, and administration of the saudi nursing profession and the mission towards which it is inclined with respect to the saudi vision. the saudi vision calls for unifying the efforts of nursing leaders, educators, and practitioners toward nursing transformation. nursing transformation requires improving the quality of delivered care, a stronger education foundation, establishing an autonomous regulatory council, formulating a clear scope of nursing practice based on nurses᾿ knowledge and skills, and reducing professional constraints and centralization of the management. the core focus of current policy assessment is on the accomplishment of nursing transformation. in this context, nursing policies and strategies must be continuously monitored for ensuring its consistency with nursing transformation. who. state of the world᾿s nursing : investing in education, jobs and leadership the saudi arabian vision and the nursing profession: the way forward world health organization pharmacoeconomic analysis in saudi arabia: an overdue agenda item for action strategies to address the nursing shortage in saudi arabia clinical decision-making among new graduate nurses attending residency programs in saudi arabia factors influencing the quality of nursing care in an intensive care unit in saudi arabia the nursing profession in saudi arabia: an overview the world bank. nurses and midwives (per , people) -saudi arabia health care in gulf cooperation council countries: a review of challenges and opportunities an overview of nursing in saudi arabia saudi community perception of nursing as a profession health care system in saudi arabia: an overview barriers to nurse-patient communication in saudi arabia: an integrative review organizational climate for innovation and organizational performance: the mediating effect of innovative work behavior association between organizational climate and head nurses' administrative creativity yes, we can and did: engaging and empowering nurses through shared governance in a rural health care setting professional governance: another new concept? the future of nursing magnet® designation in saudi arabia: bridging cultures for nursing excellence advancing nursing practice: the emergence of the role of advanced practice nurse in saudi arabia nursing situation in saudi arabia. riyadh: saudi nursing board, saudi commission for health specialties legal and ethical issues in nursing nurses' everyday activities in hospital care role of theory and research in policy development in health care system conducting health policy analysis in primary care research: turning clinical ideas into action health policy analysis: a simple tool for policy makers the profile of saudi nursing workforce: a cross-sectional study perceptions of the community toward the nursing profession and its impact on the local nursing workforce shortage in riyadh understanding the role of the professional practice environment on quality of care in magnet® and non-magnet hospitals nurse and resident satisfaction in magnet long-term care organizations: do high involvement approaches matter? structural empowerment, magnet hospital characteristics, and patient safety culture: making the link professional governance: another new concept? the international magnet® journey competence of nurses relating self-directed learning in saudi arabia: a meta-analysis strategies of improving the nursing practice in saudi arabia 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 committee on zoonoses viral zoonosis: a comprehensive review zoonotic disease programs for enhancing global health security risk factors for human disease emergence anthropogenic environmental change and the emergence of infectious diseases in wildlife host range and emerging and reemerging pathogens emerging of new viral zoonoses emerging pathogens: the epidemiology and evolution of species jumps global trends in emerging infectious diseases perspectives on emerging zoonotic disease research and capacity building in canada. can emerging zoonotic diseases: can it be the case of bioterrorism zoonotic diseases and one health approach world health organization. zoonoses and veterinary public health (vph) prevalence and control of zoonotic diseases: collaboration between public health workers and veterinarians in burkina faso initial identification and characterization of an emerging zoonotic influenza virus prior to pandemic spread emerging infections: microbial threats to health in the united states. washington. in infectious disease surveillance animal-associated opportunistic infections among persons infected with the human immunodeficiency virus emerging foodborne diseases: an evolving public health challenge clinical practice and public health control zoonoses in the arabian peninsula trend of diseases among iranian pilgrims during five consecutive years based on a syndromic surveillance system in hajj reimagining the hajj travel epidemiology: the saudi perspective food poisoning in saudi arabia, potential for prevention arab news: one million animals sacrificed over three days arab news: vets to oversee slaughter of over m animals during hajj a puppy with toxocara canis in pets shop from saudi arabia zoonotic balantidiasis in camel from saudi arabia. sch. acad having domesticated animals at home on the rise division of vector-borne infectious disease isolation of a novel coronavirus from a man with pneumonia in saudi arabia rabies in camels at qassim region of central saudi arabia rabies in saudi arabia: a need for epidemiological data years of rabies vaccination with rabipur: a summary of clinical data and global experience global, regional, and national age-sex specific all-cause and cause-specific mortality for causes of death, - : a systematic analysis for the global burden of disease study imported human rabies cases worldwide first confirmed case of human rabies in saudi arabia estimating the global burden of endemic canine rabies re-evaluating the burden of rabies in africa and asia rabies among animals in saudi arabia report on the first consultation on wildlife rabies in the arabian peninsula prevalence of comorbidities in the middle east respiratory syndrome coronavirus (mers-cov): a systematic review and meta-analysis mers coronavirus has probably been present in bats for many years, research shows middle east respiratory syndrome coronavirus in bats, saudi arabia middle east respiratory syndrome coronavirus: another zoonotic betacoronavirus causing sars-like disease first confirmed case of middle east respiratory syndrome coronavirus infection in the kingdom of bahrain: in a saudi gentleman after cardiac bypass surgery middle east respiratory syndrome coronavirus infection in dromedary camels in saudi arabia infection control and mers-cov in health-care workers human infection with mers coronavirus after exposure to infected camels, saudi arabia emerging viral diseases: why we need to worry about bats, camels, and airplanes evidence for zoonotic origins of middle east respiratory syndrome coronavirus identification of diverse viruses in upper respiratory samples in dromedary camels from united arab emirates occurrence of the middle east respiratory syndrome coronavirus (mers-cov) across the gulf corporation council countries: four years update middle east respiratory syndrome coronavirus: a review of the current situation in the world risk factors for severity and mortality in patients with mers-cov: analysis of publicly available data from saudi arabia middle east respiratory syndrome coronavirus in medinah city, saudi arabia: demographic, clinical and survival data treatment outcomes for patients with middle eastern respiratory syndrome coronavirus (mers cov) infection at a coronavirus referral center in the kingdom of saudi arabia the predictors of -and -day mortality in mers-cov patients east respiratory syndrome coronavirus-mers-cov|dynamed middle east respiratory syndrome coronavirus: current knowledge and future considerations emerging and reemerging diseases in the world health organization (who) eastern mediterranean region-progress, challenges, and who initiatives. front. public health influenza research in the eastern mediterranean region: the current state and the way forward. influenza other respir swine influenza a (h n ) infection in two children-southern california avian influenza a viruses: evolution and zoonotic infection influenza research in the eastern mediterranean region: a review pandemic influenza a (h n ) in saudi arabia: description of the first one hundred cases highly pathogenic avian influenza (h n hpai) spread in the middle east: risk assessment stirring up "swine flu" hysteria human infection with highly pathogenic h n influenza virus epidemiology, ecology and gene pool of influenza a virus in egypt: will egypt be the epicenter of the next influenza pandemic? virulence susceptibility of influenza viruses circulating in western saudi arabia to neuraminidase inhibitors pigs, poultry, and pandemic influenza: how zoonotic pathogens threaten human health an overview of the epidemic of highly pathogenic h n avian influenza virus in egypt: epidemiology and control challenges possible avian influenza (h n ) from migratory bird characteristics of patients with oseltamivir-resistant pandemic (h n ) , united states continued emergence and changing epidemiology of oseltamivir-resistant influenza a(h n ) virus effectiveness of neuraminidase inhibitors in reducing mortality in patients admitted to hospital with influenza a h n pdm virus infection: a meta-analysis of individual participant data recent developments in bioinformatics analyses of influenza a virus surface glycoproteins and their biological relevance dual resistance to adamantanes and oseltamivir among seasonal influenza a (h n ) viruses: - a comprehensive review of common bacterial, parasitic and viral zoonoses at the human-animal interface in egypt demographic distribution and transmission potential of influenza a and pandemic influenza a h n in pilgrims respiratory viruses and bacteria among pilgrims during the acceptance of h n vaccine among healthcare workers at primary healthcare centers in abha avian flu hits saudi arabia with two new cases transmission of avian influenza virus (h n ) to dogs acute bronchointerstitial pneumonia in two indoor cats exposed to the h n influenza virus influenza a pandemic (h n ) virus infection in domestic cat lung infection and severe anemia secondary to balantidiasis in hamadryas baboons isolation of a flavivirus related to the tick-borne encephalitis complex from human cases in saudi arabia alkhumra, not alkhurma, is the correct name of the new hemorrhagic fever flavivirus identified in saudi arabia propagation and titration of alkhumra hemorrhagic fever virus in the brains of newborn wistar rats virus taxonomy: classification and nomenclature of viruses: ninth report of the international committee on taxonomy of viruses alkhurma hemorrhagic fever virus alkhumra virus infection, a new viral hemorrhagic fever in saudi arabia alkhurma hemorrhagic fever virus in ornithodoros savignyi ticks kyasanur forest disease virus alkhurma subtype in ticks, najran province, saudi arabia the alkhurma virus (family flaviviridae, genus flavivirus): an emerging pathogen responsible for hemorrhage fever in the middle east complete coding sequence of the alkhurma virus, a tick-borne flavivirus causing severe hemorrhagic fever in humans in saudi arabia low diversity of alkhurma hemorrhagic fever virus, saudi arabia is the epidemiology of alkhurma hemorrhagic fever changing: a three-year overview in saudi arabia kyasanur forest disease virus infection in mice is associated with higher morbidity and mortality than infection with the closely related alkhurma hemorrhagic fever virus a preliminary report on cchf in turkey world health organization. crimean-congo haemorrhagic fever crimean-congo haemorrhagic fever: an overview antigenic similarity between the virus causing crimean hemorrhagic fever and congo virus recent progress in the treatment of crimean-congo hemorrhagic fever and future perspectives crimean-congo hemorrhagic fever: history, epidemiology, pathogenesis, clinical syndrome and genetic diversity crimean-congo hemorrhagic fever virus glycoprotein proteolytic processing by subtilase ski- crimean-congo hemorrhagic fever virus fields virology results of a preliminary seroepidemiological survey for crimean-congo hemorrhagic fever virus in egypt crimean-congo haemorrhagic fever virus infection in the western province of saudi arabia detection of crimean-congo haemorrhagic fever virus antibodies in humans and imported livestock in saudi arabia outbreak of crimean-congo haemorrhagic fever in pakistan climate niches of tick species in the mediterranean region: modeling of occurrence data, distributional constraints, and impact of climate change seroprevalence of alkhurma and other hemorrhagic fever viruses, saudi arabia annual report department of agriculture enzootic hepatitis or rift valley fever. an undescribed virus disease of sheep cattle and man from east africa has rift valley fever virus evolved with increasing severity in human populations in east africa? ecology and habitat characterization of mosquitoes in saudi arabia interactions between mosquito larvae and species that share the same trophic level species interactions among larval mosquitoes: context dependence across habitat gradients distribution and ecology of the mosquito fauna in the southwestern saudi arabia prevalence and distribution of anopheline mosquitoes in malaria endemic areas of asir region, saudi arabia studies of identification and population dynamics of anopheline mosquitoes from jeddah province of saudi arabia mosquito fauna (diptera: culicidae) and seasonal activity in makka al mukarramah region, saudi arabia distribution and seasonal activity of mosquitoes in al madinah al munwwrah, saudi arabia prevalence and seasonal distribution of dengue mosquito aedes aegypti (diptera: culicidae) in al-madinah al-munawara, saudi arabia breeding habitats characterization of anopheles mosquito (diptera: culicidae) in najran province, saudi arabia larval habitat, ecology, seasonal abundance and vectorial role in malaria transmission of anopheles arabiensis in jazan region of saudi arabia household survey of containerbreeding mosquitoes and climatic factors influencing the prevalence of aedes aegypti (diptera: culicidae) in makkah city, saudi arabia. asian pac sindbis virus isolations from saudi arabian mosquitoes mosquito vectors survey in the al-ahsaa district of eastern saudi arabia seasonal activity of some haematophagous insects in the riyadh region, saudi arabia distribution of habitats of mosquito larvae (diptera: culicidae) in riyadh region, saudi arabia the mosquitoes of arabia vector bionomics in the epidemiology and control of malaria, part i, the who african region and the southern who eastern mediterranean region, section iii: south-western arabia isolation and genetic characterization of rift valley fever virus from aedes vexans arabiensis, kingdom of saudi arabia integrated vector management: strategic framework for the eastern. the mediterranean region - ; the who regional office for the eastern mediterranean: cairo rift valley fever virus (bunyaviridae: phlebovirus): an update on pathogenesis, molecular epidemiology, vectors, diagnostics and prevention population genetics of two key mosquito vectors of rift valley fever virus reveals new insights into the changing disease outbreak patterns in kenya climatic and geographic influences on arboviral infections and vectors observations on the epidemiology of rift valley fever in kenya isolation of arboviruses in kenya rift valley fever virus activity in east africa in rift valley fever in southwestern saudi arabia: a seroepidemiological study seven years after the outbreak of complete genome analysis of ecologically and biologically diverse rift valley fever virus strains reveals widespread virus movement and low genetic diversity due to recent common ancestry genetic analysis of viruses associated with emergence of rift valley fever in saudi arabia and yemen rift valley fever: an uninvited zoonosis in the arabian peninsula relevance of rift valley fever to public health in the european union camelid infectious disorders world health organization hemorrhagic fever task force. an outbreak of rift valley fever in northeastern kenya, - the epidemic of rift valley fever in saudi arabia: mosquito vector studies emergence of rift valley fever genetic reassortment of rift valley fever in nature first record of aedes (stegomyia) unilineatus in the kingdom of saudi arabia a review of mosquitoes associated with rift valley fever virus in madagascar rift valley fever in kenya: history of epizootics and identification of vulnerable districts spatial and temporal pattern of rift valley fever outbreaks in tanzania camel milk-associated infection risk perception and knowledge in french hajj pilgrims. vector borne zoonotic dis first field evidence for natural vertical transmission of west nile virus in culex univittatus complex mosquitoes from rift valley province rift valley fever and a new paradigm of research and development for zoonotic disease control the epidemiology of dengue fever in saudi arabia: a systematic review aedes albopictus, an arbovirus vector: from the darkness to the light the global distribution and burden of dengue antigenic relationships between flaviviruses as determined by cross-neutralization tests with polyclonal antisera dengue hemorrhagic fever virus in saudi arabia: a review. vect. borne zoonotic dis update on the global spread of dengue virologic and serologic surveillance for dengue fever in jeddah, saudi arabia, - clinical profile and outcome of hospitalized patients during first outbreak of dengue in makkah, saudi arabia department of communicable diseases, ministry of health (moh) saudi arabia ministry of health: riyadh, saudi arabia phylogeny of dengue viruses circulating in jeddah reconstructing historical changes in the force of infection of dengue fever in singapore: implications for surveillance and control dengue fever clinical features of consecutive patients admitted to a tertiary care center in saudi arabia characteristics of dengue fever in a large public hospital factors associated with the spread of dengue fever in jeddah governorate, saudi arabia. east mediterr geographical distribution and spatiotemporal patterns of dengue cases in jeddah governorate from an update on the incidence of dengue gaining strength in saudi arabia and current control approaches for its vector mosquito clinico-epidemiological features of dengue fever in saudi arabia. asian pac dengue fever in makkah, kingdom of saudi arabia molecular and seroprevalence of imported dengue virus infection in al-madinah, saudi arabia seroprevalence of dengue virus infection in aseer and jizan regions, southwestern saudi arabia fever cases in jeddah drop by %-saudi gazette west nile virus review of west nile virus circulation and outbreak risk in madagascar: entomological and ornithological perspectives a neurotropic virus isolated from the blood of a native of uganda isolation of west nile virus in israel origin of the west nile virus responsible for an outbreak of encephalitis in the northeastern united states nile encephalitis in israel, : the new york connection west nile virus surveillance in romania le virus du nil occidental culex pipiens: species versus species complex taxonomic history and perspective incidence of west nile virus in al-ahsa, saudi arabia incidence history of west nile virus in africa and middle east spread of west nile virus in iran: a cross-sectional serosurvey in equines seroprevalence of west nile virus in blood donors at hotel dieu de france west nile virus infection in horses in jordan: clinical cases, seroprevalence and risk factors first isolation of west nile virus from a dromedary camel the first serological evidence for rift valley fever infection in the camel, goitered gazelle and anatolian water buffaloes in turkey an outbreak of dermatophytosis in camels (camelus dromedaríus) at qassim region, central of saudi arabia a survey of rift valley fever and associated risk factors among the one-humped camel (camelus dromedaries) in sudan. irish an epizootic of rift valley fever in egypt in genetic evidence for rift valley fever outbreaks in madagascar resulting from virus introductions from the east african mainland rather than enzootic maintenance the role of the world organisation for animal health (oie) to facilitate the international trade in animals and animal products public health pandemic h n of the hajj spatio-temporal pattern of sylvatic rabies in the sultanate of oman introduction and enzootic of a/h n in egypt: virus evolution, pathogenicity and vaccine efficacy ten years on isolation and genetic characterization of a novel . . . a h n virus from a vaccinated meat-turkeys flock in egypt pandemic (h n ) and hajj pilgrims who received predeparture vaccination rabies. cdc health information for international travel balantidium coli infection in hamadryas baboon (papio hymadryas) in saudi arabia: a case report middle east respiratory syndrome coronavirus: risk factors and determinants of primary, household, and nosocomial transmission hepatitis c virus antibody titers associated with cognitive dysfunction in an asymptomatic community-based sample report on influenza a and b viruses: their coinfection in a saudi leukemia patient the role of birds in the ecology of west nile virus in europe and africa phylogenetically distinct middle east respiratory syndrome coronavirus detected in a dromedary calf from a closed dairy herd in dubai with rising seroprevalence with age seroepidemiology for mers coronavirus using microneutralisation and pseudoparticle virus neutralisation assays reveal a high prevalence of antibody in dromedary camels in egypt challenges of drug resistance in the developing world the threat of antimicrobial resistance in developing countries: causes and control strategies 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 and control global perspectives for prevention of infectious diseases associated with mass gatherings health risks at the hajj the challenges of cholera at the hajj pilgrimage meningococcal disease during the hajj and umrah mass gatherings the threat of meningococcal disease during the hajj and umrah mass gatherings: a comprehensive review chief complaints and diagnosis of patients visited by caravan physicians during hajj 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 - event based surveillance of middle east respiratory syndrome coronavirus (mers-cov) in bangladesh among pilgrims and travelers from the middle east: an update for the period - acute respiratory infections among returning hajj pilgrims-jordan acute rhinosinusitis during hajj season : prevalence of bacterial infection and patterns of antimicrobial susceptibility influenza not mers cov among returning hajj and umrah pilgrims with respiratory illness morbidity and mortality amongst indian hajj pilgrims: a -year experience of indian hajj medical mission in mass-gathering medicine influenza virus but not mers coronavirus circulation in iran, - : comparison between pilgrims and general population mass gathering medicine (hajj pilgrimage in saudi arabia): the clinical pattern of pneumonia among pilgrims during hajj etiology of severe community-acquired pneumonia during the hajj-part of the mers-cov surveillance program proportion of adult community-acquired pneumonia cases attributable to streptococcus pneumoniae among hajj pilgrims in treatment and prevention of acute respiratory infections among iranian hajj pilgrims: a -year follow up study and review of the literature trend of diseases among iranian pilgrims during five consecutive years based on a syndromic surveillance system in hajj patterns of diseases and preventive measures among domestic hajjis from central, saudi arabia demographic distribution and transmission potential of influenza a and pandemic influenza a h n in pilgrims molecular dynamics of staphylococcus aureus nasal carriage in hajj pilgrims this -year surveillance survey evidences the high prevalence of respiratory symptoms in french pilgrims cross-sectional survey and surveillance for influenza viruses and mers-cov among egyptian pilgrims returning from hajj during - . influenza other respir viruses respiratory viruses and bacteria among pilgrims during the a cohort study of the impact and acquisition of naspharyngeal carriage of streptococcus pneumoniae during the hajj viral respiratory infections among hajj pilgrims in mass gathering and globalization of respiratory pathogens during the hajj the prevalence and preventive measures of the respiratory illness among malaysian pilgrims in hajj season mers-cov but positive influenza viruses in returning hajj pilgrims, china impact of hajj on the s. pneumoniae carriage among indian pilgrims during -a longitudinal molecular surveillance study causes of mortality for indonesian hajj pilgrims: comparison between routine death certificate and verbal autopsy findings hajjassociated viral respiratory infections: a systematic review a systematic review of emerging respiratory viruses at the hajj and possible coinfection with streptococcus pneumoniae high prevalence of common respiratory viruses and no evidence of middle east respiratory syndrome coronavirus in hajj pilgrims returning to ghana the spectrum of respiratory pathogens among returning hajj pilgrims: myths and reality influenza a and b viruses but not mers-cov in hajj pilgrims estimating potential incidence of mers-cov associated with hajj pilgrims to saudi arabia the hajj pilgrimage and surveillance for middle east respiratory syndrome coronavirus in pilgrims from african countries 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 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 genetic characterization and diversity of circulating influenza a/h n pdm viruses isolated in jeddah, saudi arabia between tuberculosis and mass gatherings-opportunities for defining burden, transmission risk, and the optimal surveillance, prevention, and control measures at the annual hajj pilgrimage undiagnosed active pulmonary tuberculosis among pilgrims during the hajj mass gathering: a prospective cross-sectional study diarrhea at the hajj and umrah an outbreak of gastroenteritis among iranian pilgrims of hajj during occurrence of tropheryma whipplei during diarrhea in hajj pilgrims: a pcr analysis of paired rectal swabs acquisition of enteric pathogens by pilgrims during the hajj pilgrimage: a prospective cohort study enteric infections circulating during hajj seasons pharyngeal carriage rate of neisseria meningitidis before and after the hajj pilgrimage risk factors for acquisition of ctx-m genes in pilgrims during hajj prescribing pattern at community pharmacies in saudi arabia knowledge, attitude and practice (kap) survey concerning antimicrobial use among australian hajj pilgrims this study evidence a high prevalence of antimicrobial resistance bacteria in pilgrims hospitalized in saudi arabia the occurrence of esbl-producing escherichia coli carrying aminoglycoside resistance genes in urinary tract infections in saudi arabia acquisition of extended-spectrum b-lactamases by escherichia coli and klebsiella pneumoniae in gut microbiota of pilgrims during the hajj pilgrimage of acquisition of a high diversity of bacteria during the hajj pilgrimage, including acinetobacter baumannii with blaoxa- and escherichia coli with blandm- carbapenemase genes acquisition of extended-spectrum cephalosporin-and colistin-resistant salmonella enterica subsp. enterica serotype newport by pilgrims during hajj acquisition of mcr- plasmid-mediated colistin resistance in escherichia coli and klebsiella pneumoniae during hajj potential risk for drug resistance globalization at the hajj health conditions for travelers to saudi arabia for the pilgrimage to mecca (hajj) bin saeed aa. carriage of neisseria meningitidis in the hajj and umrah mass gatherings meningococcal serogroup a, c, w, and y serum bactericidal antibody profiles in hajj pilgrims acquisition of meningococcal serogroup w- carriage in turkish hajj pilgrims who had received the quadrivalent meningococcal polysaccharide vaccine neisseria meningitidis nasopharyngeal carriage during the hajj: a cohort study evaluating the need for ciprofloxacin prophylaxis the study is the first one conducted among pilgrims at the grand magal in senegal and shows the frequency of infectious diseases among participants a comprehensive review of the kumbh mela: identifying risks for spread of infectious diseases kumbh mela : healthcare for the millions pattern of morbidity and mortality in karbala hospitals during ashura mass gathering at karbala, iraq preparedness and health risks associated with moulay abdellah amghar moussem public health surveillance at a mass gathering: urs of baba farid mass gathering in aqaba outbreak of salmonellosis associated with consumption of pulled pork at a church festival outbreaks associated to large open air festivals, including music festivals response to a large rotavirus outbreak on south tarawa an outbreak of measles associated with an international dog show in slovenia measles outbreak linked to disney theme parks reaches five states and mexico this study describes the high incidence of meningococcal disease in a large-scale open-air festival summer music and arts festivals as hot spots for measles transmission: experience from england and wales communicable diseases as health risks at mass gatherings other than hajj: what is the evidence? whole-genome sequencing of measles virus genotypes h and d during outbreaks of infection following the olympic winter games reveals viral transmission routes measles virus spread initiated at international mass gatherings in europe olympic and paralympic games: public health surveillance and epidemiology epidemiology of sexually transmitted infections in visitors for the london olympic games: a review of attendees at sexual health services european football championship finals: planning for a health legacy sports injuries and illnesses during the european youth olympic festival sports injuries and illnesses in the sochi olympic winter games dengue transmission during the fifa world cup in brazil multinational outbreak of salmonella enteritidis infection during an international youth ice hockey competition in riga, latvia, preliminary report sports injury and illness incidence in the rio de olympic summer games: a prospective study of athletes from countries zika virus and the rio olympic games no zika cases reported during rio olympics multiple outbreaks threaten the winter olympics. the disease daily non-pharmaceutical interventions for the prevention of rtis during hajj pilgrimage expected immunizations and health protection for hajj and umrah -an overview key: cord- -n m evh authors: binalrimal, sultan; aldrees, abdulmajed; alwehaibi, mohammed; alasmary, mohammed; alshammery, abdulaziz; alhaidri, essam; alqabbaa, lama title: awareness and compliance of dental students and interns toward infection control at riyadh elm university date: - - journal: gms hyg infect control doi: . /dgkh sha: doc_id: cord_uid: n m evh aim: dental students have increasing patient contact during their education and clinical years, putting them at high risk of cross-infection; therefore, the purpose of this study was to determine the level of infection control practices among dental students and interns at riyadh elm university, riyadh, saudi arabia. methods: total of questionnaires were distributed among interns and clinical students at riyadh elm university. the questionnaire comprised items assessing infection control practices, and the data were tabulated and analyzed by spss to produce descriptive statistics. results: three hundred nine questionnaires were answered (response rate %).the implementation of different infection control measures was good to excellent, except for hepatitis b vaccination and wearing eye protection: only % of males and % of females were vaccinated against hbv, and only % of males and % of females always wore protective glasses. conclusion: compared to previous studies, an increased awareness regarding infection control practices among dental students and interns was noticeable. however, greater emphasis on the importance of infection control, especially compliance with hbv vaccination and wearing protective eyewear, is necessary. dental health care workers (dhcw) are at a high risk of cross-infection through occupational exposure, such as needlestick and sharp instrument injuries (nsis), mucocutaneous contamination, bites, conjuctivitis and mechanical trauma. the eyes are at particular risk from floating particles, which are considered serious hazards for dhcw, because they can transmit various microorganisms, e.g., cytomegalovirus, mycobacterium tuberculosis, hepatitis b and hepatitis c viruses (hbv and hcv), herpes simplex virus type , human immunodeficiency virus (hiv), streptococci, transmissible spongiform encephalopathies (including variant cjd), methicillin-resistant staphylococcus aureus (mrsa), and severe acute respiratory syndrome (sars) virus transmitted through direct and indirect contact [ ] , [ ] , [ ] , [ ] , [ ] , [ [ ] , [ ] , [ ] , [ ] , [ ] , [ ] . the majority of infections are subclinical and almost % of all hbv infections are undiagnosed. therefore, dhcw are at risk every day, because at normal working distances, there is no zone of safety for the risk of cross-infection. the danger is enhanced by the fact that some hazardous microorganisms remain in the air for up to minutes after cavity excavation, and the fact that most human microbial pathogens have been isolated from oral secretions [ ], [ ], [ ] , [ ] , [ ] . in , humphrey [ ] described how three dental staff members developed different infections including syphilis, diphtheria and actinomycosis during the treatment of infected patients. the protection of health workers became imperative, especially with the rise of of the aids epidemic in the s [ ] . routine infection control procedures and recommendations have been available since the s, but were neglected and ignored even by highly educated groups. in , the us centers for disease control and prevention (cdc) adopted the term "standard precautions" to generate broader understanding and awareness of prevention and transmission of infection. in , the cdc published "guidelines for infection control in dental health-care settings", which included standard precautions to ensure safe working environments and prevent cross-infection among dhcw and their patients, and in the cdc published "summary of infection prevention practices in dental settings: basic expectations for safe care" [ ] , [ ] , [ ] , [ ] . despite the emphasis that was placed on making dhcw aware of the risk of cross-infection and the recommended practices to control infection transmission, the percentage of dhcw who adhered to those practices was below expectations [ ] , [ ] , [ ] , [ ], [ ] , [ ] , [ ] , [ ] , [ ] , [ ] , [ ] , [ ] , [ ] , [ ] , [ ] , [ ] , [ ] . even at dental schools, dental students did not comply with infection control practices very well [ ] , [ ] , [ ] , [ ] , [ ] , [ ] , [ ] , [ ] , [ ] , [ ] , [ ] , [ ] , [ ] , [ ] , [ ] , [ ] . because dental students have increasing patient contact during their education and clinical years, they are at massive risk of cross-infection. therefore, the aim of this study was to determine the level of compliance with infection control practices among dental students and interns at riyadh elm university, riyadh, saudi arabia. the study was approved by the review board and ethics committee of riyadh elm university. a total of questionnaires were distributed among clinical students and interns at riyadh elm university, riyadh, saudi arabia. the questionnaire was designed to cover different aspects of infection control practices in dental clinics including: . aseptic techniques, . patient screening and evaluation, . personal protection, . instrument sterilization, . immunization against hepatitis b virus, . surface disinfection, and . equipment asepsis. an informed consent was included in the questionnaire design and required to be signed by every participant. the questionnaire comprised items assessing infection control practices among undergraduate dental students and interns at riyadh elm university. out of questionnaires sent, forms were filled out and returned. fortytwo of the respondents were interns ( female and male), while forms were received from both male and female clinical students ( th -year students, th -year students, th -year students). the results obtained from respondents were tabulated and analyzed using the statistical package for the social sciences, version (spss inc. chicago, il usa). results questionnaires were answered by clinical dental students and interns from riyadh elm university. the distribution of respondents from male and female th -, th -, and th -year students and interns is shown in table . the level of implementation of basic applied infection control measures was found to be good to excellent, except for hbv vaccine coverage and wearing protective eyewear. the results showed that only % of males and % of females had hbv vaccination, and only % of males and % of females always wore protective eyewear (table and table ) . a majority of dental students and interns complied well with different infection control measures during the treatment of patients and between patients, but there is still a need to raise their awareness and improve their attitude regarding infection control practices. the infection control practices followed by dental students and interns during the treatment of patients and between patients are shown in table . / gms hygiene and infection control , vol. , issn - table : distribution of respondents in the college to th -, th -, and th -year students and interns both male and female table : level of implementation of basic infection control measures at the university dental school table : level of implementation of basic infection control measures at the university dental school infection control is a dynamic and ever-changing discipline. standard isolation precautions are designed to reduce the risk of acquiring occupational infections from both known and unknown sources in healthcare settings. awareness of and compliance with these recommendations are crucial for the prevention of infections among healthcare workers (hcw), including dental healthcare professionals. the recrudescence of diseases such as hiv, tuberculosis, hepatitis b and c, and other maladies that were on the decline have made it essential that strict sterilization be maintained. the results of this study showed that the implementation of different infection control measures was good to excellent, except for hepatitis b vaccination and wearing eye protection. saudi arabia was one of the hbv-endemic countries with an overall prevalence of . %. the infection was mostly spread through horizontal transmission in early life. over the years, there has been an enormous decrease in hbv incidence in saudi arabia, and the prevalence rate in was found to be . % which places saudi arabia among the countries with the lowest prevalence rate of hbv worldwide [ ] , [ ] , [ ] , [ ] , [ ] , [ ] . unfortunately, previous studies reported that hcw in saudi arabia showed low compliance with hepatitis b vaccination, and it became mandatory to structure educational programs to raise the awareness and enhance health-care workers' compliance with hbv vaccination [ ] , [ ] , [ ] . it is noteworthy that hbv vaccination compliance was also below expectations among hcw in brazil, serbia, libya, ethiopia, china and india [ ], [ ], [ ] , [ ] , [ ] , [ ] , [ ] , [ ] , [ ] . in previous studies investigating dental students' and interns' knowledge of, attitude toward and compliance with hbv vaccination among private and governmental dental schools in saudi arabia, their attitude was positive regarding infection control protocols, but they unfortunately lacked compliance with hbv vaccination; greater emphasis on the importance of immunization and vaccine coverage was needed. in our study population the compliance was greater than that of these other studies [ ] , [ ] , [ ] , [ ] , [ ], [ ] , [ ] , [ ] but still in need of improvement. the results of this study demonstrate a need to further emphasize eye protection. the importance of protective eyewear was found to be in the interest of both dentist and patient due to the hazards associated with aerosols and floating debris. the use of eye protections with side shields, and regular monitoring of its structural integrity, reduces the risk of conjunctivitis, eye damage or even complete loss of vision [ ]. the use of protective eyewear by dental students, interns and dentists in saudi arabia was found to be low in previous studies [ ] , [ ] , [ ] , [ ] , [ ] , [ ] , [ ] , [ ] . in our study population the compliance was greater, but still in need of improvement. in addition, the low compliance with eye protection was reported among dhcw and students in lebanon, morocco, india, and china [ ] , [ ] , [ ] , [ ] , [ ] . it is the ethical obligation of every health care worker to safeguard themselves and their patients from cross-infection. because the community expects zero risk of infection transmission from health care providers, a novel, more effective approach is needed to raise the awareness of the importance of vaccine coverage, protective eyewear, and adherence to infection control protocols. dental students tend to practice infection control measures they acquired during their clinical practice, and they are the future dental professionals who will provide oral healthcare to the population. therefore, it is the responsibility of every academic institution to facilitate an appropriate preclinical immunization program, provide infection control training to protect students and patients from cross-infection, and educate the future healthcare professionals about safe work practices. the results of this study indicated increased awareness among concerned dental students and interns at riyadh elm university towards the implementation of effective infection control measures. despite the increase awareness, more emphasis on the importance of compliance with hbv vaccination and the adherence to protective eyewear is needed. injury and infection in dental clinics: risk factors and prevention knowledge, attitude and practice of dentists towards prophylaxis after exposure to blood and body fluids analysis of risk factors associated to cytomegalovirus infection in dentistry students hepatitis" -prevention and management in dental practice middle east respiratory syndrome and precautions to be taken by dental surgeons awareness and compliance of dental students and interns hepatitis b virus in gizan, saudi arabia knowledge, attitudes and practice of dentists concerning the occupational risks of hepatitis b virus in al jouf province, saudi arabia seroepidemiology of hepatitis b virus infection in saudi arabian children: a baseline survey for mass vaccination against hepatitis b long-term protection of hepatitis b vaccine years after vaccination is there a need to include hiv, hbv and hcv viruses in the saudi premarital screening program on the basis of their prevalence and transmission risk factors? epidemiology of viral hepatitis in saudi arabia: are we off the hook? dental care and spread of hepatitis b virus infection effect of a dental air turbine drill on the bacterial counts in air prevalence of hepatitis b surface antigen in dental personnel notes on three cases of specific infections of the hand in dental surgeons knowledge, attitude, and practice of infection control among dental students in king khalid university, abha aids and infection control in dental practice: dentists' attitudes, knowledge, and behavior guidelines for infection control in dental health-care settings-- summary of infection prevention practices in dental settings: basic expectations for safe care hepatitis b vaccination coverage and knowledge among healthcare workers at a tertiary hospital in jeddah, saudi arabia hepatitis b virus vaccination status and associated factors among health care workers in shashemene zonal town, shashemene, ethiopia: a cross sectional study concerns regarding hepatitis b vaccination and post-vaccination test among brazilian dentists infection control knowledge and practice: a cross-sectional survey on dental laboratories in dental institutes of north india infection control measures in private dental clinics in lebanon infection control mechanisms employed by dental laboratories to prevent infection of their dental technicians/technologists knowledge and attitude of dental health professionals about middle east respiratory syndrome in saudi arabia attitude and behaviours towards recommended vaccinations among healthcare workers. healthcare (basel) knowledge, attitudes and practices regarding methicillin-resistant staphylococcus aureus (mrsa) infection control and nasal mrsa carriage rate among dental health-care professionals knowledge, attitudes and practices surrounding occupational blood-borne pathogen exposure amongst students in two chinese dental schools infection control measures among dental practitioners in a southern state of india: a cross-sectional study seroprevalence of hepatitis b and c virus infections among health students and health care workers in the najran region, southwestern saudi arabia: the need for national guidelines for health students compliance to hepatitis b vaccination and subsequent development of seroprotection among health care workers of a tertiary care center of saudi arabia dental students' reports of occupational exposures to potentially infectious biological material in a brazilian school of dentistry evaluation of the knowledge and attitudes of dental students toward occupational blood exposure accidents at the end of the dental training program occupational exposure of shiraz dental students to patients' blood and body fluid knowledge, attitudes, and practice regarding infection control measures among dental students in central india attitude and awareness of dental students and interns toward infection control measures in prosthodontic clinics attitudes, and practice of infection control among dental students at sana'a university, yemen. j int oral health infection control: knowledge and compliance among saudi undergraduate dental students to what extent do dental students comply with infection control practices? attitude and practice of hepatitis b virus infection among dental students and interns in saudi arabia compliance of saudi dental students with infection control guidelines knowledge and attitudes towards infection control protocols among the students of al-jouf university in saudi arabia medical and dental students' attitude and practice of prevention strategies against hepatitis b virus infection in a nigerian university awareness and implementation of infection control measures in private dental clinics, holy makkah, saudi arabia awareness and compliance of dental students and interns toward infection control at riyadh elm university the authors declare that they have no competing interests. key: cord- -flsaa wx authors: aldohyan, meshal; al-rawashdeh, nedal; sakr, farouk m.; rahman, saeed; alfarhan, ali i.; salam, mahmoud title: the perceived effectiveness of mers-cov educational programs and knowledge transfer among primary healthcare workers: a cross-sectional survey date: - - journal: bmc infect dis doi: . /s - - - sha: doc_id: cord_uid: flsaa wx background: knowledge transfer of middle east respiratory syndrome coronavirus (mers-cov) involves the dissemination of created/acquired information on mers-cov in hospitals, making this information accessible to all healthcare workers (hcws). this study evaluated the perceived effectiveness of mers-cov educational programs and knowledge transfer among primary care hcws at a hospital in saudi arabia that witnessed the largest outbreak of confirmed mers-cov cases in this country. methods: a survey was distributed among primary care hcws at five clinics in saudi arabia in . those with non-direct patient care responsibilities were excluded. their knowledge was evaluated against facts published by mayo clinic foundation, and its percentage mean score (pms) ± standard deviation was calculated. hcws’ perceived effectiveness of educational programs and knowledge transfer was classified as negative or positive. results: sample comprised of hcws, of which % were females and % were males. almost % were ≤ years old, and % had > years of work experience. almost . % were nurses, . % physicians, . % were pharmacists, and . % were technical staff. pms for knowledge was . ± . . the prevalence of negative perceptions towards educational programs was . % and of knowledge transfer was . %. older(> years of age) and more experienced(> years) hcws had the highest pms for knowledge( . ± . ,p = . and . ± . ,p < . respectively). negative perceptions of educational programs ( . ± . ; p < . ) and knowledge transfer ( . ± . ; p = . ) were associated with a lower knowledge pms. males were . [ % confidence interval . – . ] times and . [ . – . ] times more likely to have negative perceptions of educational programs and knowledge transfer (adjusted (adj.)p = . and adj. p = . , respectively). physicians/pharmacists were . [ . – . ] and . [ . – . ] times more likely to have negative perceptions of both outcomes (adj. p = . and adj. p = . , respectively). less experienced hcws were . [ . – . ] times and . [ . – . ] times more likely to exhibit negative perceptions of the two outcomes (adj. p < . each). conclusions: a negative perception of the effectiveness of mers-cov knowledge transfer was associated with poorer knowledge and was more prevalent among male hcws, physicians/pharmacists and less experienced hcws. hospitals should always refer to efficient knowledge sharing and educational strategies that render beneficial outcomes to patients, hcws, and the public community. electronic supplementary material: the online version of this article ( . /s - - - ) contains supplementary material, which is available to authorized users. middle east respiratory syndrome coronavirus (mers-cov) has created an epidemiological and clinical crisis within countries in north africa, europe, asia and the usa but mainly in the middle east (kingdom of saudi arabia) [ ] . it is a viral respiratory illness, initially discovered in and speculated to have originated from camels or bats in saudi arabia, with subsequent spread to humans and across borders [ ] . since , a minimum of laboratory-confirmed cases have been reported in saudi arabia, of which patients have died, have recovered and two were under treatment [ ] . high-risk groups were those in close contact with camels, geriatric persons, pregnant women, healthcare workers (hcws) and those with pre-existing comorbidities [ ] . mers-cov infection ranged from asymptomatic or mild respiratory symptoms to severe acute respiratory disease and even death, which was reported in three to four out of every reported mers-cov cases [ ] . biologic samples of subjects with a suspected mers-cov infection (based on clinical symptoms) and of those exposed to reported mers-cov cases are tested using real-time reverse transcription polymerase chain reaction (rrt-pcr) assays. serology, such as an enzyme-linked immunosorbent assay and immunofluorescence assay, is also used to confirm mers-cov by the presence of antibodies [ ] . in saudi arabia, a series of modifications was applied to the patient pathways while visiting the emergency departments or admitted as in-patients. this included segregating patients during triage based on prioritizing the inflow of patients by their chief complaints, bed availability and screening of flu symptoms/history of exposure. the infrastructure of the medical facility, particularly the ventilation system and isolation capacity of rooms, was subject to changes. some hospital wards and staff (especially nurses) were dedicated specifically to confirmed mers-cov cases to limit the chance of cross-contamination across wards and hcws. the infection prevention and control department (ipcd) at smng-ha, in particular, was on high alert for such mers-cov outbreaks, especially with the evident transmission of viral infections between patients and hcws at smng-ha. crisis management required a rapid implementation of adequate infection prevention, control procedures and case isolation, in addition to collaboration and coordination with local and international consultations. exceptional efforts have been made by the ipcd to apply the latest and most effective means of universal standard precautions throughout the mers-cov crisis. rules and regulations pertinent to infection control and prevention have been revisited and environmental surveillance has been carried out regularly to ensure that all wards are equipped with suitable protection and precautionary gear. numerous seminars, workshops and awareness campaigns have been launched for hcws of all disciplines to boost their knowledge on mers-cov, as well as their morale, to maintain a high-quality, safe and dedicated service for the patients. the latest updates issued on mers-cov from the world health organization (who), the centers for disease control and prevention (cdc), collaborative task forces (local and regional) and researchers have been circulated regularly among all hcws and across all managerial levels. numerous research studies have been conducted and published on the perception, knowledge and attitude of hcws towards mers-cov. it is rare to find a hcw who has not attended an educational program on mers-cov in saudi arabia. dissemination of mers-cov information/updates or knowledge transfer within a healthcare organization is a process in which this information is created, generated or acquired, and then organized and distributed within the system to ensure it is accessible to all hcws. one of the mechanisms of knowledge transfer is personalization whereby knowledge is transferred from one individual to another, while the other is codification where knowledge is converted into products such as documents, images and videos [ ] . the need to transfer efficiently the precautionary regulations and updates about mers-cov to large numbers of hcws necessitates the mechanism of codification [ ] . in addition, knowledge transfer or information sharing was found to be positively associated with job satisfaction [ ] . authors hypothesized that although the dissemination of knowledge and updates on mers-cov among hcws has been given full consideration, these hcws might have reservations on the effectiveness and quality of mers-cov related educational offerings. therefore, there was an emerging need to evaluate the perceived effectiveness of mers-cov educational programs and knowledge transfer from the hcw's perspective, in a setting that witnessed the largest outbreak of confirmed mers-cov cases in saudi arabia. this was a cross-sectional study, based on an anonymous survey in english distributed among hcws at the primary healthcare centers in smng-ha medical centers, in riyadh, saudi arabia, between october and december . the smng-ha is the second-largest healthcare sector in the country, second only to the saudi ministry of health, and provides healthcare services to the community of national guards, their dependents and employees [ ] . the targeted primary healthcare centers were five randomly selected clinics out of clinics that employ physicians, pharmacists, technicians and nurses. these clinics serve a population of , registrants, with a rate of four visits per registrant annually. eligible primary care hcws were targeted as being in frontline contact with potential confirmed cases of mers-cov. those occupying positions of management, education or non-direct patient care were excluded. medical and nursing students were also excluded. this study was ethically approved by the institutional review board at king abdullah international medical research center, king saud bin abdul-aziz university for health sciences, sp- / . the provisioned sample size in this study was calculated based on a reported level of knowledge between . and . % by alkot et al. among hcws in the western region of saudi arabia. assuming an expected level of knowledge of %, with a % confidence limit (z = . ), and a margin of error %, the estimated sample size for this study was . for convenience, all eligible hcws at the targeted setting were invited to participate in this survey, to overcome a % nonresponse rate. the survey was provided in a sealed envelope with a cover letter that described the objectives of the study. the survey was in english language, as the targeted study participants were english literate and the educational offerings provided at the targeted setting were also in english. participants who agreed to enroll in this study hand-signed an agreement statement at the end of an informed consent, with no need for any personal identifier. the data collection tool comprised the characteristics of the hcw, principally gender, age category (years), job position and experience (years) [ ] . the knowledge of hcws was measured using statements based on undisputed facts published in the literature and issued by the mayo foundation for medical education and research in [ ] . correct answers were scored " ", while wrong/don't know answers were scored " ". the percentage mean score (pms) of knowledge was calculated by adding the correct responses of the statements, dividing the score by and multiplying it by (range of score to ). the perceived effectiveness of the mers-cov educational programs was measured using one statement: "prevalence of mers can be reduced by active participation of healthcare workers in the hospital infection control program", while the perception of knowledge transfer was measured by one statement: "any related information about mers should be disseminated among healthcare workers". both statements were rated on a four-point likert scale (strongly disagree, disagree, agree and strongly agree). those who responded by disagree or strongly disagree were classified as having a negative perception, while those who responded agree or strongly agree were classified as having a positive perception. the negative perception rate was calculated by dividing the number of participants who had negative responses over the total number of respondents. in addition, participants were asked about the source of mers-cov information. the survey was piloted on a group of five hcws, and their subjective comments were considered. the internal consistency or reliability (cronbach's alpha) of the knowledge domain measured . (additional file ). data were analyzed using the statistical package for social studies (spss ; ibm corp., new york, ny, usa). hcw characteristics, perceptions (negative vs positive) and incorrect knowledge response statements were presented in terms of frequencies and percentages, while the pms of knowledge was presented as the mean ± standard deviation. missing data were replaced by the average of the total, and outliers were dropped out. pearson's chi-square test was used to test categorical outcomes across hcw characteristics, while a mann-whitney test and a kruskal-wallis test were used to test the non-normally distributed pms of knowledge scores. two binary logistic regression models were constructed to determine the factors significantly associated with negatively perceived effectiveness of mers-cov educational programs and knowledge transfer. due to the small subgroup size of job positions, nurses were grouped with technicians, while pharmacists were grouped with physicians. these two subgroups had job positions comparable in terms of the educational levels, scope of practice and nature of patient care. the adjusted odds ratios [ % confidence interval] were calculated, and statistical significance was set at a value of p < . . initially, surveys were distributed among hcws; participants agreed to enroll and completed the survey (response rate . %). those who did not participate were mainly either off duty or busy with their workload. females constituted . % of the sample, while males comprised . %. almost % were ≤ years old, % were - years old and % were > years old. the majority ( . %) were nurses, followed by physicians ( . %), pharmacists ( . %) and technical staff ( . %). most hcws ( . %) had accumulated > years of work experience, with . % having < years of experience and . % having - years (table ) . overall, . % of respondents claimed that their main source of information was the internet, while . % reported more than one source, including research studies, books, media and others. the pms of knowledge score was . ± . . the most common incorrect response to the statements ( . %) was that for "incubation time for virus", followed by . % with an incorrect response to the statement that "antibiotics are the first-line treatment for the management of mers-cov". other incorrect responses to statements are listed in chronological order in table . overall, . % of participants reported a negative perceived effectiveness of mers-cov educational programs, while . % had a negative perception of knowledge transfer. with regard to the perceived effectiveness of mers-cov educational programs, male hcws had significantly a more negative perception than female hcws (n = , . %, vs n = , . %, respectively; p < . ). pharmacists (n = , . %) and physicians (n = , . %) reported more negative perceptions than technical staff (n = , . %) and nurses (n = , . %) (p = . ). hcws with work experience of < years had the most negative perceptions in comparison with the other groups (p = . ). a number of factors were associated with a negative perception of knowledge transfer of mers-cov information. male hcws had a greater negative perception than females (n = , . %, vs n = , . %, respectively; p < . ). physicians (n = , . %) and pharmacists (n = , . %) had more negative perceptions of knowledge transfer in comparison with technical staff (n = , . %) and nurses (n = , . %) (p < . ). junior hcws with work experience of < years ( . %) had the highest rate of negative perception of knowledge transfer (p < . ) ( table ) . hcws > years old (pms . ± . ) had the highest knowledge scores in comparison with the other age groups (p = . ). more experienced hcws (> years) also had the highest knowledge scores (pms . ± . ; p < . ). those who had a negative perception of the effectiveness of mers-cov educational programs (pms . ± . ) and of knowledge transfer of mers-cov updates (pms . ± . ) both had lower knowledge scores in comparison with the positive-perception group (p < . and p = . , respectively), table . logistic regression analyses showed that male hcws table . mers-cov educational programs at healthcare institutions are a formal and reliable channel to deliver essential knowledge to hcws. for the sake of personal safety, job satisfaction and work morale, hcws should not pass up any opportunity to increase their theoretical knowledge and practical skills. hospital administrators do not necessarily face the challenge of producing new information, as an immense amount of valuable information already exists in the literature. the problem arises from the fact that current knowledge is either poorly structured or inaccessible to hcws [ ] . for example, advanced practice nurses are observed to be "knowledge brokers" in a sense that they act as disseminators of knowledge among the nursing body. furthermore, health educators retrieve different types of evidence, synthesize it in different forms, translate it by evaluation, interpret it and then distribute it among nurses [ ] . health education can improve levels of awareness and perception among hcws towards mers-cov infections [ ] , and these higher levels of knowledge can aid in the control n frequency, % percentage of disease outbreaks [ ] . however, published evidence in saudi arabia has shown that there is limited knowledge on mers-cov (both microbiological and virological aspects) among hcws in southern saudi arabia [ ] . another study also claimed that knowledge about emerging infectious diseases was poor, and that infection control practices were suboptimal and also seemed to be overestimated [ ] . the association between younger age and less experience on one hand and lower knowledge scores on the other was a reasonable finding. similar to literature findings, the knowledge of hcws in this setting was suboptimal and gaps remain that should direct the focus towards the mechanisms and quality of knowledge transfer. dissemination of mers-cov updates using e-mail, the internet, institutional announcements, employee meetings, the media and even personal communications are all methods of knowledge transfer. hcws can experience knowledge transfer both passively, absorbing information unconsciously, and actively. investigators in this study were curious to know how hcws perceived the transfer of knowledge about mers-cov and why this would be of concern to hospital administrators. for instance, knowledge transfer has been adopted with regard to smoking as a health hazard, hiv transmission as a sexual risk and seat belts in motor vehicles as a safety measure. people are exposed almost daily to precautionary advice by a variety of methods but unfortunately still undertake high-risk activities and are exposed to these hazards. this occurs regardless of the duration, frequency and quality of awareness campaigns. therefore, it is an aggravating concern that the repetitive exposure of hcws to mers-cov campaigns might have created some sort of "tolerance". hcws might disremember or take lightly the acquisition of current or new updates about mers-cov precautions due to routine attendance of educational programs or repetitive circulation of e-mails. knowledge and skills must be passed on in a systematic way from expert to novice employees in a way that makes sense [ ] . managers who support work-empowering environments are actually boosting the engagement of participations in terms of knowledge transfer [ ] . in fact, one of the key elements in seeking accreditation or managing crises such as mers-cov is knowledge communication, in the sense that effective communication ensures a purposeful exchange of information, thus allowing a more thorough understanding of the outbreak [ , ] . interactive workshops remain highly recommended for the sharing and transferring of knowledge among hcws. however, one study noted that, although those who attended such workshops valued the expert input and discussions, after few months their sustainability of attendance was lost [ ] . some barriers to mers-cov knowledge transfer could be the inability of hcws to recognize and articulate the instructions, personal opposition or resistance to change, the quality of the communication technologies, the absence of visual representations, language and cultural differences, deficiency in expertise, the work environment, a lack of job incentive/motivation, the organizational culture and others [ , ] . current efforts to manage the mers-cov crisis are directed towards developing educational programs that target both the community and hcws [ ] . a negative perception of mers-cov educational programs in this setting might result in outdated knowledge among hcws, which jeopardizes their compliance with disease precautionary and control measures. a mers-cov task force committee pointed out that the saudi arabian ministry of health has posted updates on mers-cov through videos, posters, handouts, posters and an official website. resilience against mers-cov increases with enriched education and awareness [ ] . a saudi arabian study reported that hcws were unaware of the availability of mers-cov information at their work areas; they did not feel they had sufficient training and were not confident about infection control guidelines. these factors may also contribute to having a negative perception of mers-cov-related educational programs [ ] . one study reported that the interest in following disease updates among hcws improved significantly after the implementation of a mers-cov educational program [ ] . these programs improved the attitude of the hcws towards governmental measures taken regarding the crisis [ ] . hcws often grasp their mers-cov educational information primarily from watching tv reports, or from the internet. a negative perception of knowledge transfer might be due to a pre-existing lack of trust in the media or in websites that might, to some degree, lack scientific credibility in comparison with educational programs provided in healthcare centers [ ] . knowledge itself is complex, and its transfer process within healthcare institutions carries many challenges [ ] . one way to overcome these challenges is to determine the characteristics of hcws who might be more likely to exhibit negative perceptions of knowledge transfer for significant mers-cov updates. in the literature, knowledge transfer has been investigated more frequently in manufacturing industries and firms, or among the public community. it has been seldom evaluated among hcws [ ] , and never in a middle eastern setting or related to a mers-cov outbreak. a crossnational study suggested that organizational culture was a significant influence on the capacity of hcws to engage in knowledge transfer [ ] . a systematic review paper study stated that knowledge transfer could streamline productivity and coordinate the use of resources more efficiently [ ] . this review paper claimed to be the first to review published research focused on the perceptions of hcws about knowledge management [ ] . knowledge management was defined as having an efficient idea or new practice accepted and adopted by an individual or a group through communication channels (successful diffusion of ideas) [ ] . this definition also applies to the dissemination of updated regulations on the outbreak of mers-cov. this information, once absorbed by people, should be sustained for as long as it is useful, and not decay over time [ ] . accordingly, a negative perception of the importance of knowledge transfer could be a warning sign of an interruption in this sustainability of retained information about mers-cov. signs of information decay were evident among hcws in this study, as those who had negative perceptions had lower knowledge scores about mers-cov in comparison with those who had positive perceptions. one of the key goals of knowledge transfer is to educate and train the less experienced and/or the newly hired hcws [ ] . this phase of staff development is crucial yet stressful for novice hcws, who are expected to acquire skills and competencies rapidly to ensure that a safe and quality service flow is maintained at the institution. this explains why hcws with less work experience (< years) had significantly more negative perceptions of knowledge transfer and the perceived effectiveness of mers-cov educational programs. as they gain more work experience, this perception improves as they realize the importance of education not only for their patients but also for their career advancement. the level of knowledge on mers-cov among hcws in primary healthcare clinics in this setting was found to be less than optimal. as the frontline in the battle of disease prevention and control, hcws are expected to be equipped with the relevant theoretical updates about mers-cov. special consideration should be paid to younger and less experienced hcws whose knowledge on mers-cov was moderately low. a negative perception of the knowledge transfer of mers-cov information and educational programs was associated with poorer knowledge. this negative perception was more prevalent among male hcws, physicians/pharmacists and less experienced hcws. this study has been conducted at one setting, yet the struggle against mers-cov has not ended and will continue against future emerging strains of viruses and bacteria causing communicable diseases in other settings too. knowledge is a valuable asset, and its holders within any healthcare institution should be retained and motivated so that they continue to spread their benefit among other hcws. all healthcare institutions should always identify and refer to reliable sources of knowledge. for instance, the center for disease control and prevention is a leading national public health institute and accountable for disseminating up-to-dates on various infectious topics. in saudi arabia, the ministry for public health has designated communication channels to release updates on mers-cov on their websites, through scientific arenas, memorandums and helpdesks. knowledge sharing and management strategies in the healthcare sector can render beneficial outcomes to patients, hcws, the organization and the public community [ ] . in addition to the attendance of seminars or workshops, other methods of knowledge dissemination might involve launching of journal clubs among hcws to discuss updates on mers cov. audiovisuals at hospitals, such as educational videos on tv screens in lobbies or corridors, constantly enlighten hcws. deeper understanding of the negativity in the perception towards the quality or method of knowledge transfer necessitates a qualitative methodological approach, as face to face interviews with hcws aid in determining the underlying reasons and at a more personal level. furthermore, the execution of these strategies needs to be routinely monitored and evaluated so that the transfer of knowledge is time efficient and effective. optimal theoretical knowledge and practical competence are two main indicators of successful knowledge transfer among hcws. last but not least, a number of key points can be noted: as well as their morale, to maintain a high-quality, safe and dedicated service for patients. -the perceived effectiveness of mers-cov educational programs and knowledge transfer among health workers in this high risk setting was evaluated. -primary health workers were expected to be aware of the most recent updates on mers-cov, yet younger and less experienced hcws had moderate knowledge. -a negative perception of the effectiveness of mers-cov knowledge transfer was associated with poorer knowledge, and was more prevalent among male hcws, physicians/pharmacists and less experienced hcws. global summary and risk assessment middle east respiratory syndrome effects of educational program on mers-coronavirus among nurses students at jazan university - an observational, laboratory-based study of outbreaks of middle east respiratory syndrome coronavirus in jeddah and riyadh, kingdom of saudi arabia laboratory testing for middle east respiratory syndrome coronavirus (mers-cov). cdc what's your strategy for managing knowledge? knowledge management research & practice. journal article does perception of knowledge sharing ,transfer and recognition have an impact on job satisfaction? an empirical study in saudi arabia smoking cessation advice: the selfreported attitudes and practice of primary health care physicians in a military community, central saudi arabia predictors of attitude and intention to use knowledge management system among korean nurses what is mers-cov, and what should i do? : mayo clinic implementing knowledge management practices in hospital-in-the-home units the role of advanced practice nurses in knowledge brokering as a means of promoting evidence-based practice among clinical nurses knowledge, attitude, and practice toward mers-cov among primary health-care workers in makkah al-mukarramah: an intervention study knowledge and perception of health practitioners towards mers-cov in hail region, kingdom of saudi arabia knowledge and attitude towards the middle east respiratory syndrome coronavirus among healthcare personnel in the southern region of saudi arabia knowledge, attitudes and behaviours of healthcare workers in the kingdom of saudi arabia to mers coronavirus and other emerging infectious diseases sense making and knowledge transfer: capturing the knowledge and wisdom of nursing leaders nurses' participation in personal knowledge transfer: the role of leader-member exchange (lmx) and structural empowerment knowledge communication: a key to successful crisis management l'accréditation, source de connaissance et d'enrichissement using interactive workshops to prompt knowledge exchange: a realist evaluation of a knowledge to action initiative culture as an issue in knowledge sharing: a means of competitive advantage academic conferences limited understanding change and change management processes: a case study an educational programme for nursing college staff and students during a mers-coronavirus outbreak in saudi arabia questionnaire-based analysis of infection prevention and control in healthcare facilities in saudi arabia in regards to middle east respiratory syndrome middle east respiratory syndrome-related knowledge, preventive behaviours and risk perception among nursing students during outbreak intra-firm knowledge transfer-a qualitative case study of knowledge transfer and its implications in a soft service firm knowledge management practices in healthcare settings: a systematic review the importance of knowledge transfer between specialist and generic services in improving health care: a cross-national study of dementia care in england and the netherlands diffusion of innovations impaired memory retrieval correlates with individual differences in cortisol response but not autonomic response expatriate knowledge transfer, subsidiary absorptive capacity, and subsidiary performance this study was approved and monitored by king abdullah international medical research center, king saud bin abdulaziz university for health sciences, riyadh, saudi arabia. the authors would like to thank the research office and the institutional review board for their tremendous support. none to declare. the datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. all authors conceptualized and designed the study. md, fs, smr and aaf supervised the conduct of the study and data collection. md, smr and aaf undertook the recruitment of subjects and managed the data. fs, smr and aaf were accounted for the quality control. nar and ms provided statistical advice on study design, data analysis and responded to reviewers' comments. all authors drafted the manuscript, and contributed substantially to its revision as submitted and agree to be accountable for all aspects of the work. ethics approval and consent to participate a self-explanatory letter of invitation to participate was presented to each of the participants. all participants had given written informed consents for their participation in the research presented in this manuscript with full knowledge of the possible risks and benefits of participation. participants consented by ticking "agree", indicating their agreement to provide their feedback for this research study. study was approved by the institutional review board of the saudi ministry of national guard health affairs, riyadh, saudi arabia (protocol # sp / ). this study followed the recommendations of the international conference on harmonization for good clinical practice (ich-gcp). 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.author details key: cord- -gphud yx authors: alyami, h. s.; naser, a. y.; dahmash, e. z.; alyami, m. h.; al meanazel, o. t.; al-meanazel, a. t. title: depression and anxiety during coronavirus disease pandemic in saudi arabia: a cross-sectional study date: - - journal: nan doi: . / . . . sha: doc_id: cord_uid: gphud yx background: covid outbreak in was associated with a high rate of depression and anxiety among individuals in the affected countries. the aim of this study is to explore the influence of the covid epidemic on the psychological distress of residents of the kingdom of saudi arabia. methods: a cross sectional study using an online survey was conducted in saudi arabia between th of march and th of april . the patient health questionnaire (phq ) and generalized anxiety disorder- (gad ) were used to assess depression and anxiety. logistic regression analysis was used to identify predictors of depression and anxiety. results: the prevalence of depression and anxiety among the entire study participants was . % and . %, respectively. non-saudi residents, aged years and above, divorced, retired, university students, and those with income ( to , rs) were at higher risk of developing depression. saudi individuals, married, unemployed, and those with high income (> , rs) were at higher risk of developing anxiety. conclusions: there is a wide range of the saudi residents who are at higher risk of mental illness during covid pandemic. policymakers and mental healthcare providers are advised to provide continuous monitoring of the psychological consequences during this pandemic, and provide mental support. wuhan, hubei province, china in december [ ] . in early march , the first case of covid- was confirmed in the kingdom of saudi arabia, and since then, it caused deaths out of , patients who got infected with this disease [ , ] . the causative agent for covid- has been identified as a new rna virus from the beta-coronavirus family; the transmission rate of it is considered high because it transmitted through respiratory droplets and close contact. the world health organization (who) has categorized covid- as a pandemic infection since the respiratory illness caused by the covid- is highly contagious [ ] because of the novelty of the virus, fast spread, and the lack of therapeutic and preventative strategies [ ] . the kingdom of saudi arabia has taken the deadly coronavirus outbreak gravely even before the ministry of health announced the first confirmed covid- case, for example, it announced the temporary suspension of entry to makkah and madinah in february [ ] . after the first confirmed case, the saudi arabian government announced series of extreme measures to control the spread of the virus beginning by panned all transport in and out of the qatif governorate on march , and most recently on april , to announcing a -hour curfew implemented in the major cities with movement restricted to only essential travel between a.m. and p.m. on april [ ] . the extremely proactive measures taken to prevent the spread of the virus could contribute to provoking public fear, anxiety and/or depression, which is usually neglected during crisis and pandemic management [ ] [ ] [ ] [ ] [ ] . covid- has a severe impact on the physical and mental health of the public during the covid- outbreak; therefore, we aimed to assess the mental health burden of citizens and residents inside the kingdom of saudi arabia during covid- pandemic and to identify potential population(s) who might need psychological intervention. a cross-sectional study using an online survey was conducted in saudi arabia between march th and april th , , to explore depression and anxiety among the general population during the covid- pandemic. a convenience sample of eligible participants was invited to participate in the study. the general population was invited to participate in this study through social media (facebook and whatsapp). all participants voluntarily participated in the study and were thus considered exempt from written informed consent. the study aims and objectives were clearly explained at the beginning of the survey. the inclusion criteria were: a) participants aged years and above and living currently in saudi arabia, and b) participants who had no apparent cognitive deficit. participants were excluded if they were: a) below years of age; b) unable to understand the arabic language; and c) unable to participate due to physical or emotional distress. previously validated assessment scales, the patient health questionnaire (phq)- , and generalized anxiety disorder -item (gad- ) were used to assess depression and anxiety among the study participants. these screening instruments were frequently used and validated as brief screening tools among various populations for depression and anxiety [ ] [ ] [ ] [ ] [ ] . also, the following information was collected: participants' demographics (age, gender, income, education level, employment status, and marital status). furthermore, participants were asked whether they were worried about being infected with covid- or transmitting it to family members (yes/no question) and whether they had underlying chronic conditions (yes/no question). the phq- scale is a -questions instrument given to participants to screen for the presence and severity of depression [ , ] . the gad- instrument was used to screen for anxiety [ ] . the phq- and the gad- instruments asked the participants about the degree of applicability of each item (question), using a -point likert scale. participants' responses ranged from to , where means "not at all" and means "nearly every day". the phq- instrument includes items. items are scored from to generating a total score ranging from to . a total score of - indicates minimal depression, - mild depression, - moderate depression, - moderately severe depression, and - severe depression [ ] . the gad- instrument includes items. items are scored from to generating a total score ranging from to . a total score of - indicates mild anxiety, - moderate anxiety, and - severe anxiety [ ] . prevalence rates of depression and anxiety were determined using a cut-off point, as recommended by the authors of the phq- and gad- scale. in this study, depression was defined as a total score of (≥ ) in the phq- instrument, indicating a case with moderately severe or severe depression. anxiety was defined using the gad- instrument with a total score of (≥ ), indicating a case with severe anxiety. the higher the score, the more severe the case identified by any scale. the prevalence rate of depression was estimated by dividing the number of participants who exceeded the borderline score (≥ ) by the total number of participants in the same population. the prevalence rate of anxiety was calculated using the same procedure. the target sample size was estimated based on the who recommendations for the minimal sample size needed for a prevalence study [ ] . using a confidence interval of %, a standard deviation of . , a margin of error of %, the required sample size was participants. descriptive statistics were used to describe participants' demographic characteristics. continuous data were reported as mean ± sd for normally distributed variables and median (interquartile range (iqr)) for nonnormally distributed variables. categorical data were reported as percentages (frequencies). the mann-whitney u test/kruskal-wallis test was used to compare the median scores between different demographic groups. logistic regression was used to estimate odds ratios (ors) with % confidence intervals (cis) for anxiety or . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . depression. logistic regression models were carried out using anxiety or depression scores above the cut-off points highlighted above. a two-sided p< . was considered as statistically significant. the statistical analyses were carried out using spss (version ). a total of , individuals participated in the study. table more than half of them were employed (n= , , . %). around , % (n= ) of the participants reported that they have a history of chronic disease. the majority (n= , , . %) of the participants reported that they were concerned about contracting covid- or transmitting it to family members. when participants were asked if they have identified any problems over the past two weeks, to what extent have these problems prevented them from doing their work, looking after their household affairs or dealing with people, around half of them (n= , , . %) reported that they faced difficulties. the prevalence of depression among the participants was . % (n= ). the proportions of minimal, mild, moderate, moderately severe, and severe depression were . %, . %, . %, . %, and . %, respectively. the prevalence of anxiety among the participants was . % (n= ). the proportions of mild, moderate, and severe anxiety were . %, . %, and . %, respectively. table details the prevalence of depression and anxiety among participants stratified by severity. table presents participant demographics data and their median depression and anxiety scores. depression median score significantly differed across participants from different demographical characteristics (p< . ). anxiety median score significantly differed across participants by nationality, gender, and education level (p< . ). non-saudi resident, females, elderly individuals aged years and above and young individuals aged below years, divorced and single, individuals with low education level, university students, and individuals with low income ( sr and below) tend to have higher depression median scores compared to others. non-saudi residents, females, and individuals with low education levels tend to have higher anxiety median scores compared to others. the logistic regression analysis identified the following group to be at a higher risk of depression: a) unemployed individuals and b) university students. on the other hand, the following groups were at a lower risk of depression: a) saudi resident, b) males, c) married individuals, d) individuals who completed a bachelor degree, and e) individuals with high income ( sr and above). furthermore, logistic regression analysis showed that the following groups were at a higher risk of anxiety: a) unemployed individuals, and b) and . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint university students. on the other hand, the following groups were at a lower risk of anxiety: a) males, b) elderly individuals aged (aged years and above), c) divorced, d) individuals with moderate-income ( , sr to , sr) table . the spread of the covid- presents serious risks in saudi arabia and globally, which has reported , cases and deaths as of the th of may [ ] . saudi arabia has exceptional circumstances as it is a hub for millions of foreign workers and pilgrims from across the globe. in response to the pandemic and to combat the spread of the disease, the government took swift decisions and closed the two holy mosques, suspended travels to the country and closed most businesses and limited individuals' movement. further, the government is also creating a national narrative to encourage citizens' adherence to emergency measures to respond to the pandemic [ ] . therefore, this research aimed at assessing the anxiety and depression among people living in saudi arabia during the covid- outbreak. overall, the findings in this study demonstrated that more than . % of respondents had moderate-to-severe depression, whereas, the prevalence of moderate-to-severe anxiety exceeded %. during stressful conditions such as the case with covid- pandemic, fear and anxiety about the disease can be overwhelming that may cause depression and anxiety among adults and even children [ ] . the sudden shutdown of services and lockdown of people are predisposing to such conditions particularly when dealing with the unpredictable status of the outbreak. the fear of getting the disease and losing loved ones [ ] is another predisposing factor that may result in such a condition. the prevalence rate of moderate-to-severe depression symptoms in this study seems to be considerably higher than that of those reported by the chinese study that included respondents during the covid- outbreak ( . %) whereas comparable rates for anxiety were noted ( . %) [ ] . also, it was observed that results vary according to the sample size and the used assessment tool. where in another nationwide study among chinese people during the pandemic including , participants revealed a psychological distress prevalence rate of % among all respondents. distress symptoms according to the employed assessment tool included depression and anxiety [ ] . the study also revealed that non-saudi residents had significantly higher prevalence rates of depression and anxiety symptoms (p< . ) than saudi individuals. such results aligned with the percentage of infected cases among the two groups, where, the data showed a pattern in terms of who is more likely to become infected with the new coronavirus. recent reports showed that among confirmed cases, saudis account for % of total cases while other nationalities account for %. these results could be attributed to the status of most non-saudis in terms of occupation, and residence status. a substantial number of foreign workers are in the labour force who live in heavily crowded areas that in most of it lack the needed social distancing requirements [ ] . previous studies reported that foreign workers experienced the highest level of distress among all occupations. reasons such as worrying about exposure to coronavirus in public transportation when commuting to and from work, delays in work time, job security, and consequent deprivation of their salary may explain the high-stress level [ ] . such results mandate the government to take and re-enforce specific measures to control the increase of infected cases. . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint depression and anxiety symptoms were more likely to occur in men than in women. such results are in agreement with other studies that investigated depression and anxiety among the saudi arabian population. the results of a study conducted by al-khathami and co-workers ( ) reported that the prevalence of minor mental illness was significantly higher in women ( . %) than men ( . %) (p = . ) ( ) . further, the prevalence rate was high in the younger age group which, is in agreement with our study as a higher score of depression was associated with individuals younger than years. further, the study of wang et al ( ) revealed that the female gender was significantly associated with a greater psychological impact of the covid- outbreak and had higher levels of stress, anxiety, and depression (p < . ) ( ) . several factors can contribute to women's higher depression and anxiety prevalence rates including biological sex differences, culture, diet, female hormonal fluctuations, and education [ ] . sociodemographic variables association with depression and anxiety were assessed using logistic regression analysis which showed that individuals above the age of years suffer from higher depressive symptoms also, those who are single or with lower education level. similar findings were reported by wang et al ( ) that suggested the association of lower education with a greater likelihood of depression during the covid- outbreak. further, our findings provided data that suggested public's levels of anxiety and depression-related symptoms increase among students and unemployment or those with low income. the results were in agreement with previous research that students were more likely to have depression and anxiety during the pandemic [ ] . the onset of the pandemic was in the middle of the academic year, which contributed to students' fear of losing the year or occurrence of delays in their studies, besides the lack of confidence in remote learning. the closure and social distancing are anticipated to sustain for longer periods, and this apparently will have a direct effect on low income and unemployed individuals [ ] , and, therefore. this might put such categories under a higher level of stress that could lead to anxiety and /or depression symptoms. the results of this research emphasized the impact of the covid- pandemic on the mental health of individuals, expressed in depression and anxiety. the findings of this study, in many aspects, were in agreement with those reported during the pandemic in other countries. therefore, a worldwide collaborative effort is required to develop measures that can address mental health during the covid- pandemic and manage it. this study demonstrated several strengths. first, it addressed the prevalence of depression and anxiety within the initial phase of the pandemic and hence will provide valuable information to policymakers that will enable them to make informed decisions and introduce psychological interventions that can minimize psychological untoward effects and mental health status among saudi arabian people. second, the study employed validated tools for the assessment of depression and anxiety that enhanced the reliability of the study. third, it involved a good sample size that was not limited to specific geographical areas in saudi arabia. however, this study has several limitations. first, the study was based on a web-based survey method, then some vulnerable individuals who have no access to the internet and are unfamiliar with online questionnaires were missed. second, due to the sudden occurrence of the outbreak, an individual's anxiety, and depression prevalence before the outbreak could not be pursued. third, the survey was administered at a single period and hence the stability of the responses is unknown. . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint during the initial phase of the covid- pandemic in saudi arabia, more than . % of the respondents had moderate-to-severe depression, and about . % reported moderate-to-severe anxiety. female gender, student status, low income, and education level respondents were associated with a greater psychological impact of the outbreak and higher levels of anxiety, and depression. our findings may enable policymakers to introduce several measures and psychological interventions that can enhance mental health during the covid- pandemic. . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . ethical approval was obtained from the school of life and health sciences at najran university, najran, saudi arabia. as participation of the study was voluntary, the research ethics committee approved consent waiver. not applicable. the data that support the findings of this study are available from the corresponding author upon reasonable request. the authors declare no conflict of interest. no fund was received for this study. ha and an conceived the study, wrote the methods, conducted the formal analysis, and coordinated the study. an, ezd, t.a. osaid, and ha drafted the manuscript with input from all authors. all authors have been involved in drafting the manuscript or revising it critically for important intellectual content. all authors read and approved the final manuscript. . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . , sr and above . . . . *p < . ; **p < . ; ***p < . ; abbreviation: iqr, interquartile range . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint immediate psychological responses and associated factors during the initial stage of the coronavirus disease (covid- ) epidemic among the general population in china novel coronavirus map coronavirus worldwide data who director-general's opening remarks at the media briefing on covid- - coronavirus disease pandemic in the kingdom of saudi arabia: mitigation measures and hospital preparedness saudi arabia temporarily suspends entry of gcc citizens to mecca and medina: foreign ministry coronavirus: saudi arabia imposes -hour curfew in several cities, including riyadh the psychological impact of the covid- epidemic on college students in china. psychiatry research mental health care for medical staff in china during the covid- outbreak. the lancet psychiatry nursing and complex humanitarian emergencies: ebola is more than a disease. nursing outlook generalized anxiety disorder, depressive symptoms and sleep quality during covid- epidemic in china: a web-based cross-sectional survey. medrxiv mental health care for international chinese students affected by the covid- outbreak. the lancet psychiatry accuracy of patient health questionnaire- (phq- ) for screening to detect major depression: individual participant data meta-analysis. bmj usefulness of the patient health questionnaire- for korean medical students. academic psychiatry validity of the brief patient health questionnaire mood scale (phq- ) in the general population. general hospital psychiatry depression: screening and diagnosis validation and standardization of the generalized anxiety disorder screener (gad- ) in the general population assessment of depression severity with the phq- in cancer patients and in the general population. bmc psychiatry the hospital anxiety and depression scale (hads) and the item patient health questionnaire (phq ) as screening instruments for depression in patients with cancer the generalized anxiety disorder screener (gad ) and the anxiety module of the hospital and depression scale (hads a) as screening tools for generalized anxiety disorder among cancer patients guidelines for clinical care ambulatory a brief measure for assessing generalized anxiety disorder: the gad- . archives of internal medicine world health organization. sample size determination in health studies: a practical manual. world health organization coronavirus disease (covid- ) situation report- . available at cdc, . center of disease control-coronavirus disease iranian mental health during the covid- epidemic. asian journal of psychiatry a nationwide survey of psychological distress among chinese people in the covid- epidemic: implications and policy recommendations. general psychiatry ministry of health saudi arabia prevalence of mental illness among saudi adult primary-care patients in central saudi arabia why is depression more prevalent in women? what will be the economic impact of covid- in the us? rough estimates of disease scenarios the authors acknowledged the deanship of scientific research, najran university for funding this work ; key: cord- - w z un authors: ahmed, shahira a.; karanis, panagiotis title: cryptosporidium and cryptosporidiosis: the perspective from the gulf countries date: - - journal: int j environ res public health doi: . /ijerph sha: doc_id: cord_uid: w z un the present review discusses the burden of cryptosporidiosis in the gulf cooperation council (gcc), which is underreported and underestimated. it emphasizes that the cryptosporidium parasite is infecting inhabitants and expatriates in the gulf countries. children under years are a vulnerable group that is particularly affected by this parasitic disease and can act as carriers, who contribute to the epidemiology of the disease most probably via recreational swimming pools. various risk factors for cryptosporidiosis in the gcc countries are present, including expatriates, predisposing populations to the infection. water contamination, imported food, animal contact, and air transmission are also discussed in detail, to address their significant role as a source of infection and, thus, their impact on disease epidemiology in the gulf countries’ populations. cryptosporidiosis is a significant diarrhoeal disease for both people and animals worldwide. several species of the protozoan parasite cryptosporidium can cause this disease [ ] , in which cryptosporidium oocysts have ubiquitous presence in the environment. cryptosporidium oocysts transmission can occur following direct or indirect contact with an infected host usually via the faecal-oral route. person-to-person contact, zoonosis, and the consumption of contaminated food or water are well known mechanisms for faecal-oral transmission [ , ] , with a significant risk of infection from the ingestion of a single oocyst [ ] . when the oocysts enter the gastrointestinal tract, the invasive cryptosporidium causes damage to the small intestinal epithelium. it disrupts the barrier function and absorption capability that leads to mild-to-severe diarrhoea and other abdominal symptoms. in immunocompetent adults, cryptosporidium infection is usually asymptomatic or mild, which is generally self-limiting. currently, cryptosporidium has reported species with more than valid genotypes [ ] . amongst them, species and genotypes have been identified in humans, out of which c. parvum and c. hominis are the most common pathogenic species, causing more than % of infections in humans. c. meleagridis, c. ubiquitum, c. cuniculus, c. muris, and c. andersoni are other pathogenic species that have sporadically emerged in human cases of zoonotic outbreaks, especially when there has been direct contact with infected animals [ ] [ ] [ ] [ ] [ ] . the disease-causing species and their associated subtypes have contributed to a substantial global burden of cryptosporidiosis and play a role in the severity of the disease [ ] . globally, diarrhoeal diseases have killed . million people in . one third of these deaths were children under years, and their highest mortality are from sub-saharan africa (ssa) and south asia. this was because int. j. environ. res. public health , , of challenges (water scarcity, water quality, desertification, and air and marine pollution) that require reconciliation of many conflicting priorities [ , ] . one of the most critical problems that affects public health in the gcc countries is the lack of renewable water resources. infrequent rainfall in the arabian peninsula has led to the overutilization of ground water resources that has consequently affected the qualitative and quantitative of ground water needed for agriculture, industry, and personal consumption [ ] . most of the demand for fresh water in the gcc countries relies on desalination of seawater, which is a process that requires an extensive pre-treatment and conditioning of seawater [ ] . due to this rigorous treatment of seawater, researchers typically do not suspect desalinated drinking water as a source of cryptosporidium contamination; however, it can happen. during the course of the water treatment process, contaminants and beneficial nutrients could be removed and of course some might be added [ ] once stored in tanks or used to fill swimming pools [ , ] . the burden of infectious diarrhoea in the countries of the gcc has been addressed in various reviews on the middle east and north africa (mena) and eastern mediterranean region (emr). infectious diarrhoea has been reported by the united states military after it experienced a significant burden from this disease in the mena campaigns of world war ii [ , ] . traveller's diarrhoea due to ingestion of bacteria, viruses, or protozoa has been reported to affect travellers to saudi arabia [ ] . diarrhoeal infections among mena children pose a significant public health challenge [ ] and has been indicated in many reports affecting children in the gcc countries [ , [ ] [ ] [ ] [ ] [ ] [ ] [ ] . the mortality from diarrhoeal diseases in the gcc countries has also been estimated in a study from the emr. it has been estimated that over , deaths have occurred in due to diarrhoea in the emr. the majority of these deaths ( . %) have occurred in children under years and the dalys/ , ranged from in kuwait to , in somalia [ ] . cryptosporidium has been reported to be the th leading cause among diarrhoeal aetiologies responsible for death in the emr population. approximately . death have resulted in children under years and . death from all age groups due to fatal cryptosporidiosis in the emr area. it has been noted that mainly uae and kuwait have the lowest prevalence-weighted risk for diarrhoeal infection [ ] . the wealth of the gcc countries has attracted many people to seek work opportunities that has notably increased the population in the region and subsequently increased the burden of infectious diseases, particularly gastrointestinal diseases [ , ] . the pattern of the parasitic infection has shifted to reflect this newly mixed population (inhabitants and immigrants), whereas many of these immigrant nationals have dissimilar educational backgrounds, varied eating habits, different religious beliefs and cultural practices [ ] . little is known about the true extent of intestinal parasitic infection, particularly cryptosporidiosis, among the inhabitants of the gcc countries. several studies have reported intestinal parasites infection in immigrant food handlers, labourers, and hospitalized children from this region [ , [ ] [ ] [ ] [ ] [ ] [ ] [ ] . economic migrants seeking employment in the gcc countries (e.g., servants, food handlers, housekeepers, childcare assistant, and labourers) may arrive carrying their parasitic infections with them. therefore, the risk of parasitic infection has been estimated to be higher in some sectors of the communities, especially asymptomatic carriers who are employed in the food industry [ ] . the food industry has been suspected to be the greatest threat in the spread of diarrhoeal aetiologies. the gcc countries import large amounts of food in order to bridge the gap between food production and food consumption. imported food mainly comes from high-risk countries with a known epidemiology of diarrhoeal diseases [ ] . imported leafy greens and other fresh produce are highly suspected to be a vehicle for the transmission of the cryptosporidium infection [ , , ] . the potential for food contamination on and off farms is high since it could be produced or washed with contaminated water. infected food handlers are another common source of cryptosporidium contamination in the food chain imported by the gcc countries [ , ] . studies from countries with low, intermediate, and high resources have identified cryptosporidium as one of the major causes of diarrhoea and childhood malnutrition [ ] . the magnitude and nature of environmental threats might be the link with the incidence of cryptosporidiosis burden and might explain the differences between the previous three categories. in this context, immigrant geographic origin, globalization of food supply to meet the demand of the increased labour force, food and water contamination, climate change, as well as poor hygiene after direct animal contact have all contributed to the annual flux in cryptosporidium transmission and infection rates within the gcc countries [ , ] . in the present review, we aim to discuss the size of the burden of cryptosporidium infection in the gcc countries based on the existing information, and to discuss the risk factors that contribute to the cryptosporidium infection in such a wealthy region. the pubmed, science direct, and scopus databases were searched with no restriction to language or year of publication. to evaluate the burden of cryptosporidium in the gcc population, a clear description of the questions raised with regard to participants, interventions, conditions, outcomes, and study design (picos) was performed. the literature search strategy was limited to title/abstract/keyword using the following mesh terms/key words: (cryptosporidium or cryptosporidiosis or parasite) and (infection or prevalence or incidence or occurrence or burden) and (human or animal or water or food) and (bahrain or kuwait or qatar or saudi arabia or oman or united arab emirates). the screened articles were published between and . some relevant articles that were published in arabic local journals have been retrieved from library genesis scientific articles and egyptian knowledge bank, google scholar, iraqi scientific academic journals, and researchgate. retrieved articles with titles that suggested the topic of cryptosporidium in humans were screened and selected as part of the eligibility for inclusion in the literature review. abstracts from the selected reference titles were reviewed to determine if the selected studies have met the inclusion criteria. review of an entire article was performed based on the selected abstracts that previously met the inclusion criteria. the exclusion criteria consisted of studies on animal cryptosporidiosis or studies that related to foodborne/waterborne cryptosporidiosis as they will later be detailed in the risk factors chapter. the articles that have been published in english or arabic were the only selected languages included in the review. articles in the form of case reports or reviews or conference proceedings were excluded. for each article, the following information was extracted: location of the study, type of residents, cryptosporidium detection method, participants classification, most affected age of participants, symptoms associated with the disease (when available), number of cases, and prevalence of the disease-as reported by the authors or calculated from data presented in the paper (when available). the combined search retrieved studies. a total of studies were retained based on screening of the titles. an additional six studies were added by the screening reference lists from other sources. therefore, studies were subjected to abstract screening. in total, articles were retained for full text analysis and subsequently articles were selected for the analysis of human cryptosporidiosis, from which only of the articles were selected for final analytical inclusion ( figure ). due to incompatibility with the inclusion criteria, articles were excluded. specifically, the exclusion criteria were based on articles that had indistinct data, absence of full text, poor quality citation, reviews, case reports, or reports that included the same results as another paper published by the same author. out of the six gcc countries, five countries have reported human infection from cryptosporidium spp. saudi arabia leads other gcc countries in the reporting of cryptosporidium infection. bahrain has not issued any reports concerning cryptosporidium infection (table , figure ). the allocation of cryptosporidium reports in the gcc countries is presented in figure . the burden of cryptosporidium in the gcc countries is presented in table . molecular genotyping and sub-typing data of cryptosporidium in gulf reports are presented in table . the situation of cryptosporidium in water resources of the gcc countries is summarized in table . information on out of the six gcc countries, five countries have reported human infection from cryptosporidium spp. saudi arabia leads other gcc countries in the reporting of cryptosporidium infection. bahrain has not issued any reports concerning cryptosporidium infection (table , figure ). the cryptosporidium occurrence in animals within the gcc countries is tabulated in table . the results that are indicated in the figure and tables are described below. the six gcc countries are classified as high-income developing countries that share an infection prevention and control program [ ] . other public health programs have been declared successful by the world health organization (who) [ ] . only reports of cryptosporidiosis have been published from of the gcc countries. considering that many of these wealthy countries have the necessary research equipment and facilities, the number of reported articles is considerably low for their capability. this situation indicates an underestimation and underreporting of cryptosporidium infection in the gulf region. saudi arabia has the highest number of reported cryptosporidium infections in humans with a significant p-value < . in comparison to the rest of the gcc countries. saudi arabian reports of cryptosporidium infection have formed half of the total reports number ( / ) cited in the literature that reached an incidental rate of % ( figure , table ). the kingdom of sa is considered to be the largest of the gcc countries with a population of . million people [ ] . it has a well-established public health system and public safety measures that are applied before mass gatherings that attempt to protect pilgrims during the hajj season. gastrointestinal infections during mass gatherings are a major health hazard. therefore, sa authorities routinely provide continuous surveillance for several protozoal, viral, and bacterial pathogens as a part of its measures to protect public health [ ] . the proactive safety measures and awareness of infectious disease has placed saudi arabian authorities higher in the reporting scheme within the gcc countries. even though the saudi government has key planning considerations for emerging diseases alerts based on the who's recommendations, cryptosporidium infections has been reported within the population of makkah before and during the umrah season. it has been observed that the incidental rate of various intestinal parasites has increased by . % among people around the holy masjid during umrah [ ] . overcrowding has been frequently cited as a significant risk factor associated with cryptosporidium infection in other low-and middle-income countries [ ] . the allocation of cryptosporidium reports in the gcc countries is presented in figure . the burden of cryptosporidium in the gcc countries is presented in table . molecular genotyping and sub-typing data of cryptosporidium in gulf reports are presented in table . the situation of cryptosporidium in water resources of the gcc countries is summarized in table . information on the cryptosporidium occurrence in animals within the gcc countries is tabulated in table . the results that are indicated in the figure and tables are described below. the six gcc countries are classified as high-income developing countries that share an infection prevention and control program [ ] . other public health programs have been declared successful by the world health organization (who) [ ] . only reports of cryptosporidiosis have been published from of the gcc countries. considering that many of these wealthy countries have the necessary research equipment and facilities, the number of reported articles is considerably low for their capability. this situation indicates an underestimation and underreporting of cryptosporidium infection in the gulf region. saudi arabia has the highest number of reported cryptosporidium infections in humans with a significant p-value < . in comparison to the rest of the gcc countries. saudi arabian reports of cryptosporidium infection have formed half of the total reports number ( / ) cited in the literature that reached an incidental rate of % ( figure , table ). the kingdom of sa is considered to be the largest of the gcc countries with a population of . million people [ ] . it has a well-established public health system and public safety measures that are applied before mass gatherings that attempt to protect pilgrims during the hajj season. gastrointestinal infections during mass gatherings are a major health hazard. therefore, sa authorities routinely provide continuous surveillance for several protozoal, viral, and bacterial pathogens as a part of its measures to protect public health [ ] . the proactive safety measures and awareness of infectious disease has placed saudi arabian authorities higher in the reporting scheme within the gcc countries. even though the saudi government has key planning considerations for emerging diseases alerts based on the who's recommendations, cryptosporidium infections has been reported within the population of makkah before and during the umrah season. it has been observed that the incidental rate of various intestinal parasites has increased by . % among people around the holy masjid during umrah [ ] . overcrowding has been frequently cited as a significant risk factor associated with cryptosporidium infection in other low-and middle-income countries [ ] . the number of cryptosporidium reports from the other gcc countries (kuwait, uae, qatar, and oman) varied between and reports in the literature search ( figure , table ). kuwait is ranked second after sa for reporting cryptosporidium infections ( reports). in a kuwaiti study that estimated the infectious and parasitic diseases mortality, there has been a steady decline in the number of deaths from infectious and parasitic diseases in kuwait since . this decrease in deaths has dropped from in to in . however, when the researcher compared the death rate from infectious and parasitic diseases between kuwait and selected developed countries, the study showed that, despite considerable improvement, the real rate of infectious and parasitic mortality in kuwait remains very high compared to that in developed countries [ ] . in qatar and uae, the reporting system for cryptosporidium infection can be considered marginal, although they have rich economies indicated by per capita gross national income (gni) [ ] . the few reports that have been published from the gcc countries, with regard to parasitic infections, appear to give a false sense of security that these diarrhoeal parasitic pathogens may not be a serious problem in the region. gcc countries that neglect to screen or report the occurrence of cryptosporidiosis cases could be misinterpreted as having an absence or low prevalence of cryptosporidium in those countries. recent published data have highlighted the importance of monitoring and investigating intestinal parasites after several worldwide cryptosporidium outbreaks. bahrain is the only country in the gcc region that does not have a published record for cryptosporidium infections. in spite of reporting helminths and other protozoa in humans since [ ] , cryptosporidium has not been considered or included in routine investigations of diarrhoeal infections. bahrain has a relatively smaller economy than its oil-rich neighbours in the arab gulf. over the years, bahrain's oil production has deteriorated dramatically, resulting in a high unemployment rate and poverty ( % of citizens), which may explain in part its neglected focus and research implementation of neglected diseases [ , ] . in about % of the reported studies in the gcc countries, cryptosporidium has been linked to gastrointestinal symptoms, particularly diarrhoea in children under years old (table ). in the middle east, % ( volunteers) of military soldiers have reported at least one diarrhoeal episode [ ] . in % of the cases, diarrhoea resulted in a median of days of lost work productivity and a median of days confinement to bed. adverse effects of diarrhoea have caused % of the affected subjects to seek medical attention and subsequent intravenous rehydration from diarrhoeal complications [ ] . in the gcc countries, other categories of adult patients (immunocompromised, umrah people, and expatriates/immigrants) have also reported diarrhoea that had been caused by cryptosporidium infection [ , , , , , , ] . if this is indeed the situation with adult diarrhoeal cases, it would be expected that children under years are more vulnerable to the adverse effects of diarrhoea from cryptosporidium infection. two paediatric case reports as early as have linked cryptosporidium infection to symptoms of severe diarrhoea, vomiting, and low-grade fever in children from kuwait [ ] . over one third of the country's infectious and parasitic deaths were reported as diarrhoeal deaths of infants and young children [ ] . in jeddah, the largest commercial city of saudi arabia, it was identified that . % of school children have reported diarrhoea during the previous month in a study focusing on boys' public schools ( schools) that serve children aged - years. the main risk factor indicated in the analysis of the study was the number of children under the age of five living in the same household. other risk factors associated with an increased risk of diarrhoea that was noted in the study are sewage spillage near the home, no drying for hands after washing, use of reusable cloths to dry dishes, and eating out after school hours [ ] . in uae, a survey of parents with children under years of age have reported that % of parents sought medical care for their children for the treatment of acute gastroenteritis within a three-month period, where % of those children required hospitalization with an average length of stay of . days due to complications of severe diarrhoea [ ] . asymptomatic children with cryptosporidiosis are considered to be carriers and act as important reservoirs for cryptosporidium oocysts in the community [ ] . in the global burden of diseases (gbd), injuries, and risk factors study, cryptosporidium infection was the fifth leading cause of diarrhoeal mortality in children younger than years, causing , deaths in . according to the study, for every episode of cryptosporidial diarrhoea, there was an associated decrease in height-for-age, weight-for-height, and weight-for-age z scores, which translated into an additional . million dalys [ ] . in north africa and the middle east, researchers have distributed the dalys source in children under due to cryptosporidium infection into % wasting, % acute diarrhoea, % underweight, % stunting, and % protein energy malnutrition [ ] . paediatric diarrhoea has significant consequences on productivity and the financial impact on the livelihood of the affected families [ ] . in the gcc countries, there has been a notable economic burden due to diarrhoea in children. for example, the total cost of hospitalization in oman due to paediatric diarrhoea was estimated to be $ /child/ days stay in hospital. for all outpatient and hospital settings in oman, the total cost reached $ . million per year [ ] . in the uae, the average cost for medical care per paediatric diarrhoeal episode has been estimated to be $ [ ] . the lack of comprehensive studies on cryptosporidium infection in paediatric diarrhoeal cases need to be strengthened in the gcc countries to reduce the economic burden associated with diarrhoeal diseases, to provide healthy children without long lasting adverse effects, and to reduce the transmission circle between family members and between families where the child is always the focus of cryptosporidium infection. diagnosis and identification of cryptosporidium infections in the gcc countries varies among the reports. the majority of them are based on the use of staining methods; however, occasionally confirmation of staining is combined with other sensitive methods like immune tests and pcr to make diagnosis ( table ). the diagnostic method of choice for the detection and identification of cryptosporidium usually varies according to the investigator's goal as well as the available facilities and resources to make the diagnosis [ ] . the prevalence of cryptosporidium infection also varies among the gcc countries, with a prevalence ranging between . and . %. the studies that have depended on combined stains and immune tests authors noted a wide range of prevalence between . and . %, while studies that have used pcr methods to confirm cryptosporidium prevalence ranged between . and . %. only one study has reported a high prevalence of % by the authors, who used pcr to analyse previously confirmed positive samples via staining [ ] (table ) . only eight out of studies ( . %) from gcc countries have further processed their isolates by molecular analysis to verify the geno-/subtyping of cryptosporidium spp.. the molecular methods used in these studies varied between arbitrarily primed pcr, qpcr, sequencing, and pcr-rflp, where pcr-rflp was the most commonly used technique to the identify the cryptosporidium spp. and subtype ( table ) . pcr methods are well established techniques that are used to detect cryptosporidium dna in samples with accuracy, sensitivity, and specificity over traditional staining methods. quantitative pcr (qpcr) is known to be the most accurate amongst the pcr methods due to a decreased risk of sample contamination; early reporting of results, particularly during outbreak investigations; and with the detection and quantitation of the target nucleotide sequences down to one or a few copies per samples [ ] . the majority of the gcc studies used pcr-rflp to detect cryptosporidium spp., probably due to the lower costs associated with this highly accurate technique. we have concluded that the studies that used pcr methods had the most realistic prevalence and burden numbers of cryptosporidiosis in the gcc countries ( . - . %). other factors must be considered that can affect the prevalence of cryptosporidium in these studies. for example, differences in method, number and type of diagnostic method used, number of selected samples for the study, target population, aim of the study, state of the population's health, symptomatology, and expertise of investigators. c. parvum, c. hominis, c. meleagridis, and c. muris have been the identified species that infect humans in the gcc countries [ , , , , , , ] . distribution of different cryptosporidium genotypes in human populations can be considered an indication of the differences in infection sources [ ] . c. parvum has been reported to be the dominant species in isolates from the gcc countries. in kuwait, c. parvum has been identified as the predominant causative species of cryptosporidiosis in children [ , ] . in qatar, it was the principal species as well in the qatari children and expatriates [ , ] . saudi arabian children from gizan and maddina were also dominantly infected with c. parvum [ ] . c. parvum is a species that infects a broad range of mammals and is considered one of the major zoonotic disease problems [ ] . its dominance in the gcc countries indicates that there is an animal-to-human transmission, particularly when subtyping outcomes are considered. from subtyping data of cryptosporidium infections in the gcc countries, c. parvum iid has been shown to be the predominant subtype family in most of the gcc countries ( table ). the iid subtype has been referred to as the major zoonotic subtype family in europe, asia, egypt, and australia [ ] [ ] [ ] [ ] [ ] [ ] . its distribution has been associated with the domestication of goats, sheep, calves, horses, donkeys, and takins [ ] . according to qatari and kuwaiti paediatric diarrhoeal studies that have investigated the risk factors associated with cryptosporidium infection, there has been limited, if indeed any, contact with farm animals when investigators were considering the source of initial infection [ , ] . on the other hand, the frequent reporting of the iid subtype family in the gcc countries suggests the potential occurrence of zoonotic transmission of c. parvum. the qatari studies have indicated that there is a predominance of the iid subtype family in its hospitalized children and immigrants, and suggested that cryptosporidium contamination from foodborne transmission or person-to-person contact, but there is no indication that the source of infection could also be from contaminated water or contact to animals [ , ] . none of the qatari studies reported prevalence or occurrence of cryptosporidium spp. in local animals or drinking water. one study from kuwait has indicated that nine of the paediatric cryptosporidiosis cases had direct contact with animals but did not demonstrate any significant association between the risks of infection from those animals [ ] . another study in kuwait has investigated sheep and goat farms and found a predominance of the c. parvum iid subtype family in two-thirds of the infected animals [ ] . in saudi arabia, cryptosporidium has been detected in camels, sheep, and goats, but there has been no further molecular identification of these species and subtypes [ ] . more research is needed in the gulf region to confirm if animal contact is a major source of infection. the prevalence of the cryptosporidium needs to be investigated in the animal population. in addition, the authors of this review have speculated that if the elderly populations were included in the gulf research studies, there may be a significant correlation between the cryptosporidium positive cases and contact with animals, particularly in arab falconers and those who enjoy breeding and riding camels (see details in the next chapter). c. hominis is a species mainly restricted to humans (anthroponotic transmission) despite it has been recently reported in young calves [ ] . it has been reported to be the predominant species in children from makkah, saudi arabia [ ] . other studies have noted its occurrence in a few number of cases from qatari immigrants ( ) and hospitalized children ( ) [ , ] , kuwaiti symptomatic children ( ) [ , ] , and saudi arabian children ( ) [ ] (table ) . person-to-person contact is also a plausible way to contract cryptosporidiosis in the gcc countries; however, it appears to only represent a very small percentage of cases in the available literature. c. meleagridis and c. muris have been the least reported species in the gcc countries. qatar and sa are the only countries that reported these species from their isolates. c. meleagridis has been described within mixed infections of c. parvum in two qatari reports (children and immigrants) [ , ] and as a single species infection in asymptomatic saudi children [ ] , whereas its transmission has not been clarified in any of those studies. c. meleagridis primarily infects birds and mammals and is considered the third most common cause of cryptosporidiosis in humans [ ] , despite it frequently being reported in particular populations of thailand, peru, and japan [ , ] . the qatari cases with c. meleagridis infection seem to be linked to travel to endemic areas or countries, or were infected from people coming from endemic areas or contact with birds, e.g., falcons. a single c. muris case has been reported in one saudi child; however, the conclusions are marginal since the authors reported pcr technical difficulties with processing the c. muris dna. further, this particular isolate was the only species that was withheld from the gel electrophoresis during their pcr-rflp analysis [ ] . zoonotic and anthroponotic transmissions of oocysts are known pathways for cryptosporidium infection in the gulf population. it is essential that gulf governments, public health authorities, and investigators consider publishing more investigations on cryptosporidiosis in animals and symptomatic individuals who have had direct contact with those animals. it would be worthy to combine human and animal investigations in one study for the detection of cryptosporidium that uses molecular analysis to verify the genotype/subtype prevalence in human and animal populations. poor water quality, animal contact, overcrowded living conditions, household diarrhoea, and open defaecation have been identified as significant risk factors for cryptosporidium infection in lowand middle-income countries [ ] . countries that have been identified as "poor income countries" can suffer additional risk factors that double the predisposition for cryptosporidiosis. these risk factors include inadequate water supply, water crises, unclean water, poverty, illiteracy, social unrest, climate change, political conflict, and underdevelopment, which can create dramatic consequences in the poorest members of this population [ ] [ ] [ ] . due to the high-income status of the gcc countries, the risk factors for cryptosporidium infection and other infectious diseases are notably lower than those in the "poor income" category. collectively, the gulf reports have only addressed one major risk factor (expatriates) but neglected to specify other epidemiological factors that may contribute to cryptosporidium infection in the region. the most putative important risk factors for cryptosporidiosis in the gcc countries will be presented in the following sections. the gcc countries are considered the poorest region in the world in its water resources. this is due to their geological location and climate. they are characterized by their arid environment (hot and dry) with irregular and infrequent rainfall, high evaporation rate, and scarcity of renewable water resources [ , ] . arid regions have a higher correlation between available water resources and public health problems [ ] , which can consequently have a negative impact on the social and economic development in the region. the gcc countries depend mainly on water desalination, which is an expensive process that removes salts and minerals from seawater and brackish water [ ] . there is almost no surface water either in the gcc countries [ , ] . due to the rapid expansion of the population, lifestyle changes have occurred with the urbanization and reclamation of agricultural areas, where valuable groundwater is extracted to satisfy the demand for water [ , ] . fortunately, the desalinated seawater can provide an unlimited supply of drinking water, although it does come with a risk when it is inadequately produced and contaminated or if the water treatment systems fails [ ] . prior to pumping desalinated water into the distribution network, the water is chemically treated. in jeddah, saudi arabia, the drinking water is only distributed to properties once or twice per week. the processed water is then stored in private underground tanks for two days. afterwards, the stored water reaches the distribution facilities, where it is pumped to roof tanks on homes and businesses to be available when needed [ ] . in many areas of jeddah, the domestic wastewater system uses a cesspool, which runs next to the underground water storage tanks. the long-term use of a cesspool system has caused a rapid rise in the underground water table. this has led to contamination of potable water stored in the underground tanks [ , ] . in the western provinces of sa, the use of conventional on-site sewage systems is the exclusive pathway to dispose sewage. under ideal conditions, the waste effluent is assimilated and treated within the topsoil that is directly adjacent to the cesspool, without regulation or implementation, to ensure there is enough separation between the bottom of the cesspool and the water table [ ] . it has been confirmed that the fate and movement of the chemical constituents (nitrates) and bacterial contamination from this septic/cesspool effluent mixes into the shallow groundwater, private shallow and deep wells, and dump stations [ ] [ ] [ ] . it is recognized that the on-site sewage disposal systems have contaminated the drinking water sources and subsequently caused health problems in the gulf region. if chemical and bacterial contamination is present in the drinking water, it is expected to have parasitic contamination as well; however, this parameter is under recognized in the gcc countries. although cryptosporidium has been frequently detected in faecal samples of local inhabitants in the gcc countries (sa [ , , ] , kuwait [ ] , uae [ ] , qatar [ ] , and oman [ ] ), they have little published data regarding the occurrence of cryptosporidium in the gulf water supply. however, six studies in sa, uae, and kuwait have investigated cryptosporidium in selected water resources in the gcc (table ) , with interesting outcomes. it is remarkable that cryptosporidium was present in almost all water resources from the gcc countries, which included desalinated water, underground water, bottled water, swimming pools, irrigation water, and chlorinated water from sewage treatment plants [ , , [ ] [ ] [ ] [ ] . in the sa city of al-taif, cryptosporidium has been identified in % of desalinated water samples [ ] . in makkah, another sa city located next to al-taif, the presence of cryptosporidium infection among its inhabitants has been suspected to originate from contamination from the local desalinated water system. due to the similarity and construction of the two desalination water systems, this has led investigators to suspect the desalination water system as the most plausible source of cryptosporidium infection in makkah [ , ] . the high prevalence of cryptosporidium in kuwait has been linked to the winter desert camping areas, where large numbers of overhead water storage tanks are used to store potable water. water tanker trucks transport this desalinated water to these camping places. it is very interesting that the cryptosporidium subtyping result from the contaminated tank water has been identified as c. parvum subtype iia, and that five members of the same family using this water source at the camp were also infected with the same subtype [ ] . this has provided a direct link to contaminated desalinated water as a potential source of cryptosporidium infection. moreover, the contamination of water with oocysts has probably occurred at the end of the water treatment process during distribution [ ] . it has been reported that about . % of underground waters (wells) are contaminated with cryptosporidium in al-taif [ ] . the protected wells were previously found to be contaminated with faecal matter [ ] . it is not be surprising if unprotected wells are contaminated from a variety of sources, such as wastewater effluent, overland flow from manure piles, as well as domestic or wild animal grazing. fossil groundwater covers about two-thirds of the arabian peninsula, and it is the main source of water in the gcc countries [ ] . ground water pollution in the gcc countries has been caused mainly due to over-pumping from wells. however, there are other factors that have contributed to ground water pollution, such as irrigation returns, seawater intrusions, liquid effluents from septic tanks, and agricultural chemicals. these factors have led to the abandonment of many water wells in the gcc countries [ ] . water well pollution highlights the necessity of higher water-protection legislation and conservation to ensure the protection of water supply for all inhabitants [ ] . bottled water in tabuk, jeddah, and mekkah in sa has been reported to be contaminated with cryptosporidium using modified ziehl neelsen (mzn) as a diagnostic method [ , ] . in these two studies, the authors have not given clear details regarding the water samples used in their investigations and they published ambiguous results concerning the bottled water contamination. in comparison, another study from al-taif, using nested pcr and five brands of bottled water (domestic and imported), has reported all samples to be free from cryptosporidium oocysts [ ] . the microbiological quality of bottled water has been the focus in uae since . although authors have mentioned that the presence of bacteria in bottled water can act as an indicator for the possible presence of cryptosporidium, there has been no established method yet to screen the bottled water for this protozoan parasite in the gcc region [ ] . as mentioned from some of the literature, the quality of bottled water can vary between brands. researchers have speculated that it might not be any safer than tap water, unless it is distilled or pasteurized to ensure complete disinfection. the source of the bottled water is also very important, especially if it is collected from a surface water source (e.g., a stream) and it may be more likely to contain cryptosporidium and other microorganisms than bottled water derived from a ground water source (e.g., a well). therefore, it is important for companies that sell bottled water to also list the water source on the product label [ , ] . in one study, indoor and outdoor swimming pools from five emirati schools were found to be contaminated with an average concentration of cryptosporidium between and oocysts/l. the ages of the swimmers were between and years old, who attended - swimming classes per week [ ] . due to the hot weather in the gcc countries, many swimming pools are available at schools, hotels, parks, and residential areas that are frequently used by many individuals from various age groups. formed faecal incidents (poop) pose a risk for the spread of infectious disease, including parasitic protozoa [ ] . the cdc's healthy swimming program has indicated that escherichia coli, a faecal indicator, has been detected in ( %) of the swimming pools samples, and further explains the necessity of regular monitoring for chlorine-resistant cryptosporidium oocysts [ ] . detection can signify that swimmers have introduced contaminated faecal material into swimming pools either when it washes off a swimmer's body or by release of a formed (or diarrhoeal) faecal incident into the water. the overuse of swimming pools can significantly compromise the effectiveness of proper cleaning and decontamination efforts. the risk of contamination for cryptosporidium in swimming pools is therefore estimated to be very high in spite of use of filtration and chlorination as a cleaning and sanitization method [ ] . the usage of chlorine as a water disinfectant is known to be effective against many microorganisms; however, cryptosporidium oocysts are resistant to the effects of chlorine [ ] and various environmental stresses, such as extreme temperature variations [ ] . the oocysts are small ( µm) and have a low infectious dose ( - oocysts), and reportedly has the ability to maintain viability in water longer than - months or longer with the capability to cause epidemics, even after the consumption of purified drinking water [ , , ] . in the gcc countries, bacterial and fungal indices are routinely tested in different water resources [ , , ] ; however, only scientific institutions care to identify the absence or presence of cryptosporidium oocysts in water samples. the dubai municipality environmental safety inspectors, who send samples to the central laboratories, do not consider the presence of cryptosporidium oocysts in swimming pool water as an indicator of its quality, while instead mainly focusing on monitoring for bacterial indicators [ ] . the national, the leading english news service of the uae, has warned against the failure to keep uae pools clean due to insufficient disinfection and expressed concerns for infectious disease in swimming pools, including parasites that are known to cause severe diarrhoea amongst children. they have reported that when humans become infected with cryptosporidium, they can act as carriers and release its chlorine-tolerant-oocysts into the swimming pools, and suggested that uv irradiation be applied instead of ineffective chlorine for the disinfection of swimming pools [ ] . it remains uncertain, however, whether and in what extent uv treatment has a real impact on cryptosporidium during the water treatment process. only public and private action on such warnings in all gcc countries can help protect the most vulnerable populations (e.g., children and immunocompromised individuals) from becoming infected with cryptosporidium. cryptosporidium oocysts have been detected in . % of the irrigation water used in public parks in uae [ ] . cryptosporidium oocysts have also been found in chlorinated water samples, as well as effluent samples collected from sewage treatment plants [ ] -an indication that the water treatment systems (wastewater disinfection) have failed to eradicate the transmissible stages of cryptosporidium in the water treatment process. in the uae, it is not routine to test for the presence of cryptosporidium oocysts in recreational water and reclaimed wastewater, while bacteriological (total and faecal coliforms) indices are the only biological parameters used to assess their water quality [ , ] . the gcc countries produce a large amount of wastewater with an average of . bm /year [ ] . this wastewater has been reported to contain a wide range of pathogens, including parasites, viruses, and bacteria [ ] [ ] [ ] , and represents a real challenge when designing conventional treatment plants that can meet the health guidelines of the environmental protection agency [ ] . status of average renewable water resources per capita in the gcc countries has already shown a warning sign, and due to the water crisis conditions they often use improperly disinfected wastewater for irrigation [ ] . water contamination with cryptosporidium is an under-recognised and under-investigated problem in the gcc countries, and probably one of the main sources of diarrhoeal diseases in the region. political and social support is required to include cryptosporidium and other protozoan parasites in the testing framework for water quality and reuse of treated water. a lack of water surveillance systems has been noted in the gcc countries. water research that includes analyses of the cryptosporidium genotypes and subtypes will help strengthen the available information about the extent of this pathogenic parasite and its main sources. it would be also effective if the gulf governments consider funding infrastructural projects to efficiently treat water using good installation facilities and proper pre-treatment of chemicals in the process design. in the gcc countries, only a small number of studies have been performed on the presence of cryptosporidium in different animals. however, nine of the published studies have emphasized the concept that animals can be a significant source of cryptosporidium infection in the gulf human population. whether they are used domestically or ridden during sporting events or leisure activities, various animals and birds (sheep, goats, calves, camels, lambs, arabian oryx, falcons, and stone curlews) have tested positive for cryptosporidium infection in the gcc region (table ). on a well-managed omani farm that maintains closed herds of goats, sheep, cows, and buffalo, with regular vaccinations, a severe cryptosporidiosis outbreak has been reported in goats [ ] . massive catarrhal enteritis with markedly enlarged mesenteric lymph nodes have been observed in post-mortem goats due to an invasion of large numbers of cryptosporidium oocysts. another diarrhoeal outbreak in the uae that has occurred was in juvenile stone curlews [ ] . although the owner maintained a good breeding system for the stone curlews, they all became infected with cryptosporidium. numerous endogenous cryptosporidial stages were confirmed in their histopathological sections. despite intense supportive care, both outbreaks have resulted in a high mortality in animals ( kid goats and adult animals died) and birds ( stone curlews died). c. parvum has been determined to be the main species that caused both outbreaks; however, both studies failed to recognize the main source of infection [ , ] . domestic livestock, especially goats and sheep, are widely raised for meat production in the gcc countries [ ] . in sa, . % of sheep and . % of goats have been reported to be infected with cryptosporidium on three farms located in riyadh [ ] . in kuwait, likewise a wide range of domestic animals (goats, sheep, lambs, and newborn calves) have been screened for the presence of cryptosporidium infection [ , , ] , where sheep and goats constitute the majority of its livestock. these animals have the ability to adapt to the arid climatic conditions (hot/dry season and wet/cool season). cryptosporidium has been reported to be prevalent in . % and . % of sheep and goats, respectively. c. parvum has been noted to be the dominant species responsible for the high frequency of caprine and ovine cryptosporidiosis, and infection is usually associated with a large-size herd (overcrowding in a closed housing system), poor hygiene, and poor management practices on the kuwaiti farms [ ] . many animals were imported into kuwait, particularly cattle, to re-establish the animal industry after the end of the iraqi invasion. during the first three weeks of life, calves from eight dairy farms in sulaibyia have suffered from severe diarrhoea, being unresponsive to antibiotics, which ended with a calf mortality of % and morbidity of - %. the authors have reported that cryptosporidium was the main attributor to the diarrhoeal aetiology in the neonate calf deaths [ ] . housing pens with dirt floors, accumulated manure with no regular removal, early separation from dams, and an intensive system (large number of animals raised on limited space of land) have all been cited factors in studies that might help ease the transmission of cryptosporidium oocysts in calves [ , ] . infected calves are known to excrete large numbers of cryptosporidium oocysts that might reach millions [ ] and therefore likely able to rapidly transmit the infection among herds. it deserves mentioning that the sequence analysis of the c. parvum spp. in ruminants isolates (iida g and iiaa g r ) from kuwait [ ] have been previously documented as dominant subtypes in the infected kuwaiti children [ ] , suggesting that domestic animals can be potential zoonotic reservoirs for cryptosporidiosis and a source of cross contamination in the environment. similar to the situation in kuwait above for cattle imports, cattle were flown into qatar to raise supplies of milk in the midst of a country blockade led by saudi arabia. according to the bbc news, the dairy cows (holstein) came from germany-the first of about cattle to be imported was first imported into qatar. air, sea, and land restrictions have created turmoil in qatar, which is dependent on imports to meet the basic needs of its . million inhabitants. several thousand cattle were later imported from other countries. it remains unknown what epidemiological significance such animals will have for the distribution of cryptosporidial oocysts in the country. animals, whether enjoyed during sporting events or for riding for pleasure, such as camels and captive birds (falcons and stone curlews), have become the focus of cryptosporidium research in sa and uae countries. in the sa city of riyadh, cryptosporidium has been ranked first among the microorganisms (escherichia coli, corona, and rota virus) that can cause diarrhoea in % of the symptomatic camel calves from that area [ ] . samples of camel faeces in the same city have been noted to be highly infected with cryptosporidium oocysts ( . %) compared to goats and sheep that were screened using mzn and elisa methods in another study [ ] . camels are the principal domestic animal in sa and are used as a source of meat and milk. they are likewise used for racing sports and transportation [ ] . in kuwait, camels are often utilized for pleasure rides beside families who are camping in the desert. although they are reported to be infected with cryptosporidium since [ ] , they were excluded as a possible source of cryptosporidium infection in kuwaiti residents who had been infected during a camping incident [ ] . in uae, researchers have tested for the presence of antibodies against many infectious diseases, including protozoa, and these have been reported in their racing camels [ ] . camel racing in the gulf region has returned to the height of its cultural revival [ ] due to its adaptation to life in the hot and arid regions [ ] . although gulf camels have been known as carriers for many zoonotic parasites [ ] , since , screening for cryptosporidium and other protozoa has been probably ignored in camels and the people in close contact with them. zoonotic pathogens carried by camels are a current future risk to public health [ ] . the role of camels in the transmission, distribution, and maintenance of cryptosporidium in the gcc countries should be investigated by governmental authorities and researchers alike, especially in light of the increased use as an increasing source of protein and a sporting gain. captive bred birds (e.g., falcons and stone curlews) are a popular hobby for arab falconers. in uae, two falcons have been identified with cryptosporidiosis during a routine health check. their faecal samples and lung tissues tested positive for c. parvum. in that study, the two falcons were totally asymptomatic for any intestinal or respiratory signs [ ] . conversely, it was reported that c. parvum caused severe symptomatic manifestations (catarrhal enteritis) with a high mortality rate in captive stone curlews in dubai [ ] . the uae has no routine testing for the presence of cryptosporidium spp. in birds, owing to the lack of regional specialized laboratories. even though both falcons were bred in the uae, unfortunately the authors of the study were unable to identify the source of the c. parvum infection and failed to check their owner, "the first suspect", for the possibility of having cryptosporidiosis [ ] . a greater risk for cryptosporidium infection has been linked to a low socioeconomic status [ , ] and travel to developing countries, where poor water treatment and lack of food sanitation are prevalent [ ] . gulf researchers often use terms like expatriates, immigrants, or guests for people who come to gcc countries seeking a better financial situation. sustained economic stability and rapid socioeconomic developments have attracted expatriate workers with mass influx into the gcc countries. these multinational guest workers are mainly from developing countries with a low socioeconomic status [ ] . a factor that has long been associated with the transmission of parasitic diseases and is one of the main focuses of research in the gcc countries. during the pre-employment stage (at the country of origin), expatriate workers are screened for the presence of ova and intestinal worms via stool analysis and culture. although the expatriates must be free of contagious and infectious diseases (hiv, hcv, and hbv) to be allowed entrance into the gcc countries, cryptosporidium, a known pathogenic protozoan, is generally not included on the medical examination list of investigations [ ] . various studies in different gcc countries (sa, qatar, uae, kuwait, and oman) have monitored for intestinal parasites among expatriates. it has been reported that the majority of these workers, including food handlers, housemaids, domestic helpers, babysitters, drivers, and private cooks, have tested positive for parasitic infections in the arabian gulf [ , , , [ ] [ ] [ ] [ ] [ ] [ ] . the prevalence of cryptosporidium has been investigated among expatriates (adults and children categories) from oman, qatar, sa, and uae (table ) , who have mainly originated from developing countries (afghanistan, bangladesh, ethiopia, india, indonesia, nepal, pakistan, philippine, sri lanka, turkey, egypt, and jordan). these countries are known to be endemic with many infectious diseases, including parasitic diseases. moreover, many risk factors have been reported to be associated with expatriate workers that predispose themselves to cryptosporidiosis [ , , , ] . in the uae, expatriate workers mainly originate from asian, african, and arabic countries, where the majority of them are from asia. these migrant workers from asia have the highest prevalence rate of cryptosporidium infection among the guest worker population. in their home countries, they live in rural settings under crowded conditions and have poor sanitation, predisposing them to infectious diseases. migrant workers are often required to stay in similar living conditions in their cgg work destinations, where they may have to live in labour accommodations and share the same bedroom (with ≥ persons) and toilet (with > persons) with many people [ , ] . during the umrah season in makkah, sa, there is crowding of a hundred thousand muslims from different nationalities with close contact and congestions between the pilgrims and local inhabitants. the overcrowding and overcapacity of available accommodations has been noted as an important risk factors for cryptosporidium infection during the umrah season [ ] . in qatar, expatriates from western and eastern asia as well as north and sub-saharan africa have been examined for risk factors and the prevalence of cryptosporidiosis. in the gcc countries, many asian individuals (indian and filipinos) who hold jobs, such as housemaids, builders, mechanics, cleaners, masons, and carpenters (blue collars), have tested positive for cryptosporidium infection. at the country of origin, expatriates who have been infected with cryptosporidium had many of the risk factors associated with parasitic infection, including a low education level (elementary school only), low home index, low monthly income, and those who were accustomed to using pit latrines [ ] . children of expatriates from the middle east, asia, africa, and the local qatari population have been examined for intestinal parasites, whereas c. parvum was the most common incidental parasite affecting . % of cases. surprisingly, qatari nationals had the highest number of parasitic infections from any other group tested in spite of fewer reported cases in the local qatari population when compared to the expatriate groups ( versus ) [ ] . in oman, it has been reported that many of expatriate indian food handlers were infected with multiple intestinal parasites, including cryptosporidium. the authors have stressed in their report that it is necessary to screen food handlers for parasitic infection using different diagnostic methods, especially before these individuals are allowed to work in restaurants, hotels, factories, and private homes [ ] . poor personal hygiene among expatriate food handlers has been emphasized in the literature to be a significant contributor to foodborne outbreaks [ ] . in the context of good hygiene and safety in food handling, multiple risk factors linked to expatriates in the gcc region are noted to promote cryptosporidiosis, which is a threat to public health. social marginalization in the form of low socioeconomic status, low living standards, low education, overcrowding, and unhygienic practices (lack of personal hygiene and/or non-practicing of proper hand washing before eating or handling food) are high risk factors for cryptosporidium infection. symptomatic expatriates (mainly food handlers and housemaids) have a greater potential to inadvertently introduce contaminated faecal material into the food industry when working with food and food processing facilitates and equipment (indirect pathway) or by infecting another person in the household or business of their employer (direct pathway). if this happens, cryptosporidium oocysts will circulate in the community (locals and expatriates) until this outbreak cycle can be halted. cryptosporidium oocysts are well known to be environmentally stable, allowing them to be highly infective within vulnerable groups (e.g., children and immunocompromised individuals). accordingly, it is crucial to increase the health awareness among expatriates (particularly food handlers, housemaids, and babysitters) about different transmission routes of cryptosporidium and the important requirement for its prevention and control. it is interesting to note that the prevalence of cryptosporidium and other intestinal parasites in expatriates has been reported to be lower in gulf studies when compared to the population of their home countries [ , , ] . there has not been a single study that compares the prevalence of cryptosporidium infection between expatriates who have recently entered a gcc country and those who spent a long period of time there. the discussion table comes with a significant point about the source of infection. either expatriates come from their home country with the infection, or they have been infected in the country of their employment. further studies on the health status of gulf natives are therefore urgently required to get a true estimate of the source of cryptosporidium prevalence and finally answer the following questions: who is infecting whom? do foreigners import cryptosporidium oocysts and other infections to the gulf, or are the gulf locals actually infecting the foreigners? more research is needed to clarify cryptosporidium transmission cycle in the gcc countries. the high economic position of the ggc countries has established itself among the more food-secure and high-income countries in the world. this situation has created significant pressure on the available natural resources and food production capability in the region. the six gcc states have limited control over their food sources and production capabilities with limited sustainability due environmental challenges [ ] . additionally, the population of the gcc countries has significantly expanded due to the invitation of large numbers of expatriate guest workers who are needed to help industrialize and urbanize these affluent oil producing countries. in the gcc region, many efforts have been made to transform the arid deserts into more habitable areas by using progressive desalinization and desertification processes. moreover, many challenges must still be overcome to tackle this difficult environment (high temperature and scarce water), where its soils are sandy, fragile, and poorly enriched with organic matter [ , ] . agricultural land in the gcc countries accounts for . % of total land area available, whereas only - % is actually arable (cropland regularly ploughed or tilled) [ ] . therefore, the gcc countries are forced to rely on imported food to meet their high demands [ , ] . approximately % of the gcc's food and drinks are imported. annually they import around million tons of foods with expectations to increase in the future to satisfy their expanding economies [ ] . therefore, great emphasis is placed on food safety and security for all imported foods into the gcc countries, including legislation and guidelines to safeguard the quality of the imported food [ , ] . however, their traditional food safety systems have not properly developed to identify potential problems (e.g., infectious disease and parasites) in the food supply before they occur, but rather they are organized to respond to foodborne outbreaks [ ] . contaminated food and drinks with cryptosporidium oocysts and other pathogenic microorganisms are important routes for foodborne outbreaks of cryptosporidiosis far and wide. the catering and food service industries use many high-risk food materials (vegetables, fruits, shellfish, and meat) that are potentially contaminated with cryptosporidium and have been responsible for occasional outbreaks in the past [ ] . the gcc countries, along with other middle east countries, have been classified to have the third-highest estimated burden of foodborne diseases per population, directly behind the african and south-east asian regions. foodborne pathogens in these regions have caused illnesses in million people per year, and million of those affected are children under five years [ ] . gastrointestinal infections that are frequently seen in the gulf region are primarily caused by salmonella spp., followed by shigella spp. and other pathogens like hepatitis a virus and parasites [ , ] . consumption of unpasteurized dairy products and commercial meat products have been implicated in foodborne diseases in kuwait, oman, and sa [ , ] . in jeddah, sa, there has been a rapid increase in the number of fast food businesses owned by immigrants from developing countries who have not had adequate training in food hygiene. fast food dishes have a great potential for food contamination due to undercooked meat that does not reach the criterial temperatures to kill microorganisms [ , ] . there are scattered reports about the role of bacteria and viruses as causative agents of foodborne diseases throughout the gcc region. often, parasites, including cryptosporidium, are the causative agents in foodborne diarrhoea; however, the actual available reports on diarrhoeal cases in the arabian gulf are scarce or non-existent. only one study in qassim, sa, has investigated the different types of leafy vegetables (green onion, red radish, garden rocket, lettuce, and parsley) for the presence of parasites. the authors reported that all vegetables tested in the study had been contaminated with a variety of parasites, such as giardia, balantidium coli, entamoeba, cryptosporidium, trichuris, enterobius, and taenia [ ] . other foodborne outbreaks have been documented in sa [ ] . however, microbiological surveillance has been performed in the reported foodborne outbreaks, while only salmonella spp. and staphylococcus aureus were the identified pathogens from outbreaks. moreover, the authors declared that many foodborne outbreaks occur every year in the kingdom of sa [ ] ; however, cryptosporidium and other foodborne parasites have been nevertheless excluded from such investigations. the gcc ministerial committee for food safety has established joint legislation and regulations on food safety based upon the certainty that imported foods may represent human health and environmental safety challenges. the food safety guidelines represent health certificates forums, technical regulations, and standards that list food categories and their certification requirements. the technical regulations emphasize the microbiological criteria and the general safety standards for contaminants and toxins [ ] . regrettably, the guidelines do not specify any regulations or laws concerning food safety from parasitic contamination, which have caused foodborne outbreaks such as cryptosporidiosis. it is important to note that imported food could be contaminated with cryptosporidium oocysts (a) from the country of origin due to contamination from animal or human faeces in the water or soil sources used to produce the food, or infected individuals that grow and store the food; (b) from infected individuals transporting the food on the way to the designated country; or (c) from within the destination country via infected food handlers or businesses that store the imported food in improper conditions or washing and preparing food with contaminated water. gcc countries must apply well-developed strategies for prevention and control of foodborne cryptosporidiosis. the food security strategies must include surveillance systems in the health care system and food industry that monitor for the presence of cryptosporidium oocysts. in addition, they must establish an epidemiological information system with local governmental authorities that also partners with applied researchers towards the advancement of technologies that can effectively detect and disinfect oocysts in food and water supply. there are needs to be a modification of current regulatory standards that specifically includes parasitic contamination in imported food and educational programs made available to food handlers in order to further reduce the risk and the incidence of foodborne illnesses, such as cryptosporidium infection. the miniscule size of cryptosporidium oocysts has the capability to disseminate across the air, where they could be inhaled and cause infection in humans and animals [ ] . inhalation of oocysts from contaminated air can infect the respiratory tract and manifest respiratory symptoms [ ] [ ] [ ] . cryptosporidium oocysts have been observed in % of the investigated air samples in mexico [ ] . direct contamination with faecal material because of the lack of sanitary infrastructure results in a greater dispersion of soil via airborne dust during dry season, particularly in those places where people are exposed to large amounts of outdoor dust [ ] . the gcc countries are characterized by arid climatic conditions (long, dry, hot summers and short, relatively warm winters) [ , , ] . weather conditions, such as heat, wind, and a lack of rainfall, have significantly contributed to dust and the formation of the gcc countries' regional climate [ ] . therefore, the gulf population has a higher exposure to large amounts of outdoor dust, which puts them at risk for cryptosporidium infection from contaminated air particles; more so if they have close contact with infected livestock. it has been reported in the epidemiology of cryptosporidiosis that respiratory aerosol droplets from infected individuals can be one of the crucial factors in the transmission, rapid spread, and continuous circulation of cryptosporidium oocysts. evidence has suggested that oocysts can be transmitted via respiratory secretions as well as through the more common faecal-oral route [ ] . it has been documented that wind can increase the spread of viruses in the saliva and respiratory droplets when someone coughs or sneezes. studies have demonstrated that airborne particles from sneezes can travel up to m in . s with an accelerated dispersion rate [ ] . the same scenario also could occur with respiratory droplets from individuals infected with cryptosporidium oocysts. it has been shown that cryptosporidium oocysts are able to infect epithelial organoids derived from human lungs and are successfully able to complete their lifecycle [ ] . the risk of illness for cryptosporidium oocyst air inhalation has been found to be very high and has shown to reach above the safety guidelines of its presence in water ( × − ) [ ] . with or without symptoms, cryptosporidium oocysts are involved in the respiratory tracts of avian and some mammals, which includes a small number of human cases [ ] . all of the published research studies from the gcc countries have not included or excluded questions regarding respiratory symptoms in the diagnosis. however, respiratory cryptosporidium infections have been reported to occur in immunocompetent children with enteric cryptosporidiosis, individuals with an unexplained cough, and in immunocompetent adults with tuberculosis from uganda [ , ] . it is worthy to stress that % of children with intestinal cryptosporidiosis and cough had cryptosporidium dna in their respiratory secretions [ ] , which validates the potential for cryptosporidium to be transmitted by cough, sneeze, and expectoration from those who have cryptosporidial infections and diarrhoea. in the uae, two asymptomatic captive falcons were identified to have cryptosporidiosis and tested positive for c. parvum in their lung tissues by molecular analysis. in addition, the main endoscopic findings from the cases indicated an infectious process in the ostia, caudal lung field, and caudal thoracic air sacs with an accumulation of inflammatory cells. acid-fast positive cryptosporidial oocysts was identified as the cause of the infections in the report [ ] . although, the cryptosporidium infection in the falcon's lungs could have come from the spread of infection from its intestines, the airborne transmission should also be taken into consideration as the initial source of infection, which further illustrates the potential for airborne cryptosporidium transmission in humans. there are a limited number of respiratory cryptosporidiosis cases reported in the gulf countries; however, the extent of this type of lung infection has yet to be established in the region. more research is needed to verify the actual risk from cryptosporidial respiratory tract infections in the gulf human and animal populations. already researchers have shown that breathing has the potential to release aerosols from infective individuals into a room [ ] . recently, investigators have reported the use of computational multiphase fluid dynamics and heat transfer to demonstrate the transport, dispersion, and evaporation of saliva and respiratory particles that can arise from the human cough. they have calculated the effect of wind speed on social distancing safety measures during the covid- pandemic. interesting to note that when they considered all the environmental conditions, they concluded that a safety measure of m between people is insufficient to completely prevent the inhalation of respiratory particles and droplets [ ] . it is advisable that when managing patients infected with enteric cryptosporidiosis, particularly in those who have unexplained respiratory symptoms, they should be isolated or given face masks as a precautionary measure to avoid the spread of cryptosporidium oocysts from their respiratory droplets that can be released when coughing or sneezing. therefore, patients should be advised to always protect their mouths and noses with handkerchiefs when they cough or sneeze. routine diagnostic and surveillance systems are an important part of public health and the treatment of infectious diseases. they have the power to prevent outbreaks and save lives. cryptosporidium and other parasites have not yet been included in the routine diagnostic and surveillance systems of the gulf regions. however, the apparent disease burden of parasitic infections and other infectious disease has been cited in the literature from these gcc countries. the limited number of reports that was found in this review indicate that cryptosporidium has almost infected every element of the gulf region; in addition, the burden of this parasite in humans, animals, and food and water supplies is starting to show up more in the published literature. cryptosporidium has definitely had a negative impact on the economic prosperity and public health in this region, while much of this burden has been underrecognized, underestimated, and underreported in reports. many of the risk factors for contracting cryptosporidium are an everyday reality for the inhabitants of the gcc countries. the most vulnerable groups (e.g., children under years and immunocompromised individuals) are the most susceptible to the adverse effects of cryptosporidiosis and should be protected from this preventable infectious disease. molecular analysis of cryptosporidium from isolates in the gulf population have revealed the presence of zoonotic and anthroponotic transmission according to the published reports. desalinated water and other drinking water sources in the gcc countries have been found to be contaminated with cryptosporidium oocysts. defective waste management systems and water treatment plants have been found to be a source of septic pollutants in the drinking water supplies. camels and other animals often accompany owners to sporting events and leisure activities in the gcc countries, which has been noted to be a significant source of zoonotic cryptosporidiosis in the region. cryptosporidium outbreaks have been recorded in animals by incidental or accidental findings. authors have commented that many of these cryptosporidiosis outbreaks in animals from gulf region continue be undetected or underreported in the literature. expatriates workers have been found to be a source of "imported" cryptosporidium infection via food handling and poor hygiene; however, more detailed investigations are needed to compare this group of the population with the native inhabitants of the area. large quantities of food are imported to feed the expanding work force in the gulf region. food is usually imported from low socioeconomic countries that are associated with a higher risk of contracting cryptosporidiosis due to their social and economic situation. food safety and security legislation has been enacted in the gcc countries to prevent foodborne outbreaks in the region. however, their regulatory standards for imported food still lack many of the parasites known to cause outbreaks, such as cryptosporidium, in their screening protocols. this needs to urgently change so that the prosperity of the local economy and the most vulnerable populations are protected from the burden of foodborne outbreaks in the gulf region. imports of animals, such as cattle, may impact the known epidemiological importance of the release and transmission of cryptosporidium oocysts. a new animal reservoir with its related implications is generated in the gcc countries due to political tensions in the region. further research is required to quantify the influence of transmission parameters such as the infective airborne respiratory droplets of cryptosporidium on disease burden, along with those of other pathogenic microorganisms. more research is needed for the development of highly effective disinfection methods to treat cryptosporidium contamination in swimming pools and the water supplies, e.g., bottled water and ground water. the gcc countries should include cryptosporidium and other parasitic pathogens in their public health protocols for the routine screening of infectious diseases in human and animal faecal samples who have contact with the food and water supply in order to avoid outbreaks. the airborne transmission of cryptosporidium oocysts is highlighted due to the particularly windy and dry environmental conditions associated with this region. the wind has the power to circulate minuscule particles of dried infective faecal matter in the surrounding areas that can poses a threat to human and animal health. more published research is needed on the epidemiology of cryptosporidium in order to determine the true prevalence of this parasitic pathogen in the gcc countries. funding: this review received no external funding. a one health approach to tackle cryptosporidiosis evolution of monitoring for giardia and cryptosporidium in water genetic polymorphism in cryptosporidium species: an update cryptosporidium infection risk: results of new dose-response modeling cryptosporidium proventriculi sp. n. (apicomplexa: cryptosporidiidae) in psittaciformes birds cryptosporidium cuniculus-new records in human and kangaroo in australia. parasites vectors subtyping cryptosporidium ubiquitum, a zoonotic pathogen emerging in humans prevalence and genotypic identification of cryptosporidium spp. and enterocytozoon bieneusi in captive asiatic black bears (ursus thibetanus) in heilongjiang and fujian provinces of china the first evidence of cryptosporidium meleagridis infection in a colon adenocarcinoma from an immunocompetent patient genetic diversity and population structure of cryptosporidium morbidity, mortality, and long-term consequences associated with diarrhoea from cryptosporidium infection in children younger than years: a meta-analyses study diarrheal diseases waterborne transmission of protozoan parasites: a worldwide review of outbreaks and lessons learnt waterborne transmission of protozoan parasites: review of worldwide outbreaks-an update waterborne transmission of protozoan parasites: review of worldwide outbreaks-an update - water-borne protozoa parasites: the latin american perspective foodborne cryptosporidiosis an overview of methods/techniques for the detection of cryptosporidium in food samples the impact of water crises and climate changes on the transmission of protozoan parasites in africa cryptosporidium and cryptosporidiosis: the african perspective findings from the global burden of disease study cryptosporidium and cryptosporidiosis: the asian perspective global burden of diarrheal diseases among children in developing countries: incidence, etiology, and insights from new molecular diagnostic techniques the burden and etiology of diarrheal illness in developing countries burden and aetiology of diarrhoeal disease in infants and young children in developing countries (the global enteric multicenter study, gems): a prospective, case-control study the burden of cryptosporidium diarrheal disease among children < months of age in moderate/high mortality regions of sub-saharan africa and south asia, utilizing data from the global enteric multicenter study (gems) accounting for long-term manifestations of cryptosporidium spp infection in burden of disease and cost-of-illness estimations, the netherlands outbreaks linked to swimming have doubled since risk factors for cryptosporidium infection in low and middle income countries: a systematic review and meta-analysis global distribution, public health and clinical impact of the protozoan pathogen cryptosporidium enteric protozoa in the developed world: a public health perspective water security in the gcc countries: challenges and opportunities demographic and health indicators in gulf cooperation council nations with an emphasis on qatar climate change threats, opportunities, and the gcc countries food security in the gulf cooperation council countries: challenges and prospects water availability and quality in the gulf cooperation council countries: implications for public health food security in the gulf cooperation council effects of weather and river flow on cryptosporidiosis cryptosporidiosis in kuwaiti children: seasonality and endemicity identification of giardia lamblia and the human infectious-species of cryptosporidium in drinking water resources in western saudi arabia by nested-pcr assays review article: gastrointestinal infections in deployed forces in the middle east theater: an historical year perspective military importance of diarrhea: lessons from the middle east international association for medical assistance to travellers childhood diarrhoea in the eastern mediterranean region with special emphasis on non-typhoidal salmonella at the human-food interface cryptosporidium spp., prevalence, molecular characterisation and socio-demographic risk factors among immigrants in qatar molecular analysis of the enteric protozoa associated with acute diarrhea in hospitalized children prevalence of, and factors associated with intestinal parasites in multinational expatriate workers in al ain city, united arab emirates: an occupational cross-sectional study prevalence of cryptosporidium spp. among asymptomatic healthy expatriate workers in sharjah, united arab emirates cryptosporidiosis in kuwaiti children: association of clinical characteristics with cryptosporidium species and subtypes unique endemicity of cryptosporidiosis in children in kuwait intestinal parasitic diseases in riyadh, saudi arabia: prevalence, sociodemographic and environmental associates gulf cooperation council countries and the global land grab. arab world geogr patterns of infection with intestinal parasites in qatar among food handlers and housemaids from different geographical regions of origin detection of cyclospora cayetanensis, cryptosporidium spp., and toxoplasma gondii on imported leafy green vegetables in canadian survey detection of cryptosporidium oocysts and giardia cysts in vegetables from street markets from the qinghai tibetan plateau area in china a review of the global burden, novel diagnostics, therapeutics, and vaccine targets for cryptosporidium intestinal parasitic infection among new refugees to minnesota infectious disease surveillance and control enteroparasitic occurrence in stools from residents in southwestern region of saudi arabia before and during umrah season evaluation of the xtag gastrointestinal pathogen panel assay for the detection of enteric pathogens in kuwait cryptosporidium gastroenteritis in immunocompetent children from kuwait usefulness of kato-katz and trichrome staining as diagnostic methods for parasitic infections in clinical laboratories cryptosporidiosis in children from the sultanate of oman prevalence of cryptosporidiosis in dammam and alkhobar, saudi arabia prevalence of cryptosporidium-associated diarrhea in a high altitude-community of saudi arabia detected by conventional and molecular methods cryptosporidiosis in two regions of saudi arabia high frequency of enteric protozoan, viral, and bacterial potential pathogens in community-acquired acute diarrheal episodes: evidence based on results of luminex gastrointestinal pathogen panel assay comparison of kinyoun's acid-fast and immunofluorescent methods detected an unprecedented occurrence of cryptosporidium in the eastern region of saudi arabia prevalence of cryptosporidium species isolated from diarrheic children in makkah, saudi arabia detection of cryptosporidium amongst diarrhoeic and asymptomatic children in jeddah, saudi arabia intestinal parasites infection among immunocompromised patients in riyadh, saudi arabia. pak cryptosporidiosis in young children suffering from diarrhoea in riyadh, saudi arabia prevalence of intestinal parasitic and bacterial pathogens in diarrhoeal and non-diarrhoeal school children's at hail cryptosporidiosis among immunocompromised patients in saudi arabia prevalence of intestinal parasitic infections among patients of king fahd medical city in riyadh region, saudi arabia: a -year retrospective study prevalence and genotyping of cryptosporidium in stool samples collected from children in taif city (saudi arabia) prevalence and genotyping of cryptosporidium in stool samples collected from children in taif city (saudi arabia) multilocus genetic analysis of cryptosporidium isolates from saudi arabia prevalence of intestinal parasite infections among patients in local public hospitals of hail, northwestern saudi arabia. asian pac eradication of cryptosporidium in four children with acute lymphoblastic leukemia infectious and parasitic disease mortality in kuwait and the role of health education world bank national accounts data, and o.n.a. data files. gni per capita, atlas method (current us$). . data intestinal parasites in the state of bahrain economy of bahrain united nation development program cryptosporidiosis in the arabian gulf: report of two cases from kuwait environmental risk factors for diarrhoea among male schoolchildren in jeddah city, saudi arabia burden of acute gastroenteritis among children younger than years of age-a survey among parents in the united arab emirates considerations for introduction of a rotavirus vaccine in oman: rotavirus disease and economic burden comparison of current methods used to detect cryptosporidium oocysts in stools genetic characterization and transmission cycles of cryptosporidium species isolated from humans in new zealand cryptosporidiosis: a zoonotic disease concern cryptosporidium parvum iid family: clonal population and dispersal from western asia to other geographical regions genotypes and subtypes of cryptosporidium spp. in diarrheic lambs and goat kids in northern greece epidemiological observations on cryptosporidiosis and molecular characterization of cryptosporidium spp. in sheep and goats in kuwait advances and perspectives on the epidemiology of bovine cryptosporidium in china in the past years prevalence and characterization of cryptosporidium spp. in dairy cattle in nile river delta provinces longitudinal prevalence, oocyst shedding and molecular characterisation of cryptosporidium species in sheep across four states in australia molecular epidemiology of cryptosporidiosis in china comparison of elisa and microscopy for detection of cryptosporidium oocysts in animals common occurrence of cryptosporidium hominis in asymptomatic and symptomatic calves in france molecular epidemiology of cryptosporidiosis: an update genotype analysis of cryptosporidium meleagridis isolates from humans in japan wastewater reuse in the countries of the gulf cooperation council (gcc): the lost opportunity environmental impacts of seawater desalination: arabian gulf case study importance weighting of impacts in environmental impact studies alternative solutions and mitigation measures of a sewerage system identification of the potential sources of nitrate in groundwater from shallow aquifer in wadi qudaid, western part of saudi arabia effects of cesspool systems on groundwater quality of shallow bedrock aquifers in the recharge area of wadi fatimah, western arabian shield, saudi arabia the hygienic-related microbiological quality of drinking water sources al-baha province, kingdom of saudi arabia assessment of drinking water quality prevalence of cryptosporidium and giardia lamblia in water samples from jeddah and makkah cities-neliti a preliminary assessment of the occurrence of cryptosporidium and giardia in the school swimming pool water in dubai, united arab emirates ia _proceedings_open_online_surgical_ education_the_experience_in_hand_surgery_march_ _p - .pdf? =&response-content-disposition=inline% b+filename% dopen_online_surgical_education_the_exper.pdf&expires= &signature=d quu i wixg iohgn-lzgjjrane~{}~{}ayjwxqgfcx khafllyw jty g-hnnwrznnci-ca sg tsk~{}uuvzvlwsedqehbyz f yxcb tiusbll z b qhyhb{ }klrx ywfbf lf iagonat ar zedmib~{} ckpdyjfljrkdw hgzwxkl k ffsd -sx xmzz pywixurucq gu pc g wlge iz suaboeaqktm fttumrhmqnywcdjcsl gsqqfr- eewlyblwsklj~{}pmhaouta erc ulrqxcpvcjexaj bfp qztci jjyhyk dwsnf dwgktt ijvxivdcng_ _&key-pair-id=apkajlohf ggslrbv za cryptosporidium and giardia infection and drinking water sources among children in lege dini water resources in the gcc countries: an overview water issues in the gulf: time for action occurrence of giardia and cryptosporidium in water supplies of russia and bulgaria microbiological quality of bottled drinking water in the uae and the effect of storage at different temperatures new jersey department of health and senior services facts: cryptosporidium in drinking water incident response recommendations for aquatic staff microbes in pool filter backwash as evidence of the need for improved swimmer hygiene-metro-atlanta effects of ozone, chlorine dioxide, chlorine, and monochloramine on cryptosporidium parvum oocyst viability protozoan parasites in drinking water: a system approach for improved water, sanitation and hygiene in developing countries the truth about in vitro culture of cryptosporidium species environmental prevalence of pathogens in different drinking water resources in makkah city (kingdom of saudi arabia) microbial water quality and sedimentary faecal sterols as markers of sewage contamination in kuwait failure to keep uae pools clean may endanger children, experts warn-the national bacteriological quality of reclaimed wastewater used for irrigation of public parks in the united arab emirates hydrogeology of an arid region: the arabian gulf and adjoining areas-google books water resources in arid areas: the way forward membrane bioreactor-based wastewater treatment plant in saudi arabia: reduction of viral diversity, load, and infectious capacity balanced urban development: options and strategies for liveable cities; water science and technology library preliminary study on cryptosporidiosis in livestock from kuwait infectious causes of neonatal diarrhea in cattle in kuwait with special reference to cryptosporidiosis atypical outbreak of caprine cryptosporidiosis in the sultanate of oman camel calf diarrhoea in riyadh region, saudi arabia parasites of the arabian oryx (oryx leucoryx, pallas, ) and their prevalence in the kingdom of saudi arabia first detection of cryptosporidium parvum in falcons (falconiformes): diagnosis, molecular sequencing, therapeutic trial and epidemiological assessment of a possible emerging disease in captive falcons an outbreak of cryptosporidiosis in a collection of stone curlews (burhinus oedicnemus) in dubai sustainable agriculture in the arabian/persian gulf region utilizing marginal water resources: making the best of a bad situation role of cryptosporidium parvum as a pathogen in neonatal diarrhoea complex in suckling and dairy calves in france prevalence rate of intestinal parasites in camels in riyadh, saudi arabia chronic cryptosporidiosis in a bactrian camel (camelus bactrianus) survey of antibodies against various infectious disease agents in racing camels in abu dhabi camel racing in the gulf notes on the evolution of a traditional cultural sport zoonotic parasites of dromedary camels: so important, so ignored. parasites vectors a review of parasites of camels (camelus dromedarius) in saudi arabia a review of zoonotic pathogens of dromedary camels cdc. sources of infection & risk factors/prasites-cryptosporidium. cdc rules & regulations for medical examination of expatriates coming to gcc states for residence prevalence of intestinal parasites and bacteria among food handlers in a tertiary care hospital comparative study of intestinal parasitic infestation among food handlers in abu dhabi (u.a.e.) - cysticercosis/t. solium taeniasis, a potential public health concern in non-endemic country, kuwait: a new diagnostic method to screen t. solium taeniasis carriers among the expatriate population intestinal parasitic infections among expatriate workers in al-madina al-munawarah, kingdom of saudi arabia the prevalence of intestinal parasitic infections among foreign workers in madinah, kingdom of saudi arabia a spectrum of pathogenic and non-pathogenic intestinal parasites in pre-employment medical check-up for workers and their families surveillance for foodborne-disease outbreaks-united states intestinal parasitic infections among expatriate workers in various occupations in sharjah food security in the gulf cooperation council (gcc) economies. gcc network for drylands research and development (ndrd) developments in soil classification, land use planning and policy implications: innovative thinking of soil inventory for land use planning and management of land resources special focus: middle east and north effective seafood safety and quality management systems:an analysis of the situation in the sultanate of oman assessment of the food control systems in the sultanate of oman prevention and control of foodborne diseases in middle-east north african countries: review of national control systems foodborne diseases burden epidemiology reference group food hygiene in past ten years in saudi arabia incidence and control of brucellosis in the near east region food poisoning in saudi arabia. potential for prevention? the prevalence of leafy vegetable-borne parasites in al-qassim region, saudi arabia surveillance for foodborne illness outbreaks in qassim the cooperation council for the arab states of the gulf. gcc guide for control on imported foods occurrence and quantitative microbial risk assessment of cryptosporidium and giardia in soil and air samples respiratory cryptosporidiosis in hiv-seronegative children in uganda: potential for respiratory transmission expectoration of cryptosporidium parasites in sputum of human immunodeficiency virus-positive and -negative adults the evolution of respiratory cryptosporidiosis: evidence for transmission by inhalation regional climatic features of the arabian peninsula on coughing and airborne droplet transmission to humans modelling cryptosporidium infection in human small intestinal and lung organoids infectious virus in exhaled breath of symptomatic seasonal influenza cases from a college community this article is an open access article distributed under the terms and conditions of the creative commons attribution (cc by) license we would like to acknowledge chad schou, university of nicosia medical school, , cy- , nicosia, cyprus, for the time and effort devoted to improving the linguistic quality of this review. we write to express our appreciation for his detailed and useful comments, which have much improved the english language level of this review. key: cord- -jc k fki authors: gardner, emma g.; kelton, david; poljak, zvonimir; van kerkhove, maria; von dobschuetz, sophie; greer, amy l. title: a case-crossover analysis of the impact of weather on primary cases of middle east respiratory syndrome date: - - journal: bmc infect dis doi: . /s - - - sha: doc_id: cord_uid: jc k fki background: middle east respiratory syndrome coronavirus (mers-cov) is endemic in dromedary camels in the arabian peninsula, and zoonotic transmission to people is a sporadic event. in the absence of epidemiological data on the reservoir species, patterns of zoonotic transmission have largely been approximated from primary human cases. this study aimed to identify meteorological factors that may increase the risk of primary mers infections in humans. methods: a case-crossover design was used to identify associations between primary mers cases and preceding weather conditions within the -week incubation period in saudi arabia using univariable conditional logistic regression. cases with symptom onset between january – december were obtained from a publicly available line list of human mers cases maintained by the world health organization. the complete case dataset (n = ) was reduced to approximate the cases most likely to represent spillover transmission from camels (n = ). data from meteorological stations closest to the largest city in each province were used to calculate the daily mean, minimum, and maximum temperature ((ο)c), relative humidity (%), wind speed (m/s), and visibility (m). weather variables were categorized according to strata; temperature and humidity into tertiles, and visibility and wind speed into halves. results: lowest temperature (odds ratio = . ; % confidence interval = . – . ) and humidity (or = . ; % ci = . – . ) were associated with increased cases – days later. high visibility was associated with an increased number of cases days later (or = . ; % ci = . – . ), while wind speed also showed statistically significant associations with cases – days later. conclusions: results suggest that primary mers human cases in saudi arabia are more likely to occur when conditions are relatively cold and dry. this is similar to seasonal patterns that have been described for other respiratory diseases in temperate climates. it was hypothesized that low visibility would be positively associated with primary cases of mers, however the opposite relationship was seen. this may reflect behavioural changes in different weather conditions. this analysis provides key initial evidence of an environmental component contributing to the development of primary mers-cov infections. middle east respiratory syndrome coronavirus (mers--cov) is an emerging zoonotic agent that was first isolated in from a patient hospitalized in saudi arabia [ ] , and has since infected over people with a % case fatality ratio [ ] . after an incubation period of - days [ ] , the virus causes a disease (middle east respiratory syndrome, or mers) characterized by fever, cough, and shortness of breath, which commonly leads to pneumonia and respiratory failure [ ] . the virus circulates silently in dromedary camels, the only known reservoir species and zoonotic source of spillover to humans [ ] . however, not all primary human cases have documented exposure to dromedaries or their products, such as milk and meat. although human-to-human community-acquired infections have not been documented, there is evidence that asymptomatic infections of mers-cov exist and could be a source of community transmission [ ] . zoonotic spillover from dromedary camels to humans has been documented in the arabian peninsula [ ] . subsequent secondary cases can occur after unprotected contact with family members and within healthcare facilities once the primary case seeks medical assistance [ ] . while the sizes of mers-cov outbreaks have decreased thanks to improved infection control in healthcare settings in affected countries, cases continue to be reported regularly, especially in saudi arabia, where surveillance is strong [ ] . in order to further reduce cases and prevent human outbreaks, a better understanding of zoonotic transmission of mers-cov is needed. a deeper understanding of the epidemiology of primary human cases can inform evidence-based interventions at the level of the community at the animal-human interface. zoonotic modes of mers-cov transmission have not yet been definitively determined. mers-cov in dromedary camels causes a mild upper respiratory infection with no documented viremia [ ] , and therefore droplet or aerosol transmission by close camel contact is most likely. however, transmission through contaminated milk, meat, and urine is possible, although the contribution of camel products cannot currently be estimated due to a lack of scientific evidence. the effects of weather and environmental conditions on respiratory diseases with similar modes of transmission (direct contact or droplet), such as influenza and respiratory syncytial virus, have been documented. temperature and humidity are associated with transmissibility of influenza virus [ ] , and the seasonality of both influenza and respiratory syncytial virus is linked to these two factors [ ] . air quality is also associated with respiratory infections. air pollution has been linked to pneumonia and acute lower respiratory infections [ , ] , while dust storms are associated with infectious respiratory disease by acting both as a carrier of pathogens and increasing airway susceptibility to infection [ ] . the risk of acquiring primary mers may be influenced by changes in weather conditions in two ways. first, weather conditions may affect the viability and persistence of the virus in the environment and therefore its transmissibility [ , ] . secondly, weather influences behaviour, and it is plausible that the likelihood of people contacting camels depends on environmental conditions. seasonal or meteorological patterns of primary mers-cov infections have yet to be explored. this study examined whether meteorological conditions were associated with the development of known primary mers-cov infections using a case-crossover study design. case-crossover studies are designed so that exposures during a period of interest before a case are compared to exposures during control periods before or after the case. in this regard, case-crossover studies answer the question "why now?" as opposed to "why these subjects?" [ ] . the design is well suited for rare diseases with short incubation periods such as mers-cov. the effect period, that is, the period of time after the proposed "trigger", typically has a degree of uncertainty [ ] , leading to exposure windows with intervals of biological relevance to the outcome of interest. for infectious diseases, this would equate to the incubation period [ ] . furthermore, with appropriate selection of referent windows, the case-crossover design controls for confounding effects of temporal fluctuations such as climatic and livestock-associated seasons (e.g. the dromedary breeding cycle) [ ] . by comparing weather conditions immediately before mers cases to weather conditions at other times, this study aimed to identify environmental factors that are associated with primary human mers in saudi arabia. the world health organization (who) maintains a list of all human laboratory confirmed cases of mers-cov. publicly available case data from january -december were obtained. case data prior to were excluded due to a lack of standardized data collection prior to [ ] . a mers case was defined throughout the study period as "a person with laboratory confirmation of mers-cov infection irrespective of clinical signs and symptoms" [ ] . of the confirmed cases with onset dates between january -december , cases were removed where exposure to camels and camel products were known not to have occurred. geographically, cases were restricted to those reported from saudi arabia, where the province of exposure was provided (n = ). cases that were likely primary cases were retained by excluding healthcare workers and cases with documented contact with known mers cases (n = ). cases were further removed where symptom onset date was after hospitalization date (n = ). of the remaining cases (n = ), ( . %) had missing symptom onset dates. to retain these ten cases, the median time between symptom onset date and lab confirmation date was calculated ( days) and subtracted from the lab confirmation date to obtain an estimate of the symptom onset date. visual inspection of the timeline of retained cases identified a spike from riyadh province around august , which corresponds to a documented mers-cov outbreak in the city of riyadh from july-september . data from a published report of the outbreak contained weekly counts of primary and secondary cases [ ] . these weekly counts were compared with the case list for this analysis and thirty-two secondary cases associated with the riyadh outbreak were removed. the final number of retained cases fitting the primary case definition was ( fig. ). for the purposes of the descriptive results, age groups were chosen for ease of reading while still providing a visualization of the distribution, and according to age categories provided by the statistical yearbook of the general authority for statistics of the kingdom of saudi arabia, which was used for standardization. meteorological stations closest to the largest city in each province were identified by a numeric identifier and location using google earth [ ] (fig. ) . meteorological data were obtained from the noaa global hourly index [ ] . the daily mean, minimum, and maximum temperature, wind speed, and visibility were calculated. relative humidity was calculated using temperature and dew point data [ ] . a case-crossover design was used to explore the associations between primary mers cases and preceding meteorological conditions [ , ] . each case's exposure status on individual days before disease onset (the exposure window) was compared to the exposure status on different days during a control period. under the assumption that weather effects on virus transmission were immediate, the exposure window, that is, the time lag between weather events and disease onset, was set to be equal to the mers incubation period of - days [ ] . univariable conditional logistic regression was used to assess statistical associations between cases and weather variables on each day within the case and control exposure windows. associations with p < . were considered statistically significant. a time-stratified design was used, with a -day strata length with random bi-directional controls matched by day of the week. using a -day time window provides at least three control days for each case exposure day while minimizing bias introduced from seasonal changes [ ] . temperature and humidity variables were categorized into tertiles calculated within each time stratum. wind speed and horizontal ground visibility were categorized into two groups within each stratum with the median as cutoff. therefore, there is no single threshold for each weather variable, but rather "low", "medium" and "high" are determined according to the measurements in each stratum. statistical analyses were conducted using stata . (stata corporation, college station, tx). four hundred and forty-six cases of mers-cov in saudi arabia with symptom onset dates between january -december were included in the analysis. table presents the case counts as well as crude and age-and sex-standardized rates by province, sex, and age group. all provinces in saudi arabia reported cases during this -year period. riyadh province had the highest count of reported cases with cases ( %), although qasseem had the highest cumulative incidence ( . cases per , people), followed by riyadh ( . cases per , people). the median age of cases was years (range, - ), and % of cases were male. age and sex proportions are similar to figures reported for primary cases in previously published literature [ ] . figure presents the case count by month from to for the entire country. cases were reported in every month of the year, although no clear seasonality is apparent. temperature and humidity conditions were associated with case occurrence - days later. the odds of a mers case days after low minimum temperatures was . ( % confidence interval [ci], . - . ) higher than after control days, while low mean daily temperature was similarly associated with cases at (or, . ; % ci, . - . ) and day lags (or, . ; % ci, . - . ) (fig. ) . conversely, high minimum, maximum, and mean temperatures were protective at similar lag days. for example, the odds ratios of mers cases for the high mean daily temperature was . ( % ci, . - . ) with a -day lag, and . ( % ci, . - . ) with a -day lag. humidity followed a similar pattern to temperature. when maximum daily humidity was low days earlier, the odds ratio for a mers cases was . ( % ci, . - . ). high humidity was associated with fewer cases across all three daily measurements (fig. ) . for example, the odds ratios of cases for high maximum daily humidity was . ( % ci, . - . ) and . ( % ci, . - . ) at -and -day lags, respectively. high visibility was positively associated with occurrence of a mers case days later, whereas low visibility demonstrated protective effects for risk of mers (fig. ) . the odds of a mers case days after both minimum and mean daily visibility were high was . and . times higher than after control days ( % ci, . - . and . - . ). conversely, when minimum and mean wind speed results were conflicting, with low minimum daily wind speed and high maximum wind speed both positively associated with cases at similar time lags (fig. ) . the odds of a mers case was . times higher days after low minimum wind speed ( % ci, . - . ), while the odds ratio of cases for when minimum wind speed was relatively high was . ( % ci, . - . ). conversely, the odds of a case when maximum wind speed was relatively high was . ( % ci, . - . ) (not shown in figure) . mers is a global public health threat that causes severe respiratory disease with a high case fatality ratio, identified by who as a priority pathogen for research and development in public health emergency contexts [ ] . it is primarily characterized by healthcare-associated outbreaks triggered by index cases who acquire infection from dromedary camels and possibly from unidentified asymptomatic human carriers. improving our understanding of the epidemiology and risks of primary cases of mers is vital for designing effective interventions that aim to reduce these index cases and prevent subsequent outbreaks in humans. the list of cases maintained by the who was restricted to a subset of primary cases based on explicit inclusion and exclusion criteria and was used to analyze the effect of weather on case occurrence using a case-crossover design. all four weather variables demonstrated statistically significant correlations within the incubation period for mers in humans. the statistically significant time lags for each variable do not match up perfectly, which is to be expected and could be due to a number of reasons including natural variability in incubation periods, variable impact of weather on transmission, the interaction of unmeasured cofactors on weather variables as well the direct effect of unmeasured factors on transmission, and stochasticity in general. acute weather events as well as general seasonal patterns may affect disease transmission rates by altering pathogen viability and persistence in the environment as well as by influencing human behaviour and contact patterns. this study found that mers-cov, although a zoonotic disease, follows similar environmental transmission patterns to other non-zoonotic respiratory diseases with analogous modes of transmission such as influenza and respiratory syncytial virus. tamerius et al. [ ] have shown that global trends of influenza broadly follow either a "cold-dry" or "humid-rainy" pattern, corresponding to temperate and tropical climates. additionally, temperate climates tend to have a single annual peak and tropical climates have semi-annual peaks. they further demonstrate that for countries with an annual influenza peak such as saudi arabia, temperature and humidity can be predictive of those peaks, even at latitudes close to the equator. respiratory syncytial virus also follows similar environmental conditions, with peak timing in the arabian peninsula from december to february, following the distribution of cases in the temperate northern hemisphere [ ] . the influence of weather is further supported by experimental evidence, which has demonstrated that lower temperatures and lower relative humidity each favour influenza transmission [ ] . furthermore, coronaviruses have been shown to exhibit strong seasonal variation in natural hosts, and the theory that these fluctuations may increase risk of zoonotic transmission at certain times of the year has been discussed [ ] . the results here demonstrate that colder, drier conditions may increase the risk of zoonotic transmission of mers from dromedaries to humans. sandstorms, dust storms, and air pollution in saudi arabia and elsewhere have been associated with increased morbidity and mortality, including from respiratory disease [ , ] . a case-crossover study in the united states demonstrated the short-term effects of air pollution on acute lower respiratory infections [ ] , while another study demonstrated increased numbers of pneumonia admissions following acute dust storm events in taiwan [ ] . dust storms can act as a pathogen carrier and also induce inflammatory reactions, potentially increasing both exposure and susceptibility to disease agents [ ] . horizontal ground visibility and wind speed were used as proxies for the occurrence of sandstorms and acute air pollution events. visibility can be reduced to m for an average of . h during a sandstorm [ ] . summarizing the weather data used in this study, the mean daily visibility by province ranged from m to over , m, although the median value was over m in all but one province. the distribution of visibility indicates that fig. daily mean and minimum temperature and risk of primary mers by province in saudi arabia. odds ratio (solid line) and % confidence limits (dashed lines) are plotted on the y-axis, while time lags preceding case occurrence are plotted on the x-axis. the odds of primary mers is increased with low temperature at and day lags (a &b), while the odds of primary mers are decreased with high temperatures at and day lags (c & d). asterisks indicate statistically significant odds ratios on corresponding days anything less than full clarity was categorized as low visibility, and that according to the measurements in [ ] , could indicate the presence of a sandstorm. it was hypothesized that primary mers infections are more likely to increase following sandstorms or other severe events of air pollution that affect visibility. however, results indicate that the risk of primary mers infection increased following high visibility days, and decreased following low visibility days. this may be due to behaviour, if people are more likely to stay inside during acute weather events, and less likely to engage in activities such as interacting with camels. it was further hypothesized that higher wind speeds would be associated with more cases of mers. while a positive association was found between cases and high maximum wind speeds days prior, there were also similar results to those of visibility. low minimum wind speed was positively correlated with cases, and conversely, when minimum wind speed was relatively high there were statistically fewer cases of mers. results suggest that further investigation of wind speed as a factor for primary mers is warranted. there are several limitations and potential sources of bias in this study. the major cities in saudi arabia are severely polluted and exceed who guidelines, as measured by particulate matter (pm) [ , ] . sand and dust storms as well as other sources of air pollution such as industrial activities, fuel combustion, and traffic emissions contribute to elevated levels of pm in the country [ ] , all of which contribute to reduced visibility [ ] [ ] [ ] . this study did not differentiate between sandstorms and other acute events that reduce visibility, and discerning between different forms of air pollution may provide insights about the risk of mers-cov transmission under different environmental conditions. fifty-two cases ( . %) in the subset of primary cases had no known exposure history (no information on camel exposure, contact with a known case, nor healthcare worker status). the subset of primary cases investigated likely also include secondary cases, and is a source of selection bias. furthermore, given that mers is an emerging disease, case reporting and data collection standardization may have improved over the -year period included here. geographical case data were available only at the provincial level, while exposure data from the weather station closest to the largest metropolitan city in each province were used. while camel raising in the middle east is moving from extensive to intensive production systems and concentrating around cities [ ] , human spillover cases would be scattered throughout the provinces to an unknown degree. therefore, if environmental conditions differ significantly within a province, this could be a source of misclassification bias. the risk of primary human cases of mers was associated with a decrease in temperature and humidity, and an increase in ground visibility. the temperature and humidity findings are consistent with associations between the environment and other respiratory diseases. further study of weather and seasonal risk factors may strengthen the evidence for an environmental component of mers-cov transmission. a better understanding of virus viability in different environmental conditions is also a key research need. evidence of environmental risk factors for mers could be utilized by public or one fig. daily visibility and wind speed variables and risk of primary mers by province in saudi arabia. odds ratio (solid line) and % confidence limits (dashed lines) are plotted on the y-axis, while time lags preceding case occurrence are plotted on the x-axis. the odds of primary mers is increased with high visibility and decreased with low visibility after days (a & c), while the odds of primary mers are increased with low wind speed and decreased when wind speed is high at -day lags (b & d). when maximum wind speed was high, the odds of a mers case were increased with a -day lag (not shown). asterisks indicate statistically significant odds ratios on corresponding days health practitioners for targeted interventions during higher-risk periods. the risk of mers acquired from zoonotic transmission, or from asymptomatic carriers in the community, appears to be sensitive to weather conditions, providing key initial evidence of an environmental component for the development of primary mers-cov infections. isolation of a novel coronavirus from a man with pneumonia in saudi arabia world health organization. who | middle east respiratory syndrome coronavirus (mers-cov). who world health organization. investigation of cases of human infection with middle east respiratory syndrome coronavirus (mers-cov) interim guidance middle east respiratory syndrome coronavirus (mers-cov) fact sheet mers-cov technical working group. mers-cov: progress in global response to epidemic threat, remaining challenges and way forward: report from the fao-oie-who global technical meeting on mers-cov presence of middle east respiratory syndrome coronavirus antibodies in saudi arabia: a nationwide, cross-sectional, serological study evidence for camel-to-human transmission of mers coronavirus middle east respiratory syndrome world health organization. mers situation update replication and shedding of mers-cov in upper respiratory tract of inoculated dromedary camels influenza virus transmission is dependent on relative humidity and temperature latitudinal variations in seasonal activity of influenza and respiratory syncytial virus (rsv): a global comparative review international approach to environmental and lung health a perspective from the fogarty international center short-term elevation of fine particulate matter air pollution and acute lower respiratory infection lung health in era of climate change and dust storms seasonality of infectious diseases and severe acute respiratory syndrome-what we don't know can hurt us should we use a case-crossover design? a comparison of case-crossover and case-control designs in a study of risk factors for hemorrhagic fever with renal syndrome bias in the case-crossover design:implications for studies of air pollution middle east respiratory syndrome coronavirus (mers-cov) disease outbreak news world health organization. who | middle east respiratory syndrome coronavirus: case definition for reporting to notes from the field: nosocomial outbreak of middle east respiratory syndrome in a large tertiary care hospital national centers for environmental information weathermetrics: functions to convert between weather metrics the case-crossover design: a method for studying transient effects on the risk of acute events referent selection in case-crossover analyses of acute health effects of air pollution reported direct and indirect contact with dromedary camels among laboratory-confirmed mers-cov cases world health organization. who | list of blueprint priority pathogens environmental predictors of seasonal influenza epidemics across temperate and tropical climates the pulmonary consequences of sandstorms in saudi arabia: a comprehensive review and update the effect of sandstorms and air pollution on causespecific hospital admissions in taipei asian dust storm events are associated with an acute increase in pneumonia hospitalization predicting the development of weather phenomena that influence aviation at abu dhabi international airport. pretoria: university of pretoria outdoor particulate matter ( pm ) and associated cardiovascular diseases in the middle east world health organization. who air quality guidelines for particulate matter, ozone, nitrogen dioxide and sulfur dioxide: global update : summary of risk assessment the influence of meteorological conditions and atmospheric circulation types on pm and visibility in tel aviv estimation of particulate matter from visibility in bangkok fine particulate matter characteristics and its impact on visibility impairment at two urban sites in korea: seoul and incheon human-dromedary camel interactions and the risk of acquiring zoonotic middle east respiratory syndrome coronavirus infection the authors would like to thank all of the many individuals who investigated and collected information from mers patients in saudi arabia. availability of data and materials all laboratory confirmed human cases of mers included this publication can be found on the who disease outbreak news website, at the following website: http://www.who.int/csr/don/archive/disease/mers-cov/en/ authors' contributions eg designed the study, analyzed and interpreted the data and wrote the manuscript. ag and dk provided significant guidance in all aspects of the research. ag, dk, svd, mvk and zp substantially contributed to the conception of the study and interpretation of the results, critically reviewed the manuscript and provided final approval for publication.ethics approval and consent to participate not applicable: all data used were publicly available. not applicable. publicly available, non-individually identifying data were used in this publication. the authors declare that they have no competing interests. springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. key: cord- -is odaq authors: al-tawfiq, jaffar a.; memish, ziad a. title: drivers of mers-cov transmission: what do we know? date: - - journal: expert rev respir med doi: . / . . sha: doc_id: cord_uid: is odaq middle east respiratory syndrome coronavirus (mers-cov) emerged in has since resulted in sporadic cases, intra-familial transmission and major outbreaks in healthcare settings. the clinical picture of mers-cov includes asymptomatic infections, mild or moderately symptomatic cases and fatal disease. transmissions of mers-cov within healthcare settings are facilitated by overcrowding, poor compliance with basic infection control measures, unrecognized infections, the superspreaders phenomenon and poor triage systems. the actual contributing factors to the spread of mers-cov are yet to be systematically studied, but data to date suggest viral, host and environmental factors play a major role. here, we summarize the known factors for the diverse transmission of mers-cov. the middle east respiratory syndrome (mers) was initially recognized in and since then a total of cases have been reported from countries, with a case fatality rate of % [ ] . the disease has a wide range of clinical presentation and epidemiology [ ] [ ] [ ] [ ] [ ] . three main factors contribute to the transmission of mers coronavirus (mers-cov): the virus, the host, and the environment. with regard to the patterns of transmission, three patterns have been recognized: sporadic transmission, limited intrafamilial transmission, and healthcare-associated transmissions. here, we review the available data regarding the diversity of transmission and summarize known risk factors for such transmission. one of the reasons for the delayed diagnosis of mers cases is the wide clinical spectrum of mers, which ranges from asymptomatic to mild upper respiratory tract symptoms to acute fulminant pneumonia associated with multisystem failure and death [ ] [ ] [ ] [ ] [ ] . the most common presentations among hospitalized mers patients were fever, cough, shortness of breath, and clinical and radiological evidence of pneumonia [ ] [ ] [ ] [ ] . patients may also present with nonspecific symptoms such as fatigue, myalgia, fever, cough, headache, vomiting, and diarrhea [ ] [ ] [ ] [ ] . patients with severe disease develop respiratory failure secondary to acute lung injury, and may develop renal failure and coagulopathy [ ] [ ] [ ] [ ] [ ] . the case fatality rate is related to the viral load, severity of the disease, and the presence of comorbidities [ ] [ ] [ ] [ ] [ ] . in a recent study, multivariate analysis revealed predictors of mortality as: age > years (odds ratio [or] . ), underlying illness (or . ) , lower c t values where the odds of death increased % for each point drop in c t (or . ) [ ] . the risk of death in patients with mers was significantly associated with age > years ( . times that of younger patients) and treatment for underlying diseases ( . times that of other patients) [ ] . the majority (> %) of the cases of mers infection occur in adults and older adults with one or more comorbidities, and few cases occurred among children [ , ] . comorbidities associated with mers-cov infection include: diabetes mellitus, renal failure, and hypertension, as shown in table [ , , , , ] . the diagnosis of mers-cov infection is based on the detection of viral rna in respiratory samples such as nasopharyngeal swabs, bronchoalveolar wash, or sputum using real-time reverse transcriptase polymerase chain reaction (rt-pcr) assays targeting upe and orf b regions of the mers-cov genome [ , ] . currently, the detection of mers-cov in respiratory samples is considered the gold standard for the diagnosis of mers in a clinical setting. lower or deeper respiratory samples were more likely to be positive for mers-cov than upper respiratory samples and thus these samples are the preferred method of testing using real-time pcr [ , ] . viral loads in lower respiratory samples were at least times more compared to upper respiratory tract samples ( × vs. . × cop/ml, respectively) [ ] . serology using immunofluorescence, serum neutralization, or protein microarray assays adds additional diagnostic methods for the detection of mers-cov antibodies, but most of these tests require a minimum of weeks postinfection to reveal positive results [ , [ ] [ ] [ ] [ ] . different serologic tests were used for the diagnosis of mers-cov infection, which included: plaque reduction neutralization tests (prnts), microneutralization (mn) test, mers-cov-spike pseudoparticle neutralization test (ppnt), and mers-cov s -enzyme-linked immunosorbent assay (elisa) antibody test [ ] . these antibody detection tests (prnt, mn, ppnt, and elisa test) have an excellent sensitivity of - % [ ] . the ppnt does not require biosafety level (bsl)- containment [ ] [ ] [ ] [ ] . in one study, serum dilutions causing plaque reductions of % (prnt ) and % (prnt ) showed that the use of prnt detects few infections that were not detected by prnt tests [ ] . however, these tests were not used for diagnostic purposes, and the exact sensitivity and specificity of mers-cov antibody tests in clinical settings are not known. three main patterns of the transmission of mers-cov are well characterized. these include: sporadic transmission, intrafamilial transmission, and health-care-associated transmissions [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . of all the cases in saudi arabia, % were health-care-associated infections, % were primary cases, and % were among household contacts [ ] . the source of the infection in the remaining % was not reported [ ] . the dynamics of the transmission of mers-cov possibly involves small animals, such as bats, and dromedary camels of africa, with the importation of camels into the kingdom of saudi arabia resulting in subsequent zoonotic transmission. these sporadic cases then lead to intrafamilial transmission and outbreaks in the health-care settings ( figure ). primary cases occurring in the community are thought to be linked to dromedary camels [ , ] . the evidence for dromedary camels as a potential source of infections relies on al-tawfiq et al. [ ] arabi et al. [ ] asiri et al. [ ] shalhoub et al. [ ] assiri et al. [ ] korean cdc [ ] grand total % of the total four different lines of evidence. these lines of evidence are: the high seroprevalence of mers-cov antibodies in dromedary camels, shepherds and abattoir, [ ] [ ] [ ] [ ] as well as similarity in the genome sequences of mers-cov from dromedary and human specimens, [ , [ ] [ ] [ ] [ ] the isolation of mers-cov from camels, [ ] [ ] [ ] and serological evidence that animal infection preceded the human infection in the jeddah case [ , ] . the exact mode of transmission of mers-cov from dromedary camels to humans remains to be elucidated. in a recent case-control study, primary cases were matched to controls [ ] . the answers of the questions for the primary cases were provided by family members in % of instances compared to % in the control group [ ] . in a univariate analysis, the following risks were significant: direct physical contact with a dromedary camel during the last months, household members frequently visited farms with dromedaries, household members had direct contact with dromedaries during the exposure period, dromedaries were present on farm, milked dromedaries while on farm, household members visited a farm with dromedaries during the exposure period, and any direct contact with a dromedary camel during the exposure period [ ] . in a multivariate analysis, risks were associated with direct dromedary exposure in the preceding two weeks, diabetes mellitus, heart disease, and current tobacco smoking [ ] . in june , the investigation of the source of mers-cov around the house of the first patient in bisha showed that a sample from a taphozous perforatus bat (egyptian tomb bat) had % identity to the human mers-cov cloned from the index case-patient [ ] . there are no studies of bats in saudi arabia to further confirm this finding. mers-cov seems to have two seasons for the transmission: march-may and september-november [ ] [ ] [ ] . the reason for the increased cases in april-may was the occurrence of the jeddah outbreak, the associated increase in the number of tests performed, [ ] and increased health-care-associated transmission [ , ] . so increased surveillance identified more cases, although the overall percentage of patients identified did not differ significantly between jeddah ( . %) and other cities ( . %) in the same time period [ ] . in addition, data showed that the seroepidemiology is low in saudi arabia with an overall prevalence of . % of , screened individuals [ ] . any seasonal variation may reflect the risk of transmission of mers-cov between animals and humans, seasonal variation in the circulation of the virus in animals, and the natural reservoirs of mers-cov [ ] . a study evaluating the seasonality of mers-cov transmission showed that mers-cov infections followed influenza a epidemics, and most of the influenza waves did not co-occur with the mers-cov waves [ ] . it is important to study the factors leading to this seasonality of mers-cov, such as parturition of camels. the majority of reported mers cases were secondary cases due to human-to-human transmission. the transmission occurred within family clusters, [ ] [ ] [ ] ] community settings, [ , ] travel-associated transmission, [ ] [ ] [ ] [ ] [ ] and health-care settings [ , , , , [ ] [ ] [ ] [ ] [ ] [ ] [ ] . the transmission within any particular family is also variable and the factors leading to heterogeneity in transmission had not been elucidated. in an outbreak in al-madinah al-munawarah, % were health-care-associated, % were primary cases, and % were among family members [ ] . genomic testing of mers-cov is needed to accompany any cluster investigation to examine the relatedness of the cases to each other. an investigation of a family cluster in hafr al-bain, saudi arabia, indicated that certain cases in the same family were not related to the cluster, but these cases were caused by community transmissions [ ] . the evaluation of contacts of the first mers case was extended to the patient's family contacts, which included three wives, sons, daughters, grandchildren, and one house maid; two shepherds and health-care workers [ ] . none of the contacts was mers-cov-positive by pcr [ ] . the largest data on contact investigation revealed that the percentage of positive cases was . %, . %, and . % among hospital patients, health-care worker contacts, and family contacts, respectively [ ] . thus, the transmission of mers-cov among family members seems to be variable. possible factors leading to heterogeneity in transmissions may include: genetic predisposition, severity of the disease, and other environmental factors. it is clear that health-care-associated infections of mers-cov contribute significantly to the increased number of cases. since , there had been many large outbreaks in the health-care setting involving many facilities. examples of these outbreaks include: al-hasa outbreak, zarqa outbreak in jordan, jeddah, taif, and the republic of korea [ , , , , , , ] . in al-hasa, saudi arabia, confirmed cases and probable cases constituted the outbreak [ ] . further genotyping studies revealed multiple introduction of mers-cov into the hospital outbreak [ ] . between february and april , a multiple health-care-associated mers outbreak took place in jeddah and involved hospitals [ , ] . of all the cases in that outbreak, % of the cases resulted from health-care-associated transmission [ ] . factors contributing to the transmissions and increased number of cases included: sensitive case definition, active search for cases, and contact tracing [ ] . in , a large mers outbreak occurred in the republic of korea [ ] . the outbreak was epidemiologically linked to a single patient who visited multiple countries in the arabian peninsula [ ] . the outbreak resulted the quarantine of , contacts as of july [ ] [ ] [ ] [ ] . and the outbreak resulted in a total of cases and deaths in a short time [ ] . variable intrahospital transmissions occurred among contacts of mers patients. among the contacts of the first case, none of the health-care workers who had significant contact during the patient's stay of days in the private hospital in jeddah were positive [ ] . the described health-care-associated transmissions are driven by multiple factors. these factors include: late recognition, overcrowding, inadequate infection control precautions, prolonged viral shedding, and the occurrence of superspreading events [ ] . the exact definition of a superspreader is not well defined. in one study of sars, a 'superspreading event' was defined as transmission of sars to at least eight contacts, [ ] and others used the term to refer to individuals infecting unusually large numbers of secondary cases [ , ] . a superspreading event was recognized during the sars outbreak when a flight attendant infected more than patients in singapore [ ] [ ] [ ] . in the al-hasa outbreak, a single patient caused seven secondary cases; [ ] thus, a superspreading event may have contributed to the outbreak. the index case in the republic of korea caused secondary cases; one of these cases caused tertiary cases while another patient caused tertiary cases [ ] . in the republic of korea outbreak, superspreaders contributed to the infection of , , , , and from patients' number , , , and , respectively [ ] . another secondary patient resulted in tertiary mers cases, of which % were other patients in the emergency room, and % were health-care workers [ ] . table provides a summary of possible superspreaders in different sars and mers outbreaks [ , , , , , ] . many theories have been given to explain the occurrence of superspreading events and cited factors include the virus characteristics, the host, the environment, and cultural and travel-related behaviors. other contributing factors include: prolonged duration of exposure, the practice of seeking care at multiple health-care facilities, frequent interhospital transfer, and large numbers of contacts [ ] . additional factors include: multi-bedded hospital rooms, crowded hospital rooms, and aerosol-generating procedures [ ] . additional influencing factors include: viral mutation, duration of contact with an infectious host and routes of transmission of infections, genetic susceptibility, and underlying comorbidities [ ] . a higher viral load, more environmental contacts, more interpersonal contacts, and complex network of interactions made by individuals may also play further roles in superspreading events. although initial studies showed that no significant mutation was detected among mers-cov isolates, [ , , ] complete genome analysis of mers-cov showed genetic recombination events between group and group of clade b [ ] . the significance of this recombination in the transmissibility is not known [ ] . many patients with mers have underlying comorbidities [ ] . in one study, % had underlying comorbid medical disorders, including diabetes ( %), hypertension ( %), chronic cardiac disease ( %), and chronic renal disease ( %) [ ] . the viral shedding characteristics in those with comorbid diseases might be different from healthy individuals. after days from the initial positive samples, % of contacts and % of cases were still positive for mers-cov by pcr [ ] . a health-care worker shed mers-cov for about days after initial sample [ ] . environmental persistence of the mers-cov virus was recently investigated. in one study, it was found that mers-cov survives well on surfaces and in the air and that the virus is more stable at low temperature and low humidity conditions [ ] . most of the touchable environments in rooms where mers-cov patients were cared for were contaminated, and viable virus could be isolated in three of the four enrolled patients on days - after symptom onset [ ] . specimens from bed controller and thermometer were pcrpositive until the fifth day from the last positive pcr of the patient's respiratory specimen [ ] . environmental factors contributing to a superspreading event include air recirculation, as occurred in the sars outbreak at the hotel metropole, amoy gardens housing complex, and a flight between china and canada [ ] . the contribution of air recirculation to the spread of mers-cov is yet to be investigated. the custom and behavior of the affected population may also contribute to a superspreading event, and these behaviors include: 'doctor shopping', traditional ways of greetings, hugging and kissing. in the republic of korea outbreak, the presence of many visitors and family members staying with patients contributed to the superspreading event [ ] . hospital environment may also contribute [ ] to the spread of the virus, and these include overcrowding, multi-bedded rooms, and inadequate environmental cleaning. it is estimated that between one-fourth and one-fifth of laboratory-confirmed mers cases are asymptomatic. the exact contribution of asymptomatic individuals and those with prolonged viral shedding to the epidemiology and transmission of mers-cov are not well characterized. a recent survey of patients with laboratory-confirmed mers found that ( . %) were reported as asymptomatic at time of specimen collection; however, when ( %) of those patients were interviewed, ( %) reported at least one symptom that was consistent with a viral respiratory illness [ , ] . it is estimated that between % and % of laboratory-confirmed mers cases are asymptomatic. prolonged viral shedding of patients and asymptomatic contacts pose potential, important challenges for infection control [ ] . mers-cov was detected by rt-pcr for - days from the respiratory tract secretions [ ] . asymptomatic individuals were also described to harbor mers-cov by rt-pcr [ ] . asymptomatic health-care workers shed mers-cov for days from april to june [ ] . since the emergence of mers-cov in , the virus caused sporadic cases, intrafamilial transmission, and major outbreaks in health-care settings. in particular, the transmission within health-care settings is of major concern due to the potential to cause large outbreaks even outside the arabian peninsula. this is exemplified by the large outbreak in the republic of korea. transmissions of mers-cov within health-care settings are facilitated by overcrowding, poor compliance with basic infection control measures, unrecognized infections, the superspreader phenomenon, and poor triage systems. the actual contributing factors to the spread of mers-cov are yet to be systematically studied, but data to date suggest that viral, host, and environmental factors play a major role. understanding these factors and the contribution of each factor to the superspreading events would further enhance the control measures of mers-cov transmission. the epidemiology of the disease was studied in many aspects and showed propensity for the older and those with underlying medical conditions. there is yet an unexplained low rate of involvement of children. the clinical picture of mers had been further elucidated to include asymptomatic infections, mild or moderately symptomatic cases, and fatal disease. this heterogeneity in the clinical presentation is similar to other known infectious diseases and might be related to the immune response. mers-cov is present in the lower respiratory tract system for a prolonged period of time and at higher concentrations than those of the upper respiratory tract, the urine, and the stool. this finding puts the mers-cov dynamics in the same clinical presentation as sars. the finding also has an important role for the prospect of control in health-care settings. in the following years and months to come, it is important to fill the knowledge gap in our understanding of the epide- the authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. this includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. • mers-cov causes sporadic cases, intrafamilial transmission, and nosocomial infections. • mers clinical presentation ranges from mild or asymptomatic cases to severe and fatal disease. • transmission of mers-cov within health-care settings is facilitated by overcrowding, poor compliance with basic infection control measures, unrecognized infections, the superspreader phenomenon, and poor triage systems. • contributing factors for superspreading phenomena include viral, host, and environmental factors. • the virus is present in the lower respiratory tract system for prolonged period of time and at higher concentrations than the upper respiratory tract, the urine, and the stool. family cluster of middle east respiratory syndrome coronavirus infections a family cluster of middle east respiratory syndrome coronavirus infections related to a likely unrecognized asymptomatic or mild case family cluster of middle east respiratory syndrome coronavirus infections mers-cov outbreak in jeddah-a link to health care facilities • an interesting study of one of the largest outbreak in jeddah middle eastern respiratory syndrome corona virus (mers cov): case reports from a tertiary care hospital in saudi arabia epidemiological, demographic, and clinical characteristics of cases of middle east respiratory syndrome coronavirus disease from saudi arabia: a descriptive study •• first study describing the clinical features of mers cases clinical aspects and outcomes of patients with middle east respiratory syndrome coronavirus infection: a single-center experience in saudi arabia middle east respiratory syndrome-coronavirus (mers-cov): a case-control study of hospitalized patients case control study of hospitalized patients with severe acute respiratory illness (sari) molecular epidemiology of hospital outbreak of middle east respiratory syndrome characteristics and outcomes of middle east respiratory syndrome coronavirus patients admitted to an intensive care unit in jeddah, saudi arabia clinical course and outcomes of critically ill patients with middle east respiratory syndrome coronavirus infection outcome of critical mers cases admitted to the intensive care unit hospital outbreak of middle east respiratory syndrome coronavirus • first description of hospital outbreak of mers cases ribavirin and interferon alfa- a for severe middle east respiratory syndrome coronavirus infection: a retrospective cohort study ifn-alpha a or ifn-beta a in combination with ribavirin to treat middle east respiratory syndrome coronavirus pneumonia: a retrospective study association of higher mers-cov virus load with severe disease and death, saudi arabia real-time characterization of risks of death associated with the middle east respiratory syndrome (mers) in the republic of korea middle east respiratory syndrome coronavirus disease in children middle east respiratory syndrome coronavirus not detected in children hospitalized with acute respiratory illness in middle east respiratory syndrome coronavirus outbreak in the republic of korea respiratory tract samples, viral load, and genome fraction yield in patients with middle east respiratory syndrome viral shedding and antibody response in patients with mers-coronavirus infection contact investigation of a case of human novel coronavirus infection treated in a german hospital presence of middle east respiratory syndrome coronavirus antibodies in saudi arabia: a nationwide, cross-sectional, serological study transmission of mers-coronavirus in household contacts occupational exposure to dromedaries and risk for mers-cov infection comparison of serological assays in human middle east respiratory syndrome (mers)-coronavirus infection seroepidemiology for mers coronavirus using microneutralisation and pseudoparticle virus neutralization assays reveal a high prevalence of antibody in dromedary camels in egypt seroepidemiology of middle east respiratory syndrome (mers) coronavirus in saudi arabia ( ) and australia ( ) and characterisation of assay specificity lack of middle east respiratory syndrome coronavirus transmission from infected camels managing mers-cov in the healthcare setting middle east respiratory syndrome coronavirus in healthcare settings an update on middle east respiratory syndrome: years later middle east respiratory syndrome coronavirus infection control: the missing piece? middle east respiratory syndrome coronavirus: transmission and phylogenetic evolution coronaviruses: severe acute respiratory syndrome coronavirus and middle east respiratory syndrome coronavirus in travelers emerging respiratory viral infections: mers-cov and influenza middle east respiratory syndrome-coronavirus infection: an overview saudi ministry of health middle east respiratory syndrome coronavirus in dromedary camels: an outbreak investigation human infection with mers coronavirus after exposure to infected camels, saudi arabia middle east respiratory syndrome (mers) coronavirus seroprevalence in domestic livestock in saudi arabia middle east respiratory syndrome coronavirus (mers-cov) serology in major livestock species in an affected region in jordan antibodies against mers coronavirus in dromedary camels dromedary camels and the transmission of middle east respiratory syndrome coronavirus (mers-cov) middle east respiratory syndrome coronavirus quasispecies that include homologues of human isolates revealed through whole-genome analysis and virus cultured from dromedary camels in saudi arabia middle east respiratory syndrome coronavirus (mers-cov) in dromedary camels mers coronaviruses in dromedary camels mers coronavirus in dromedary camel herd, saudi arabia isolation of mers coronavirus from a dromedary camel evidence for camel-tohuman transmission of mers coronavirus risk factors for primary middle east respiratory syndrome coronavirus illness in humans middle east respiratory syndrome coronavirus in bats, saudi arabia molecular epidemiology and genetic analysis -origin and evolution an observational, laboratorybased study of outbreaks of middle east respiratory syndrome coronavirus in jeddah and riyadh, kingdom of saudi arabia epidemiological findings from a retrospective investigation middle east respiratory syndrome coronavirus (mers-cov): a cluster analysis with implications for global management of suspected cases middle east respiratory syndrome coronavirus (mers-cov) infections in two returning travellers in the netherlands travelrelated mers-cov cases: an assessment of exposures and risk factors in a group of dutch travellers returning from the kingdom of saudi arabia saudi arabia s arabia probable transmission chains of middle east respiratory syndrome coronavirus and the multiple generations of secondary infection in south korea mers outbreak in korea: hospital-to-hospital transmission epidemiological investigation of mers-cov spread in a single hospital in south korea health-care associate transmission of middle east respiratory syndrome corona virus, mers-cov, in the kingdom of saudi arabia health care worker contact with mers patient, saudi arabia hospital-associated outbreak of middle east respiratory syndrome coronavirus: a serologic, epidemiologic, and clinical description multifacility outbreak of middle east respiratory syndrome in taif, saudi arabia community case clusters of middle east respiratory syndrome coronavirus in hafr al-batin, kingdom of saudi arabia: a descriptive genomic study screening for middle east respiratory syndrome coronavirus infection in hospital patients and their healthcare worker and family contacts: a prospective descriptive study transmission and evolution of the middle east respiratory syndrome coronavirus in saudi arabia: a descriptive genomic study middle east respiratory syndrome coronavirus (mers-cov) summary and literature update as of middle east respiratory syndrome coronavirus (mers-cov) -republic of korea south korea coronavirus mers case list -including imported and exported cases middle east respiratory syndrome coronavirus (mers-cov): summary and risk assessment of current situation in the republic of korea and china -as of middle east respiratory syndrome coronavirus (mers-cov). mers-cov in republic of korea at a glance preliminary epidemiological assessment of mers-cov outbreak in south korea middle east respiratory syndrome coronavirus (mers-cov) nosocomial outbreak in south korea: insights from modeling superspreading sars events superspreading and the effect of individual variation on disease emergence an event-based model of superspreading in epidemics role of disease-associated tolerance in infectious superspreaders infectious disease: the tolerance of superspreaders severe acute respiratory syndrome (sars): status of the outbreak and lessons for the immediate future middle east respiratory syndrome coronavirus superspreading event involving persons, korea middle east respiratory syndrome coronavirus (mers-cov) viral shedding in the respiratory tract: an observational analysis with infection control implications complete genome sequence of middle east respiratory syndrome coronavirus kor/knih/ _ _ , isolated in south korea complete genome sequence of middle east respiratory syndrome coronavirus (mers-cov) from the first imported mers-cov case in china origin and possible genetic recombination of the middle east respiratory syndrome coronavirus from the first imported case in china: phylogenetics and coalescence analysis a case of long-term excretion and subclinical infection with middle east respiratory syndrome coronavirus in a healthcare worker stability of middle east respiratory syndrome coronavirus (mers-cov) under different environmental conditions environmental contamination and viral shedding in mers patients during mers-cov outbreak in south korea the role of super-spreaders in infectious disease middle east respiratory syndrome: sars redux? virological and serological analysis of a recent middle east respiratory syndrome coronavirus infection case on a triple combination antiviral regimen key: cord- - tqy tb authors: sheshah, eman; sabico, shaun; albakr, rashed m.; sultan, anmar a.; alghamdi, khalaf s.; al madani, khaled; alotair, hadil a.; al-daghri, nasser m. title: prevalence of diabetes, management and outcomes among covid- adult patients admitted in a specialized tertiary hospital in riyadh, saudi arabia date: - - journal: diabetes res clin pract doi: . /j.diabres. . sha: doc_id: cord_uid: tqy tb this retrospective study aimed to characterize comorbidities and associated with mortality among hospitalized adults with covid- managed as per the saudi ministry of health protocol in a specialized tertiary hospital in riyadh, saudi arabia. medical records of adult patients with pcr-confirmed sars-cov infection and admitted in king salman hospital (ksh) from may to july were included. medical history, management and outcomes were noted. males significantly outnumber females ( versus ). south asians comprise % of all admitted patients. mortality rate was % and highest among saudi males ( . %). type diabetes mellitus (t dm) was the most common comorbidity ( . %). almost all patients ( %) had pneumonia. patients > years were three times more likely to die (confidence interval, ci . - . ; p= . ) from covid- . congestive heart failure (odds ratio or . , ci- . - . ; p= . ) and acute kidney injury (or . , ci- . - . ; p< . ) were significantly associated with higher mortality. dexamethasone use significantly improved the final outcome based on net reclassification improvement (nri) and integrated discrimination improvement (idi) (p< . ). in this single-center study, t dm was very common among hospitalized covid- patients. patients > years, those with congestive heart failure and acute kidney injury are at higher risk for worse covid- outcome. the coronavirus disease global pandemic is an on-going public health catastrophe that has infected more than million individuals and has resulted to more than , casualties as of august , , based on john hopkins university's interactive web-based dashboard to track covid- in real time [ ] . among the gulf cooperation council (gcc) countries, saudi arabia holds the record with the highest number of cases (> , ) and deaths (> ) [ ] . while management of covid- is generally supportive care in nature, different countries do not follow the same protocols and are considered living guidance since they are constantly subject to change. saudi arabia is no different, and hospitals in the country follow the most updated version (july , ) issued by the ministry of health (moh) [ ] . currently, many observational studies have emerged from different countries in identifying risk factors and associations with covid- severity. a consistent risk factor associated with covid- mortality is old age, which has been singled out by both the world health organization (who) and the centers for disease and control (cdc) as the most vulnerable population from covid- [ ] . while this may also be the case for saudi arabia, the country is fortunate to have a relatively young population, but it is also replete with other risk factors associated with old age such as diabetes mellitus (dm), hypertension and obesity [ ] , making the population potentially more susceptible for worse outcomes. another unique feature in saudi arabia, which is also true for the gcc region, is the abundance of migrant labor workers, mostly men, coming less developed countries such as north africa and south asia, the latter of which were recently observed to also have their own share of increasing prevalence of cardiometabolic diseases [ ] . in the first national study on covid- done in the country, . % of the individuals who tested positive from sars-cov were non-saudis [ ] . the heterogeneity, age and health risk burden of the population, as well as the strength of the countries healthcare system, all comes into play when assessing covid- risk factors and prognosis, making such studies' results different geographically. fortunately, and as per the royal decree (issued in march , ) of his royal highness, king salman, free treatment has been provided to all citizens, residents and even residency violators in all saudi hospitals whether public or private to all matters related to covid- [ ] . the present retrospective study aims to determine the common comorbidities and risk factors that are associated with mortality among hospitalized patients admitted for covid- and managed as per the saudi moh protocol for patients suspected of/confirmed with covid- in a single specialized tertiary hospital in the capital riyadh, saudi arabia. the study also aims to determine whether differences exist in presentation, management and outcomes among males and female patients admitted for covid- . this is a single-center, retrospective study done at king salman hospital (ksu), riyadh, saudi arabia. medical records of hospitalized adults from riyadh, saudi arabia who were found to be pcr-positive by nasopharyngeal swab for sars-cov and admitted at ksh from may to july were obtained. those who tested negative for sars-cov , children and without an outcome were excluded. a flowchart has been provided in figure . ethical approval was obtained from the institutional review board (irb) of the college of medicine in king saud university in riyadh, saudi arabia (e- - /aug , ). data obtained included age, nationality, comorbidities, symptoms and vital signs on prior to admission, serological tests done (complete blood count, profiles of liver, renal, glycemic, inflammatory markers and others). management given was based on the guidelines set by the saudi ministry of health protocol for patients suspected of/confirmed with covid- . t dm was based on known medical history and history of anti-dm medication intake. newly diagnosed t dm patients were based on hba c ≥ . and fasting glucose ≥ . mmol/l [ ] . for the purpose of this study, several clinical outcomes were included such as pneumonia (presence of unilateral or bilateral lung infiltrates by chest x-ray), acute respiratory distress syndrome (ards), shock (hypoxic-ischemic damage with dysrhythmias), acute liver injury (elevated liver profile), acute renal injury (elevated renal profile), stroke (abrupt and persistent focal neurologic deficit) and myocardial infarction (abnormal echocardiogram with elevated troponin level). mortality was defined as death as a direct result of covid- infection. final outcome was recorded number of days from hospital admission to final outcome were noted. [ ] at % ci and % power, the required sample size is n= . statistical analysis was done using spss version . (ibm, spss, chicago, il, usa) categorical variables were presented as percentages (%) and continuous variables were presented as mean ± standard deviation (sd) for normal variables and mean ± standard error mean (sem) for non-normal variables. chi-square test was done to determine differences in categorical variables. independent t-test and mann-whitney u-test were done to determine differences between sex and dm status for normal and non-normal variables, respectively. multivariable logistic regression analysis was done to determine odds ratios with % confidence intervals (ci) to determine significant risk factors for outcomes, adjusted for age and sex. likelihood ratio tests was performed using cox regression while area under the curve (auc) was obtained from roc curve. furthermore, the net reclassification improvement (nri) and integrated discrimination improvement (idi) was also obtained using r survidinri package. significance was set at p< . . table shows the general characteristics of hospitalized covid- patients in ksh. males significantly outnumber females by : . all patients were adults with an age-range of - years (mean age . ± . , median age years). female patients were significantly older than males (median age versus years; p< . ). south asians (bangladeshi, pakistani and indian) were the biggest demographic in the cohort with % followed by non-saudi arabs with . % and saudis at . %. south asians were also the biggest group among male patients ( . %) while saudis were the majority among females ( . %). among the comorbidities, t dm was the most common ( . %) followed by hypertension ( . %). this trend was also after stratification for sex. among females however, the prevalence of hypertension was significantly higher than males ( . % versus . %; p< . ). worthy to note is that % (n= ) of the t dm patients were diagnosed on admission. the list of other comorbidities in all patients and after stratification according to sex are seen in table . table shows the presenting symptoms of hospitalized male and female covid- patients. there were no significant differences in the symptoms between sexes. dyspnea ( . %), cough ( . %) and fever ( . %) were the three most common symptoms in seen in overwhelmingly majority of patients. other symptoms such as myalgia ( . %), vomiting ( . %) and diarrhea ( . %) were observed infrequently. among the vital signs, mean temperature on admission was significantly higher in females than males (p= . ). the rest of the vital signs were not significantly different form one another. table displays the biochemical assessments done for the hospitalized male and female patients. mean circulating hemoglobin, alt, ldh and ferritin levels were significantly higher in males than females (p-values . , . , . and . , respectively). majority of patients had abnormal levels in nearly all metabolic markers assessed, including liver and renal and glycemic profile. inflammatory markers in particular (ferritin, crp and troponin) were - times higher than normal (table ) . table shows the management given to hospitalized patients. almost all patients were given lmwh and antibiotics, with all males receiving the latter (p= . ). majority (~ %) also received vitamin c, vitamin d and azithromycin. majority also received hydroxychloroquine ( %) and dexamethasone ( . %). for other treatments, antiviral therapy was given to . % of patients, triple combination therapy was administered in only % of patients and faviperavir in % of cases. in terms of outcome, mortality rate was at % while the rest were discharged. twenty-one patients ( %) required mechanical ventilation. only one out of the hospitalized patients did not develop pneumonia. eleven percent had ards, % had acute liver injury while another . % had acute kidney injury, majority of whom were males (p= . ). only patients developed mi and were both females (p= . ). lastly, the median length of hospital stay was days, ranging from to days. the rest of the outcomes are shown in table . table shows the odds of covid- mortality relative to several risk factors and therapy schemes and adjusted for age and sex. covid- patients above years was almost three times more likely to die (confidence interval, ci . - . ; p= . ) from covid- compared to patients aged below years. among the comorbidities, only congestive heart failure was significantly associated with higher mortality (odds ratio or . , ci- . - . ; p= . ). among the treatment options, patients who were given methylpredinosolone, dexamethasone, hydroxychloroquine and azithromycin were significantly less likely to die from covid- by as much as %, %, % and %, respectively. the rest of the odds ratios are shown in table . a sub-analysis was done focusing only on male patients. figure shows the prevalence of t dm, those above years and mortality rate between saudis and other ethnic groups. saudi nationals had the highest percentage of patients above years ( . %) and mortality rate of . % compared to other ethnic groups (unadjusted p-values . and . , respectively). multinomial logistic regression analysis using death as dependent variable, t dm as independent variable and age as covariate revealed no significance, even after stratification according to ethnicity (not shown in tables). lastly, table shows the results of survival analysis using survidinri package and revealed that the inclusion of dexamethasone was the only factor in the model that significantly improved the outcome as indicated by the significant idi and nri (p< . ). the results were confirmed using changes in auc and the predictive power as indicated by the significant decline in the deviance (∆- loglikelihood). in this retrospective study, characteristics of hospitalized patients with confirmed covid- are presented. these patients were admitted at a specialized tertiary hospital in the capital riyadh, saudi arabia, following the ministry of health's latest protocol for supportive care and treatment of patients suspected of/with confirmed covid- . an overwhelming majority of the patients were males, south asians in particular, while saudis were the predominant in females. the preponderance for males can largely be explained by the cultural set-up in saudi arabia, where females are less socially mobile and home-based, as well as the relatively larger population of men over-all. at a national level however, the number of men infected with sarscov- is only slightly higher than females ( % versus %) [ ] . south asians are a big part of the labor migrants in saudi arabia and the gcc region in general, who, but not all, typically lives in camps provided by their employers [ ] . the crowded living environment of workers prevent them from practicing the needed precautionary distance to avoid risk f sarscov infection, and this could explain why majority of the patients are coming from this demographic group. in the present study, almost all patients had pneumonia, as confirmed by the presence of lung infiltrates in the patients' chest x-rays. fifteen also had elevated random blood glucose levels. whether these patients can be considered as newly diagnosed t dm or non-t dm patients experiencing stressinduced acute hyperglycemia cannot be discerned in the dataset. t dm and hypertension were the most common comorbidities in both males and females, accounting for . % and % of all patients included in the dataset, respectively. these figures are much higher at the national level ( . % and . %, respectively) [ ] and this is expected since the present data set deals only with hospitalized patients with moderate to severe symptoms of covid- . both comorbidities however were not associated with increased likelihood of death. nonetheless, the high prevalence of t dm and hypertension among hospitalized covid- patients have already been observed not only in majority of industrialized countries with high cases of sars-cov infection, but have also been associated with higher risk for severe outcomes, including death [ ] [ ] [ ] . the lack of association to higher odds death in the present study can be partially explained by missing confounders not factored in the model such as bmi and t dm duration, as well as the relatively younger population in the cohort compared to other retrospective studies. two comorbidities in the present study however, the history of congestive heart failure and acute kidney injury in particular, stood out as a significant risk factors for mortality in the present study. this cardiac and renal disorders, together with t dm and hypertension, all belong to a group of vascular endothelial abnormalities that gets exacerbated in the presence of covid- [ ] [ ] . the results of the present study therefore support the on-going theory that it is the underlying endothelial injury present in diseases of the elderly such as t dm and hypertension that is mainly associated with covid- severity and partly explains why the prevalence of such diseases is high among covid- hospitalized patients. another highlight in the present study is the high mortality rate ( %) of the hospital relative to the national mortality rate in saudi arabia which is around . % at the time of this writing. this is expected since only moderate to severe covid- cases are admitted in the hospital and those with no to mild symptoms were advised to self-isolate. separating males alone and stratifying according to ethnicity, saudi men had the highest mortality rate compared to south asians and others, but not statistically significant even before adjusting for age. worthy to mention are the protective effects of corticosteroids (dexamethasone and methylprednisolone) as well as hydroxychloroquine from severe covid- outcomes. hydroxychloroquine in particular protects from covid- death by % in the dataset studied. this percentage, while much higher compared to other recent studies done elsewhere [ ] [ ] [ ] , reiterates that the use of hydroxychloroquine is associated with reduced covid- mortality. several studies however do not consider the use of hydroxychloroquine beneficial for covid- treatment [ ] [ ] . these differences can be partly explained by differences in research methods, some of which were flawed and biased given the premature media attention it received prior to approval [ ] . the use of hydroxychloroquine however in saudi arabia is approved by the ministry of health. the use of corticosteroids on the other hand has been an established treatment for patients with acute respiratory distress syndrome (ards) and other acute lung diseases for immediate immunosuppressive effect, given as either low dose or pulse therapy [ , ] . dexamethasone in particular was the only drug in the present study that significantly improved the final outcome of patients based on nri and idi analysis. this supports the preliminary report of a mega-trial indicating that dexamethasone reduces over-all mortality among patients with covid- [ ] . the authors acknowledge several limitations aside from the retrospective design. as mentioned previously, important confounders such as bmi and t dm duration were not included in medical records. the study therefore cannot ascertain whether obesity is a risk for severe covid- outcome or not, given that obesity is also very prevalent in saudi arabia. other factors such as socio-economic status and medications from existing comorbidities were also not recorded. important parameters such as hba c were present only in a handful of patients. findings cannot be generalized because it is a single center study, and results may not be the same if majority of the patients included were saudi nationals. the study nevertheless is one of the more recent retrospective studies done in saudi arabia focusing on outcomes of hospitalized patients diagnosed with covid- . in summary, the prevalence of t dm is very high and is the most common comorbidity among hospitalized covid- patients in one tertiary hospital in saudi arabia. males outnumber females in hospital admission and majority of patients were of south asian origin. the use of dexamethasone appears to reduce mortality and improve outcome from covid- . larger datasets coming from the different regions in the country are needed to have a better reflection of the true mortality of covid- among hospitalized patients. data available upon request to the joint corresponding author. the authors declare that they have no competing interest. an interactive web-based dashboard to track covid- in real time ministry of health protocol for patients suspected of/confirmed with covid- (version . ) world health organization regional office for europe diabetes mellitus type and other chronic noncommunicable diseases in the central region, saudi arabia (riyadh cohort ): a decade of an epidemic cardio-metabolic disease risk factors among south asian labour migrants to the middle east: a scoping review and policy analysis clinical characteristics of covid- in saudi arabia: a national retrospective study free treatment from coronavirus for all citizens, residents and violators of residency international diabetes federation guideline development group. global guideline for type diabetes diabetes increases the mortality of patients with covid- : a meta-analysis depression in migrant workers and nationals of qatar: an exploratory cross-cultural study features of severe covid- : a systematic review and meta-analysis characteristics of laboratory findings of covid- patients with comorbid diabetes mellitus diabetes and covid- : a systematic review on the current evidences overcoming barriers: the endothelium as a linchpin of coronavirus disease vascular endothelial injury exacerbates coronavirus disease : the role of endothelial glycocalyx protection treatment with hydroxychloroquine, azithromycin, and combination in patients hospitalized with covid- use of hydroxychloroquine in hospitalised covid- patients is associated with reduced mortality: findings from the observational multicentre italian corist study low-dose hydroxychloroquine therapy and mortality in hospitalized patients with covid- : a nationwide observational study of participants outcomes of hydroxychloroquine usage in united states veterans hospitalized with covid- hydroxychloroquine and tocilizumab therapy in covid- patients-an observational study covid- coronavirus research has overall low methodological quality thus far: case in point for chloroquine/hydroxychloroquine mortality in covid- patients with acute respiratory distress syndrome and corticosteroids use: a systematic review and meta-analysis corticosteroids in the treatment of severe covid- lung disease: the pulmonology perspective from the first united states epicenter dexamethasone in hospitalized patients with covid- -preliminary report note: ∆auc and ∆- loglikelihood indicates change in the statistic after the addition of the corresponding independent variable in the model. ** & * indicates p-value < . and < . respectively the authors are also thankful to all nurses and study coordinators at the three study sites who helped in screening of participants, blood and data collection. key: cord- -oi dfsp authors: ahmed, anwar e. title: estimating survival rates in mers-cov patients and days after experiencing symptoms and determining the differences in survival rates by demographic data, disease characteristics and regions: a worldwide study date: - - journal: epidemiol infect doi: . /s x sha: doc_id: cord_uid: oi dfsp although middle east respiratory syndrome coronavirus (mers-cov) has a recorded years of circulation in countries worldwide, there is no international study to assess whether there is variation in mortality by region. neither has there been a comprehensive study detailing how the disease characteristics of mers-cov influence mortality in patients presenting symptoms. this study aimed to assess how region, patient and disease characteristics influence - and -day mortality in mers patients. the author utilised publically available data on mers-cov. the study included mers patients reported between january and march . data on patient and disease characteristics were collected. the mean age at mers-cov diagnosis was . years: . % were male, and . % of the cases were reported from saudi arabia. about % of mers patients studied were over the age of . the study estimated - and -day survival rates after initial onset of symptoms: . % and . %, respectively. saudi arabian mers patients exhibited . and . times higher -day (adjusted hazard risk (ahr) = . ; % confidence interval (ci) . – . ) and -day (ahr = . ; % ci . – . ) mortality risk compared with mers patients in the republic of korea or other countries. similarly, middle eastern mers patients showed . and . times higher -day (ahr = . ; % ci . – . ) and -day (ahr = . ; % ci . – . ) mortality risk compared with mers patients in the republic of korea or other countries. the results demonstrated a link between mortality and geography, disease and patient factors such as regions, symptoms, source of infections, underlying medical conditions, modes of transmission, non-healthcare workers and those of older age. educational programmes, access to healthcare and early diagnosis could be implemented as modifiable factors to reduce the higher mortality rates in mers patients. middle east respiratory syndrome coronavirus (mers-cov) is an international public health challenge with considerable differences in methods of reporting death-related within and between countries [ ] [ ] [ ] [ ] [ ] [ ] [ ] . the case fatality rate accounted for - % in saudi arabia [ ] [ ] [ ] [ ] and - % in the republic of korea [ ] [ ] [ ] . recently, several epidemiological investigations have been published that assessed the factors associated with mortality in mers patients [ ] [ ] [ ] [ ] [ ] [ ] . however, the findings of most of these studies either represent a specific population group such as intensive care unit [ ] , a single medical centre [ ] or outbreak infection in the republic of korea [ , ] . one study analysed publicly available data through the saudi ministry of health webpage to identify the factors associated with mortality in saudi arabian patients [ ] . one limitation of this study was lack of multivariate risk modelling. rivers et al. [ ] used a multivariate poisson regression model to identify factors associated with a high incidence of mortality, but their study excluded all cases ( ) from the republic of korea. a recent study by chen et al. compared the risk factors and disease characteristics in south korean and saudi arabian populations, but did not assess the survival rate in these cases [ ] . the authors of all previously published studies of mers-cov were not able to assess survival rate in mers cases from various countries that were reported to the world health organization (who). although the mentioned studies provided valuable information in terms of mortality risk in mers patients, a common limitation was noted in these previous studies: no global data were used, such as the associations between different geographical regions and mortality. the findings in these reports were made using data on specific populations or regions. per the author's knowledge, at this time there is no large cross-country comparison study of mers-cov-related mortality, and it is not yet clear whether the mortality rate of mers-cov can be identified by countries and regions. it is important to understand and compare mers-cov patients according to their clinical outcomes between multicountries. such a study may provide a useful multi-country work to reduce the mortality in the mers-cov population worldwide. the current study may provide multivariate risk models to identify patients at high risk of death in order to manage mers-cov patient clinical outcomes. this may improve public health plans by establishing effective programmes to prevent serious outcomes. these programmes can be addressed by the healthcare system or public health policies. the goal of this study was to estimate and compare the variations in the risk-standardised mortality rates by regions and by patients' characteristics among different countries across the world, specifically comparing regions that had the largest number of mers-cov cases. the author hypothesised that people of older age, with underlying medical conditions and from saudi arabia or other middle east countries are at high risk of death related to mers-cov. the study utilised a publicly available mers-cov database of case reports retrieved from the who: http://www.who.int/ csr/don/archive/disease/coronavirus_infections/en/. the who receives situational reports of confirmed mers-cov cases from all countries across the globe. the who provides a routine update through its website on new cases, deaths and current developments. prior to january , all reports were presented in a narrative format, describing case by case the disease characteristics of each patient. the author and research assistant accessed each of these narrative reports, and converted the patient information and disease characteristics into a line listing for analysis. beginning with the reporting period of - january, who enhanced their reporting practices, including an excel document with patient and disease characteristic data which can be easily analysed. the latest line listing update of mers cases was on april in a report from qatar. globally, the who report on april indicated that the overall case fatality rate was . % ( deaths of cumulative laboratory-confirmed mers cases) in countries (who, ). the author did not include all mers cases reported to the who because the early reports of mers used unstandardised case presentation that lacked important details. this study included mers cases reported to the who between january and march . another reason for choosing this period to study is that in , the who started reporting cases by the country where the confirmed case has occurred. the author performed quality control checks to detect invalid or missing data. the author excluded some cases from the republic of korea that were reported between june and july , as no patient case report was used. they reported a summary of the updated cases (total cases and deaths) instead of case-by-case details. case # reported on march has been excluded from saudi arabia due to the wrong date of symptom onset stated in his case report. the total cases included in the analysis were . the author obtained information on age, gender, date of notification, date of onset of mers symptoms, date of outcome or death, whether a patient or healthcare worker, symptomatic, underlying medical conditions, source of infection and the reported country. in order to assess the impact of older age on mortality among mers patients, patient age was classified into four groups: age < , - , - and > years. the data retrieved were from countries. the author classified countries into three regions according to the geographical location and the number of cases: ( ) saudi arabia ( . %), ( ) middle east, but excluding saudi arabia ( %), and ( ) republic of korea or other countries ( . %). the republic of korea ( . ) and other countries ( . %) were combined due to the small number of cases in the latter group. saudi arabia was analysed separately from the middle east countries because saudi arabia has a unique situation and recorded the largest number of mers cases. two primary end points were assessed: -and -day mortality related to mersafter developing symptoms. the study author estimated the survival rates using the time of symptom onset to outcome. mers-cov has an incubation period of - days, by which time symptoms usually occur. survival rates at the -day mark are medically significant as they demonstrate survival at the point at which patients most typically experience statistical analyses were performed with sas version . software. data from mers-cov patients who reported to the who between january and march were retrieved and analysed. descriptive statistics were used to describe the study population (table ) . unadjusted cox proportional hazards models (cphms) were used to estimate hazard risk (hr) and a % confidence interval ( % ci) for -and -day mortality (tables and ). multivariable cphms were used to estimate adjusted hazard risk (ahr) and % ci for -and -day mortality adjusting for gender, age, region, whether healthcare worker, having comorbidity, being asymptomatic and the source of infection (tables and ). the log-rank tests were used to compare survival curves for demographic and disease characteristics (figs - ) . the -and -day survival rates were estimated using the kaplan-meier estimator. a total of patients with confirmed mers-cov infection were included in the analysis. the characteristics of the population can be found in table illustrates unadjusted and adjusted -day hazard risks for all-cause mortality. the unadjusted -day analysis shows that age groups - and > years, saudi arabia, the study was conducted to estimate the survival rates in mers patients, specifically and days after experiencing mers-cov symptoms and to determine whether there is a significant epidemiology & infection difference in survival rates by demographic data, disease characteristics and regions using global mers data that were reported to who. the author used the cphms and the kaplan-meier estimator to calculate survival rates. according to the data, the estimated overall survival rate was . % ( % ci . - . %). the study estimated -and -day survival rates were . % ( % ci . - . %) and . % ( % ci . - . %), respectively. the author calculated region-specific -and -day survival rates (figs and ) . for the mers patients studied, the republic of korea or other countries ( . % and . %) had much higher -and -day survival rates than the middle east ( . % and . %) and saudi arabia ( . % and . %), respectively. the differences in the region-specific survival rates remain significant after accounting for patient and disease factors such as gender, age, comorbidity, symptoms, healthcare worker and source of infection. for instance, the hazard of death on -day post-symptoms was . and . times higher in the middle east and saudi arabia compared with the republic of korea or other countries, respectively. the disparities in survival rates between regions are probably explained by the delay in reporting mers symptoms, and consequently delay its diagnosis [ ] . the median time from date of onset of symptoms to death was lower in the republic of korea or other countries than in the middle east and saudi arabia. more research studies are required to assess whether diagnostic delay [ ] and disease characteristics can explain the differences in survival rate by geographical regions. those aged years and older represent a large portion of the mers population ( . %) and they predominantly contribute a high portion of deaths as well. the findings of this study showed that -and -day survival rates tend to rise with increasing age (figs and ) and were similar in women compared with men. the estimate of the -day survival rate in patients older than years was . %, in patients aged - years it was . %, in patients aged - years it was . % and in young patients aged years or less it was . %. these results support various epidemiological cohorts from saudi arabia and the republic of korea, which stated that older age is a risk factor for death in mers patients [ ] [ ] [ ] [ ] [ ] [ ] [ ] . the high death rate among the older age group could be attributable to the greater number of patients with comorbidities in this group. the prevalence of comorbidities increases with age: . % in the young age group < years, . % in - years, % in - years and % in older than years. thus, comorbidities may be associated with both age and mortality. several studies [ ] [ ] [ ] [ ] , including the current study, suggest that the presence of underlying conditions was associated with an increase in the hazard of death in mers patients. more details on underlying conditions are needed to estimate underlying condition-specific survival rates and would be useful to identify which underlying conditions were associated with the lower survival rates. moreover, prevention and disease management strategies should be assessed as interventions in mers patients with underlying conditions to reduce the mortality rate in this group. in concordance with other studies [ , ] , being a nonhealthcare worker was associated with lower survival rates (figs and ) . the study included ( . %) who were healthcare workers, of which five died. the higher survival rates within the healthcare workers group could be attributed to educating healthcare workers on preparedness, access to healthcare or following proper infection control standards. an explanation for lower survival rates in the non-healthcare workers group is the large gaps in public awareness of the clinical symptoms of mers-cov [ , ] . public health and health system interventions are needed to reduce the spread of the mers by raising public awareness in identifying the clinical symptoms and by early screening and diagnosis. this could reduce the high rate of mortality in nonhealthcare workers. patients who had acquired the infection from camels, hospitals and unknown sources of infections exhibited . , . and times higher mortality risk compared with patients who had acquired the infection from a household member, respectively (figs and ). the healthcare system may use this information to properly develop a support care plan to improve patients' outcomes. anwar e. ahmed this study has several limitations. the study used available data on the public source with no details on the underlying conditions. this information could be important to identify which underlying condition is associated with death. patient condition and clinical outcomes may not be final as data are updated routinely. another potential confounding factor was not available, such as access to healthcare, and it may be considered a modifiable factor to account for. finally, an inverse-probability kaplan-meier curve may also be appropriate to model this dataset, as it may provide perspective into the data and a visual way to show adjusted survival rates. despite these limitations, the study author was able to use the estimated -and -day survival rates, measuring the time from symptom onset to outcome. to date, no study has provided survival estimates and links to regions. the study provided information on region-specific and -day survival rates, which are found to account for the differences in mortality. the large sample size used was also the main strength of this study. future study could investigate diagnostic delay, which can be defined by the difference between date of symptom onset and the time of diagnosis. this may reduce poor outcomes. the study estimated -and -day survival rates after initial onset of symptoms: . % and . %, respectively. the results demonstrated a link between mortality and geography, disease and patient factors such as regions, symptoms, source of infections, underlying medical conditions, modes of transmission, non-healthcare workers and older age. educational programmes, access to healthcare and early diagnosis could be implemented as modifiable factors to reduce the higher mortality rates in mers patients. additional files. none. ethical approval and consent to participate. not applicable. consent for publication. the author read and approved the final manuscript. availability of supporting data. the data used for the analysis can be obtained from the study author. declaration of interest. none declared. association of higher mers-cov virus load with severe disease and death, saudi arabia treatment outcomes for patients with middle eastern respiratory syndrome coronavirus (mers cov) infection at a coronavirus referral center in the kingdom of saudi arabia the predictors of -and -day mortality in mers-cov patients predictors of mers-cov infection: a large case control study of patients presenting with ili at a mers-cov referral hospital in saudi arabia estimating the risk of middle east respiratory syndrome (mers) death during the course of the outbreak in the republic of korea high fatality rates and associated factors in two hospital outbreaks of mers in daejeon, the republic of korea middle east respiratory syndrome coronavirus (mers-cov) outbreak in south korea, : epidemiology, characteristics and public health implications presentation and outcome of middle east respiratory syndrome in saudi intensive care unit patients clinical aspects and outcomes of patients with middle east respiratory syndrome coronavirus infection: a singlecenter experience in saudi arabia real-time characterization of risks of death associated with the middle east respiratory syndrome (mers) in the republic of korea mortality risk factors for middle east respiratory syndrome outbreak, south korea risk factors for severity and mortality in patients with mers-cov: analysis of publicly available data from saudi arabia risks of death and severe disease in patients with middle east respiratory syndrome coronavirus comparative epidemiology of middle east respiratory syndrome coronavirus (mers-cov) in saudi arabia and south korea diagnostic delays in symptomatic cases of mers-cov infection in saudi arabia epidemiological, demographic, and clinical characteristics of cases of middle east respiratory syndrome coronavirus disease from saudi arabia: a descriptive study middle east respiratory syndrome coronavirus (mers-cov): prevention in travelers acknowledgements. the author acknowledges the who for making mers-cov data publicly available. no funding was provided for this study.authors' information. college of public health and health informatics, king saud bin abdulaziz university for health sciences, riyadh, saudi arabia. key: cord- - nfukrfl authors: al-ahmadi, khalid; alahmadi, sabah; al-zahrani, ali title: spatiotemporal clustering of middle east respiratory syndrome coronavirus (mers-cov) incidence in saudi arabia, – date: - - journal: int j environ res public health doi: . /ijerph sha: doc_id: cord_uid: nfukrfl middle east respiratory syndrome coronavirus (mers-cov) is a great public health concern globally. although % of the globally confirmed cases have emerged in saudi arabia, the spatiotemporal clustering of mers-cov incidence has not been investigated. this study analysed the spatiotemporal patterns and clusters of laboratory-confirmed mers-cov cases reported in saudi arabia between june and march . temporal, seasonal, spatial and spatiotemporal cluster analyses were performed using kulldorff’s spatial scan statistics to determine the time period and geographical areas with the highest mers-cov infection risk. a strongly significant temporal cluster for mers-cov infection risk was identified between april and may , . most mers-cov infections occurred during the spring season ( . %), with april and may showing significant seasonal clusters. wadi addawasir showed a high-risk spatial cluster for mers-cov infection. the most likely high-risk mers-cov annual spatiotemporal clusters were identified for a group of cities (n = ) in riyadh province between and . a monthly spatiotemporal cluster included jeddah, makkah and taif cities, with the most likely high-risk mers-cov infection cluster occurring between april and may . significant spatiotemporal clusters of mers-cov incidence were identified in saudi arabia. the findings are relevant to control the spread of the disease. this study provides preliminary risk assessments for the further investigation of the environmental risk factors associated with mers-cov clusters. middle east respiratory syndrome coronavirus (mers-cov) is an emerging human viral respiratory infectious disease caused by a novel coronavirus. it was first reported in saudi arabia in [ ] , and since then, it has spread to several other countries, resulting in global public health implications. from april through february , a total of laboratory-confirmed mers-cov cases (with deaths, . %) were reported to the world health organization (who) by countries, with the majority ( cases, . %) being reported by saudi arabia (with deaths, . %) [ ] . the risk assessment of mers-cov infection, transmission and severity is crucial in predicting and preventing further outbreaks of human infections and in enhancing control measures. recent studies have advised that dromedary camels (camelus dromedarius) serve as a reservoir host for mers-cov, and camel-to-human transmission can occur through sporadic zoonotic infections associated with exposure to infected dromedary camels and their products [ ] [ ] [ ] . the risk factors were identified for primary mers-cov infection in persons with either direct or indirect exposure to camels. in particular, higher heterogeneity was more prominent in zoonotic than in human-to-human transmission in the middle east region; this result emphasizes the importance of the environmental component of the epidemic [ ] . although approximately % of the globally reported mers-cov cases are found in saudi arabia, spatial patterns and clusters of the occurrence of this disease have not been addressed, leaving a wide gap in knowledge on this important issue. this study aimed to examine the spatiotemporal clustering of the mers-cov incidence in saudi arabia between and using spatial scan statistics and gis. all laboratory-confirmed mers-cov cases reported between june , and march , were compiled from the official websites of the saudi ministry of health (smoh) [ ] and the who [ ] . we undertook a detailed review of the mers-cov data and performed a range of checks for data consistency, completeness and fitness for the study purpose. we then developed a dataset with variables of interest for each individual with mers-cov. the dataset included the following: diagnosis date, gender, age, nationality, healthcare, employment status and source of infection, as well as the city, governorate and province of residence. a confirmed case is defined as a suspected case that has a laboratory confirmation of mers-cov infection. a suspected case is defined as either (i) an adult patient presenting with severe pneumonia or acute respiratory distress syndrome, based on clinical or radiological evidence, or (ii) an adult patient presenting with an unexplained deterioration of a chronic condition, such as congestive heart failure or chronic kidney disease being treated with hemodialysis, or (iii) a child or an adult patient exposed to a confirmed case of mers-cov or who has visited a healthcare facility where a mers-cov patient was recently identified, or has had a history of contact with dromedary camels or consumption of camel products within days before symptoms and who presents with either (a) acute febrile illness (temperature ≥ • c) with or without respiratory symptoms, or (b) gastrointestinal symptoms and leukopenia or thrombocytopenia. laboratory testing for mers-cov is performed at approved regional smoh and selected non-smoh governmental laboratories to confirm a clinically suspected case and to screen contacts by using validated, commercial, real-time, reverse-transcription polymerase chain reaction (rrt-pcr) assays. the laboratory confirmation of mers-cov infection requires either a positive rrt-pcr result for at least two specific genomic targets, or a region upstream and open reading frame a (upe and orf a) [ ] . a primary case is defined as a person with a laboratory-confirmed mers-cov infection with no evidence of contact with infected individuals but is known or believed to have had direct or indirect exposure to camels or camel habitats. exposure to camels includes direct physical contact with camels or their surroundings (milking and handling excreta), drinking raw camel milk or other unpasteurized products derived from camel milk and handling raw camel meat. indirect contact includes casual contact with sites where camels have been (e.g., camel markets or farms) but without direct physical contact with camels, or living with a household member who has had direct contact with camels. by contrast, a secondary case is defined as a person who has shared the same enclosed space (e.g., a room or office) for frequent or extended periods with an individual with a symptomatic mers-cov infection. mers-cov is believed to spread between humans mainly through contact and respiratory droplets. however, transmission through small particle droplet nuclei (aerosols) may occur. environmental contamination during outbreaks in healthcare facilities can be extensive and might contribute to outbreak amplification, if adequate disinfection procedures are not followed [ ] . the spatial database of the mers-cov incidence in saudi arabia was created in the format of an esri file geodatabase on the three spatial levels of city, governorate and province. saudi arabia consists of administrative provinces, governorates and more than cities. mers-cov cases were grouped and aggregated to be represented by cities, governorates and provinces. the prevalence of intrinsic variance instability in estimating incidence rates as a result of the variation in populations across spatial units, which can possibly identify outliers, has received broad attention in the disease mapping field [ ] . to address this issue, we used geoda [ ] software for generating eb smoothed rate maps for mers-cov incidence. the number of mers-cov incidence cases for the governorates was used as an event variable, and the populations of governorates were estimated from the census [ ] and used as base variables. we analyzed the spatiotemporal clustering of the mers-cov incidence in saudi arabia between and at the city level by using kulldorff's spatial scan statistics via satscan . [ ] . we used purely temporal, seasonal, purely spatial and spatiotemporal retrospective analyses to scan, detect and evaluate the periods and geographical areas with the highest mers-cov risk incidence clusters. the purely spatial scan statistic is defined by a circular window on the map. the window is sequentially centered on each of several possible cities that are positioned throughout the study area. the spatiotemporal scan statistic imposes a cylindrical window with a circular geographic base and height corresponding to time. the temporal scan statistic uses a window that moves in one dimension, time, defined in the same way as the height of the cylinder used by the spatiotemporal scan statistic. the key feature that distinguishes the seasonal scan statistic from the purely temporal scan statistic is that the former ignores the year of the observation and retains only the day and month [ ] . the number of mers-cov cases by city was used as the case file, the city population estimated from the census [ ] was used as the population file and the latitude and longitude of each city were used in the coordinates file. in satscan, an analysis was conducted by progressively scanning a window across time and/or space through a comparison of the number of observed and expected cases of mers-cov incidence, assuming random distribution, inside the window at each city. the null hypothesis is that the incidence of mers-cov is randomly distributed, and the alternative hypothesis is that the incidence increases more inside the window than in areas outside it. the log likelihood ratio (llr) is the hypothesis-testing statistic estimated based on monte carlo randomization. the window with the maximum likelihood ratio is the most likely cluster; that is, it identifies the cluster that is least likely to occur by chance. in addition to the most likely cluster, satscan also designates secondary clusters for purely spatial and spatiotemporal analyses and ranks them in relation to their estimated llr statistic. satscan scans for clusters by using different criteria; the criterion recommended by satscan is the percentage of the population at risk, with a value of % [ ] . we tested the percentage of the population at risk from % to %, and from the result, % performed best; that is, the value of % did not include neighboring cities that have a non-elevated risk. the four types of analyses (purely temporal, seasonal, purely spatial and spatiotemporal) were conducted using the poisson discrete-based model with monte carlo permutations to test for statistical significance. only clusters with significance levels of . and only scans of cities with high rates were reported. for temporal analysis, values of day, month and year were set as the time aggregation units for the daily, monthly and annual clusters, respectively, whereas for the seasonal cluster, month was set. for spatiotemporal analysis, month and year were set for the monthly and annual spatiotemporal analyses, respectively. a total of laboratory-confirmed human mers-cov cases reported in saudi arabia during the period between june , and march , were included in this study. the primary cases accounted for . % (n = ) of the total number of confirmed cases; of these, . % (n = ) involved (direct and indirect) exposure to camels. secondary cases accounted for . % (n = ) of the total number of confirmed cases, whereas missing and unknown cases accounted for . % (n = ) and . % (n = ) of the total number of confirmed cases, respectively. on the incidence of mers-cov infection was mostly reported from riyadh (n = , . %), jeddah (n = , . %) and alahsa governorates (n = , . %), figure . the incidence in wadi addawasir, buraydah, taif, alkharj, najran, madinah and makkah governorates ranged from to cases. these were followed by five governorates in northern saudi arabia (hafr albatin, sakaka, hail, dumat aljundal and tabuk) and two governorates in eastern saudi arabia (alkhubar and dammam) with - cases. for the eb smoothed incidence rate of mers-cov infection, the wadi addawasir governorate showed the highest rate across the country, with . cases per , people ( figure ). dumat aljundal and najran governorates followed with . and . cases per , people, respectively. alkharj, alhinakiyah and afif governorates exhibited an incidence rate in the range of . - . cases per , people. in riyadh, the capital of saudi arabia, the the incidence of mers-cov infection was mostly reported from riyadh (n = , . %), jeddah (n = , . %) and alahsa governorates (n = , . %), figure . the incidence in wadi addawasir, buraydah, taif, alkharj, najran, madinah and makkah governorates ranged from to cases. these were followed by five governorates in northern saudi arabia (hafr albatin, sakaka, hail, dumat aljundal and tabuk) and two governorates in eastern saudi arabia (alkhubar and dammam) with - cases. for the eb smoothed incidence rate of mers-cov infection, the wadi addawasir governorate showed the highest rate across the country, with . cases per , people ( figure ). dumat aljundal and najran governorates followed with . and . cases per , people, respectively. alkharj, alhinakiyah and afif governorates exhibited an incidence rate in the range of . - . cases per , people. in riyadh, the capital of saudi arabia, the incidence rate of mers-cov infection was . cases per , people. in buraydah, alahsa and jeddah governorates, the incidence rates were . , . and . cases per , people, respectively. temporal cluster analysis generated from the spatial scan test identified the years , and , the months of april and may of , and the period from april to may , as the strongly significant clusters of annual, monthly and daily mers-cov incidence, respectively (table ) . seasonal cluster analysis revealed that april and may show strongly significant seasonal clusters of mers-cov incidence (table ) . temporal cluster analysis generated from the spatial scan test identified the years , and , the months of april and may of , and the period from april to may , as the strongly significant clusters of annual, monthly and daily mers-cov incidence, respectively (table ) . seasonal cluster analysis revealed that april and may show strongly significant seasonal clusters of mers-cov incidence (table ) . the results of the purely spatial cluster analysis of mers-cov incidence from to revealed the most significant and secondary clusters at the city level (table and figure ). wadi addawasir in riyadh province had the most likely high-risk cluster, followed by a secondary significant cluster in alkharj and aldilm cities in the same province. spatial clusters in single cities were identified across the country; alhofuf (east), dumat aljundal (north), najran (south), alqunfidhah (southwest), alhinakiyah (west) and buraydah (center) represented the third, fourth, fifth, sixth, seventh and eighth secondary clusters, respectively. the results of the spatiotemporal cluster analysis of mers-cov infection, using years and months as the time aggregates from to , showed significant most likely and secondary clusters in saudi arabia (table ; table and figure ; figure ). spatial variations existed between the annual and monthly spatiotemporal clusters. for the annual spatiotemporal clusters, a group of cities (n = ) located in riyadh province was identified as the most likely high-risk cluster for mers-cov incidence between and . this was followed by a secondary cluster that was found for three cities (jeddah, makkah and taif) in makkah province between and . spatiotemporal clusters in single cities were also observed and varied in space and time across the country. wadi the results of the spatiotemporal cluster analysis of mers-cov infection, using years and months as the time aggregates from to , showed significant most likely and secondary clusters in saudi arabia (table ; table and figure ; figure ). spatial variations existed between the annual and monthly spatiotemporal clusters. for the annual spatiotemporal clusters, a group of cities (n = ) located in riyadh province was identified as the most likely high-risk cluster for mers-cov incidence between and . this was followed by a secondary cluster that was found for three cities in this study, we examined the spatial pattern of mers-cov risk at the governorate level and the temporal, seasonal, spatial and spatiotemporal clustering of mers-cov incidence at the city level over a seven-year period. to the authors' knowledge, this is the first study that aims to analyze the spatiotemporal pattern and clustering of mers-cov in saudi arabia. a total of laboratory-confirmed mers-cov cases were reported in saudi arabia, representing approximately % of the global cases. overall, the majority of mers-cov cases were secondary infections ( . %). this result indicates that secondary infections, either hospital or community acquired, remain a major challenge for the saudi healthcare system in the prevention and control of mers-cov outbreaks, despite the significant improvement in mers-cov surveillance. on the other hand, the primary cases accounted for only . % of the total confirmed cases. although compared with the general population, people in close contact with dromedary camels have a higher risk of developing mers-cov infection via a primary source [ ] [ ] [ ] , our results indicated that only . % of the total primarily infected cases were associated with direct or indirect contact with camels. this result is consistent with previous findings [ ] regarding the ambiguity of primary mers-cov infection transmission. in saudi arabia, camel milk and meat production has increased by . % and . % per year, respectively [ ] . however, intensified animal production has epidemiological consequences, including increased risk of disease. recent trends in saudi arabia have indicated a tendency towards dromedary camel husbandry intensification since the s, as evident in increased production in nearby cities by providing enhanced supplemental diets for the animals and improving camel health management [ , , ] . these areas of intensified camel production are probable hotspots for the transmission and spread of mers-cov. in addition, dealing with camel products, consuming raw unpasteurized milk and conducting slaughter processes have been documented as risk factors for primary mers-cov transmission to humans [ ] . the epidemic curve of mers-cov has varied significantly each year from to , and it has exhibited variance in monthly peaks. a combination of sporadic and epidemic patterns as a result of animal-to-human, human-to-human and unknown exposure was observed. by contrast, the epidemic curve in south korea, where the largest outbreak outside of the arabian peninsula occurred, had a clear nosocomial epidemiological pattern [ ] . purely temporal cluster analyses of mers-cov infection illustrated significant clusters in april and may of . this finding is consistent with previous results [ ] , which showed significant peaks in mers-cov incidence between march and may during a similar period. seasonal cluster analysis identified april and may as a strongly significant seasonal cluster of mers-cov infection. in accordance with our findings, it was reported in [ ] that mers-cov infection occurred markedly in june, followed by may and april, and the lowest rates were seen in january. one possible reason for this trend is the seasonal variations in zoonotic infections in camels during the breeding season [ , ] , when camel farms are considered an important potential source of mers-cov transmission [ ] . moreover, a recent serological study in saudi arabia found a higher risk of mers-cov infection in camels in winter than in summer [ ] . however, the low daily frequency and sporadic cases of mers-cov indicate a reduced likelihood of zoonotic-to-human transmission and increased possibility of human-to-human transmission, which is consistent with other findings [ ] . the main mers-cov outbreaks in and were closely followed by human influenza a epidemics [ ] . no coincidence was found between the peak of influenza occurrence and mers-cov occurrence, which suggests that the seasonal characteristics of mers-cov infections may vary from those of human influenza viral infections. in this study, no epidemics of mers-cov were observed during mass gatherings of pilgrims in the hajj season, which is consistent with previous findings [ ] . this indicates another knowledge gap regarding the mode of transmission that needs further investigation. spatial clusters of mers-cov cases were mainly found in a group of cities in the provinces of riyadh, qassim, hail and najran located on the outskirts of larger deserts, which is the natural habitat for camels. however, significant spatial clusters of mers-cov cases were also reported from small general hospitals in single cities, such as wadi addawasir, dumat aljundal, alhinakiyah and alqunfidhah; in these settings, delays in the isolation of suspected patients, inadequate infection and control measures, and late case diagnosis and management are expected. the annual spatiotemporal high-risk mers-cov clusters occurred mainly in the early periods of the mers-cov epidemic (between and ) in major cities, such as riyadh, jeddah, taif, alhofuf and buraydah, whereas recent clusters (between and ) were observed in relatively small cities, such as dumat aljundal and wadi addawasir. this result can be explained by infection prevention and control practices, which were, to some extent, more effective in major cities than in small cities and remote areas. for the monthly spatiotemporal high-risk mers-cov clusters, the cities of jeddah, makkah and taif were identified as a part of the most likely high-risk mers-cov cluster for april and may of , when the number of cases represented the largest accumulation of cases reported since the beginning of the mers-cov outbreak. the probable source of infection in the majority of the cases in this outbreak was secondary human-to-human transmission in jeddah that took place in healthcare facilities as a result of overcrowding and inadequate infection control measures, rather than a sudden increase in primary cases in the community [ ] . the spatiotemporal cluster detected in riyadh between march and october could be attributed to several outbreaks, with the most prominent one occurring in a single healthcare setting in riyadh in august [ ] . in addition, the most recent clusters of mers-cov incidence were identified in wadi addawasir in february , in dumat aljundal in august and in buraydah in march ; according to [ ] [ ] [ ] , the majority of the cases were associated with healthcare-acquired infections. this indicates persistent challenges related to nosocomial transmission, which require a thorough investigation of compliance to infection control measures by healthcare workers. mers-cov infection has global public health implications and has been labelled as an epidemic in saudi arabia. this study examined the spatial pattern and spatiotemporal clusters of mers-cov incidence in saudi arabia for the first time by using the latest publicly available mers-cov data. the results of this study provide initial risk assessments that can be used as the basis for the further investigation of the potential environmental risk factors that can explain the spatiotemporal clusters of mers-cov infection. the immediate isolation of suspected patients, adequate infection control measures and early case diagnosis and management remain the principal elements in controlling the spread of the disease, especially in small hospitals and in remote areas. future research investigating the effects of age, gender and occupation on mers-cov infection and mortality is needed. isolation of a novel coronavirus from a man with pneumonia in saudi arabia emergencies: middle east respiratory syndrome coronavirus (mers-cov) evidence for camel-to-human transmission of mers coronavirus community case clusters of middle east respiratory syndrome coronavirus in hafr al-batin, kingdom of saudi arabia: a descriptive genomic study global status of middle east respiratory syndrome coronavirus in dromedary camels: a systematic review presence of middle east respiratory syndrome coronavirus antibodies in saudi arabia: a nationwide, cross-sectional, serological study high prevalence of mers-cov infection in camel workers in saudi arabia risk factors for mers-cov seropositivity among animal market and slaughterhouse workers a more detailed picture of the epidemiology of middle east respiratory syndrome coronavirus camel meat in the world peri-urban camel (camelus dromendarius) production system in saudi arabia: a note water, and agriculture in saudi arabia numbering and tracking camels electronically transmission of mers-coronavirus in household contacts middle east respiratory syndrome coronavirus: risk factors and determinants of primary, household, and nosocomial transmission hospital outbreak of middle east respiratory syndrome coronavirus hospital-associated middle east respiratory syndrome coronavirus infections identified transmission dynamics of middle east respiratory syndrome coronavirus infection during an outbreak: implications of an overcrowded emergency department outbreak of middle east respiratory syndrome at tertiary care hospital middle east respiratory syndrome coronavirus transmission in extended family occurrence of the middle east respiratory syndrome coronavirus (mers-cov) across the gulf corporation council countries: four years update risk factors for primary middle east respiratory syndrome coronavirus illness in humans prevalence of comorbidities in cases of middle east respiratory syndrome coronavirus: a retrospective study spatiotemporal frameworks for infectious disease diffusion and epidemiology spatial methods for infectious disease outbreak investigations: systematic literature review mers-cov geography and ecology in the middle east: analyses of reported camel exposures and a preliminary risk map spatial modelling of contribution of individual level risk factors for mortality from middle east respiratory syndrome coronavirus in the arabian peninsula mapping potential amplification and transmission hotspots for mers-cov quantifying spatiotemporal heterogeneity of mers-cov transmission in the middle east region: a combined modelling approach ministry of health in saudi arabia. command and control center world health organization. emergencies preparedness, response. disease outbreaks by year middle east respiratory syndrome coronavirus; guidelines for healthcare professionals. version bayesian disease mapping: hierarchical modeling in spatial epidemiology software for exploratory spatial data analysis (esda) general authority for statistics saudi arabia. the general population and housing census satscan tm v . . software for the spatial and space-time scan statistics guide for version camel sciences and economy in the world: current situation and perspectives systems of camel management in saudi arabia awad-acharari, f. genetic and nongenetic effects for milk yield and growth traits in saudi camels mers-cov in upper respiratory tract and lungs of dromedary camels comparative epidemiology of middle east respiratory syndrome coronavirus (mers-cov) in saudi arabia and south korea a pandemic risk assessment of middle east respiratory syndrome coronavirus (mers-cov) in saudi arabia global seasonal occurrence of middle east respiratory syndrome coronavirus (mers-cov) infection emergence of mers-cov in the middle east: origins, transmission, treatment, and perspectives infection control and mers-cov in health-care workers the prevalence of middle east respiratory syndrome coronavirus (mers-cov) infection in livestock and temporal relation to locations and seasons interhuman transmissibility of middle east respiratory syndrome coronavirus: estimation of pandemic risk differences in the seasonality of middle east respiratory syndrome coronavirus and influenza in the middle east a systematic review of emerging respiratory viruses at the hajj and possible coinfection with streptococcus pneumoniae increase in middle east respiratory syndrome-coronavirus cases in saudi arabia linked to hospital outbreak with continued circulation of recombinant virus response: disease outbreak news: middle east respiratory syndrome coronavirus (mers-cov)-the kingdom of saudi arabia ministry of health saudi arabia world health organization. who mers-cov global summary and assessment of risk this article is an open access article distributed under the terms and conditions of the creative commons attribution (cc by) license the authors wish to express their gratitude to king abdulaziz city for science and technology and king faisal specialist hospital and research centre for supporting this study, as well as the smoh and the who for providing the data. the authors declare no conflict of interest. key: cord- - n sn lk authors: fagbo, shamsudeen f.; garbati, musa a.; hasan, rami; alshahrani, dayel; al‐shehri, mohamed; alfawaz, tariq; hakawi, ahmed; wani, tariq ahmad; skakni, leila title: acute viral respiratory infections among children in mers‐endemic riyadh, saudi arabia, – date: - - journal: j med virol doi: . /jmv. sha: doc_id: cord_uid: n sn lk the emergence of the middle east respiratory syndrome (mers) in saudi arabia has intensified focus on acute respiratory infections [aris]. this study sought to identify respiratory viruses (rvs) associated with aris in children presenting at a tertiary hospital. children (aged ≤ ) presenting with ari between january and december tested for rvs using the seeplex(r) rv kit were retrospectively included. epidemiological data was retrieved from patient records. of the children tested, . % were ≤ year with a male: female ratio of : . viruses were detected in ( . %) children, ( . %) having dual infections: these viruses include respiratory syncytial virus (rsv) ( %), human rhinovirus (hrv) ( . %), adenovirus ( . %), influenza virus ( . %), and parainfluenzavirus‐ ( . %). children, aged – months, were most infected ( . %). lower respiratory tract infections ( . %) were significantly more than upper respiratory tract infection ( . %) (p < . ). seasonal variation of rv was directly and inversely proportional to relative humidity and temperature, respectively, for non mers coronaviruses (nl , e, and oc ). the study confirms community‐acquired rv associated with ari in children and suggests modulating roles for abiotic factors in rv epidemiology. however, community‐based studies are needed to elucidate how these factors locally influence rv epidemiology. j. med. virol. : – , . © wiley periodicals, inc. acute respiratory illnesses (aris) remain a global burden causing nearly million deaths annually. in developing countries, it is the primary cause of death in children < years [liu et al., ] . in saudi arabia, over . million cases of ari presented to emergency departments in [ministry of health, ] . however, much remains unknown of the proportion of these ari aetiologically linked to respiratory viruses. this situation is further complicated by the emergence of the middle east respiratory syndrome coronavirus (mers cov) in saudi arabia in [zaki et al., ] . the global threat posed by mers cov had led to efforts disproportionately focused on defining mers-cov burden while the overall burden (denominator) of respiratory viruses in the country remains largely uncharacterized. a broadened understanding of respiratory viruses having overlapping ecologies and transmission modes should provide more modalities for integrated public health intervention and prevention. previous studies on ari in saudi arabia have largely focused on local and foreign pilgrims visiting makkah and madeenah during the annual hajj pilgrimage [el-sheikh et al., ; balkhy et al., ; alborzi et al., ; mandourah et al., ] . respiratory infections constitute a recognized health burden during hajj [alzeer, ] with pneumonia in pilgrims being a major reason for hospitalization [bukhari and elhazmi, ] . during the hajj season, almost % of documented deaths of pilgrims was due to respiratory illnesses including pneumonia [ministry of health, ] . as the overwhelming majority of the pilgrims are adults and elderly, children are virtually excluded from these studies. giving that foreign pilgrims originate from all over the world, a major limitation with most of these hajjcentered studies is that they are not adequately powered to accurately discriminate between imported and locally acquired respiratory viruses. in , almost million pilgrims performed the hajj; of these, % were from outside the kingdom [ministry of health, ] . additionally, these studies often lacked seasonal or climatic data in their analyses. there have been previous studies conducted on children with ari in the kingdom; most of these studies [al-hajjar et al., ; ghazal et al., ; akhter et al., ; al hajjar et al., ; alanazi et al., ; amer et al., ] have been conducted in riyadh, the country's capital. the city of riyadh is also part of the riyadh province that reported a population of . million in [ministry of health, ] . the few studies reported from elsewhere in the kingdom include those done in abha, taif, and najran [al-shehri et al., ; abdel-moneim et al., ; al-ayed et al., ] . although, most of these studies have been plagued with small sample sizes, one large sized study of children with ari used a qualitative direct immunofluorescence test [alanazi et al., ] ; such tests are insensitive often giving false negative results [uyeki, ] . serological assays have diagnostic limitations in the clinical management of children with ari [henrickson, ] . the requirement of convalescent phase sera to detect a fourfold rise and thus confirm acute infections makes it irrelevant in the management of acutely ill children. however, it is a good tool in retrospective, epidemiologic studies [anderson et al., ; falsey et al., ] . additionally, it has been shown that infants with ari due to respiratory syncytial virus (rsv) usually lack detectable serologic responses [murphy et al., ; hall et al., ] . similarly, it has been the insensitivity of colorimetric or immunofluorescence based antigen assays for rsv, in comparison with molecular diagnostics, has been reported [falsey et al., ; casiano-colon et al., ] . the advent of rapid and highly sensitive multiplex molecular testing platforms overcome the drawbacks of serology and antigenic tests while permitting simultaneous detection of multiple respiratory viruses. this platform was used to detect respiratory viruses in children presenting with ari under climatic conditions prevailing in the riyadh province. the king fahad medial city (kfmc) is an advanced , -bed tertiary health facility located in riyadh, in the central province of saudi arabia. typically, the country usually experiences high temperatures and low precipitation. in riyadh, average winter temperatures dips as low as ˚c; average summer temperatures peak in july at well over ˚c. rainfall often occur between january and may with an annual rainfall of mm [unfccc, ] [zhang et al., ] . extracted cdnas were tested in a -tube reaction according to manufacturer's protocol. primer set a in tube was directed at e/nl , adv and piv - ; primer set b in tube oc /hku , hrv, rsv a and b, and ifla; and contained primer set c tube- at hbov, iflb, hmpv, piv , and hev. a reaction mix consisting of ml of each  rv multiplex primer sets (a, b, and c), ml -methoxypsoralen ( -mop) solution, ml  multiplex master mix (hotstart r taq dna polymerase and dntps included), and ml cdna template with a final volume of ml. mixtures were subjected to a first round of denaturing at ˚c for min and a second round by cycles at ˚c for sec. this was followed by annealing at ˚c for sec and extension at ˚c for sec. lastly, the mixtures were extended at ˚c for min. internal controls included a mixture of all virus clones (positive) and ddh o (negative) [roh et al ; bruijnesteijn van coppenraet et al., ] . the end products were visualized by electrophoresis on a % agarose gels with ethidium bromide staining. the seeplex rv has a limit of detection of copies/ ml. samples positive for iav were tested for h n using a commercial kit (artus infl./h lc/rg rt-pcr kit; qiagen, germany). children with symptoms such as runny nose, nasal or throat congestion, or itchiness of the throat were described as having upper respiratory infections while those with productive cough, shortness of breath, weakness, and fatigue were classified as having lower respiratory infections. riyadh weather data (king khalid internat ional airport) was electronically retrieved from https://weatherspark.com/history/ / /riyadh-saudi-arabia. for statistical analysis, spss (version . , spss inc., chicago, il) was used. specific prevalence for positive cases have been derived from total positive cases in the respective groups and the one-to-one inferences have been drawn at % ci using chi-square analysis and fisher's exact tests as appropriate. all tests were two-tailed and p < . was considered statistically significant. the study was approved by the kfmc institutional review board (irb). a total of , children (mean age- . months; range day to years) were tested, ( . %) were < year with a male to female ratio of : . nasopharyngeal samples represented % of samples analyzed. respiratory viruses were detected in ( %) children, significantly higher in children ( . %) with acute lower respiratory infection (alri) than acute upper respiratory infection (auri) ( . %) (p < . ). as shown in table i , more than a third of the children were diagnosed with bronchiolitis and pneumonia; of these, over % had respiratory viruses detected in their tested respiratory specimens. as shown in table ii , reveal that rsvs were the most detected viruses ( %); this was followed by hrv found in almost % of positive samples. most respiratory viruses were detected in children - months of age. more boys had rsv and hev infections. single infections with rsv, hrv, hmpv, adv, and iflb showed a significant association with age group. half of the children had single infections, while multiple infections occurred in over %, mostly dual infections ( / ; . %). coinfections were significant amongst those aged - months ( . %), months ( . %), and - months ( . %) (p< . ). co-infection rates were similar in children with both alri and auri: . % and . % for dual infections, and . % and . % for triple infections, respectively. viral co-infections in ari cases were predominantly associated with, in descending order, hbov, hev, and adv (p < . ) (fig. ). more than one virus was detected in . % ( out of ) of patients. children with rsv and hrv co-infection required more oxygen therapy and longer length of stay than those rsv mono-infections. the detection of co-infections with more than two viruses was not significant. children with alri had significant infections with rsvs. human coronaviruses- e/nl and oc were detected in < % of the children. a -day-old male infant had quadruple infection with adv, piv , hrv, and rsv. the pandemic h n virus was only detected in an month-old infant. post mers cov emergence in late , children were also screened, according to prevailing ministry of health guidelines, for mer-cov infection in the regional ministry of health lab: all were negative. the frequency of detection of viruses is shown in figure , with rsv, hrv, and adv being the most common in descending order. seasonal variation in the detection of respiratory viruses was observed. for both years, the detection rates of hrv, rsvs, and hmpv were lowest in june, july, and august (fig. a) . for hrv, increase in detection began in september for both years. as shown in figure b , of the two rsv genotypes, rsv a was more frequently detected throughout the year study period with both peaking during the winter months of december and january. no temporal genotype shift in rsv detection pattern was recorded. though hmpv detection was low ( . %; / ) when compared to rsvs and hrv, it was mostly detected between january and march. july, the hottest month during the study period [average temperature of ˚c and ˚c for and , respectively; fig. b ], recorded the least incidence for most respiratory viruses. june, the least humid month in and (fig. a) , was the period when rsv and hrv were least detected (fig. ) . cumulatively, respiratory virus detection was highest in december and lowest in june ( fig. a and b) . this large study population determined the burden of respiratory viruses associated with ari in children over a -year period a multiplex molecular testing platform. with over % of children testing positive for respiratory viruses, more infections were detected than previous studies [akhter et al., ; al hajjar et al., ; alanazi et al., ; bukhari and elhazmi, ] . researchers from a similarly large tertiary care facility based in riyadh undertook a yearlong (between and ) study of , children; using direct antigen testing and shell vial assay as testing platforms, they found respiratory viruses in only . % [akhter et al., ] of them. most ( %, / ) of these children has rsv infection. this high rate was significantly different from that obtained in the present -year study ( % detection for rsv in children positive for respiratory viruses), as well as others [alanazi et al., ; amer et al., ] . similarly, higher detection rates were observed for influenza and parainfluenza viruses when compared to the results from this this study. it was observed that the . % hmpv detection rate in the present study was lower than the . % rate obtained from another study earlier conducted in a similar tertiary health care facility in riyadh [al hajjar et al., ] . although, the earlier study used a lesser advanced version of the seeplex kit, the seemingly increased rate may be due to most of the children tested in the earlier study being immunocompromised. given its effectiveness as demonstrated in this study, multiplex testing platforms such as the seeplex rv ace can be modified to include mers-cov consensus probes. consequently, the augmented ability to simultaneously test a single specimen for mers-cov and other endemic respiratory viruses should diagnostic turnaround time and optimize utilization of limited specimen volume scenarios as may be envisaged in pediatric settings. analyzing limited specimens using monoplex assays may not only preclude detection of untested respiratory viruses, aetiologically unresolved ari quagmires will abound. additionally, such modified platforms have the potential to elicit more epidemiological data on respiratory viruses including mers-cov. in the backdrop of the incessant multidirectional human traffic of residents between countries within the arabian peninsula and as more recently demonstrated by mers-cov transmission events, it may not be impossible that the epidemiology of respiratory viruses in these countries are somewhat inter-related. more detailed research will, however, be needed to elucidate this. comparatively, a study from neighboring oman reported adv being the second most detected virus in children with ari, aged years or younger [khamis et al., ] ; in the present riyadh study, adv infections was associated with age groups - months, - months, - years, and - months in a decreasing order. extending the findings of previous studies that linked seasonal patterns of ari in children with fewer detection rates of respiratory viruses [alanazi et al., ; bukhari and elhazmi, ] or none [ghazal et al., ], this study seasonally correlated the large rv detection rate which showed an inverse and direct relationship with average temperature and humidity, respectively (fig. ) . however, the depicted graphical correlation was obtained while analyzing our data with externally acquired meteorological data. this study has limitations. firstly, its retrospective design may not permit capture of all ari presenting to the facility. secondly, the results obtained may not represent the true burden of ari due to respiratory viruses in children in the community, a limitation shared by other studies. usually, most mild cases of respiratory viral infections are unlikely to seek care at health care facilities with some patients engaging in self-medication. consequently, these cases remain uncaptured by hospital-based studies or surveillance systems. to address this limitation, community based respiratory virus epidemiologic studies are suggested. though such studies are presently lacking in saudi arabia, similar work done elsewhere [lambert et al., b; van der zalm et al., ; chu et al., ; alsaleh et al., ] have yielded valuable epidemiological data. in australia, workers using community centered studies have shown the strong association between child care attendance and the detection of human metapneumovirus and human coronavirus nl in children [lambert et al., ] . they also documented evidence of significant economic impact of ari managed outside health care settings on families; such costs were greater in healthy preschool aged children with influenza infection than those infected with rsv and other respiratory viruses [lambert et al., a] . in the netherlands, researchers showed that respiratory viruses regularly occur in asymptomatic children sampled in the community [van der zalm et al., ] . by including appropriate temporal and climatic data, such studies will further elucidate the transmission dynamics of respiratory viruses in children in community settings in riyadh. additionally, it is possible that the results of such studies may provide collateral data to help understand possible community transmission of mers cov suggested in a recent study [fagbo et al., ] . the technical assistance of nura al ragi, hanan al qudairy, johara al mutairy, and eman al karafi is acknowledged. we also appreciate the assistance of abdul basir pula and roderick mallete with the figures. detection of bocavirus in children suffering from acute respiratory tract infections in saudi arabia etiology of respiratory viral infections using rapid virus isolation methods at a tertiary care center in riyadh, saudi arabia viral etiology of respiratory infections in children in southwestern saudi arabia using multiplex reverse-transcriptase polymerase chain reaction respiratory viruses in children attending a major referral centre in saudi arabia bronchiolitis in abha, southwest saudi arabia: viral etiology and predictors for hospital admission human metapneumovirus and human coronavirus infection and pathogenicity in saudi children hospitalized with acute respiratory illness viruses associated with respiratory tract infections in children attending to the emergency room, king abdulaziz medical city, riyadh, saudi arabia viral etiology of acute respiratory infections among iranian hajj pilgrims nasal swab samples and real-time polymerase chain reaction assays in communitybased, longitudinal studies of respiratory viruses: the importance of sample integrity and quality control respiratory tract infection during hajj epidemiology of respiratory rna viruses in a cohort of hospitalized children in riyadh, saudi arabia microneutralization test for respiratory syncytial virus based on an enzyme immunoassay influenza a common viral infection among hajj pilgrims: time for routine surveillance and vaccination comparison of two commercial molecular assays for simultaneous detection of respiratory viruses in clinical samples using two automatic electrophoresis detection systems viral agents causing acute lower respiratory tract infections in hospitalized children at a tertiary care center in saudi arabia lack of sensitivity of rapid antigen tests for the diagnosis of respiratory syncytial virus infection in adults molecular epidemiology of respiratory syncytial virus transmission in childcare bacteria and viruses that cause respiratory tract infections during the pilgrimage (haj) season in makkah, saudi arabia molecular epidemiology of hospital outbreak of middle east respiratory syndrome diagnosis of respiratory syncytial virus infection: comparison of reverse transcription-pcr to viral culture and serology in adults with respiratory illness acute respiratory tract infections: epidemiological data, guided case management and outcome in a pediatric hospital in riyadh immunity to and frequency of reinfection with respiratory syncytial virus advances in the laboratory diagnosis of viral respiratory disease epidemiology of respiratory virus infections among infants and young children admitted to hospital in oman the cost of community-managed viral respiratory illnesses in a cohort of healthy preschool-aged children community epidemiology of human metapneumovirus, human coronavirus nl , and other respiratory viruses in healthy preschool-aged children using parent-collected specimens parent-collected respiratory specimens-a novel method for respiratory virus and vaccine efficacy research global, regional, and national causes of child mortality: an updated systematic analysis for with time trends since clinical and temporal patterns of severe pneumonia causing critical illness during hajj. bmc infec dis : . ministry of health. . health statistics annual book g/ h. riyadh. saudi arabia: ministry of health effect of age and preexisting antibody on serum antibody response of infants and children to the f and g glycoproteins during respiratory syncytial virus infection comparison of the seeplex reverse transcription pcr assay with the r-mix viral culture and immunofluorescence techniques for detection of eight respiratory viruses second national communication kingdom of saudi arabia influenza diagnosis and treatment in children: a review of studies on clinically useful tests and antiviral treatment for influenza isolation of a novel coronavirus from a man with pneumonia in saudi arabia high incidence of multiple viral infections identified in upper respiratory tract infected children under years of age in key: cord- -wbd s fo authors: shehata, mahmoud m.; gomaa, mokhtar r.; ali, mohamed a.; kayali, ghazi title: middle east respiratory syndrome coronavirus: a comprehensive review date: - - journal: front med doi: . /s - - - sha: doc_id: cord_uid: wbd s fo the middle east respiratory syndrome coronavirus was first identified in and has since then remained uncontrolled. cases have been mostly reported in the middle east, however travel-associated cases and outbreaks have also occurred. nosocomial and zoonotic transmission of the virus appear to be the most important routes. the infection is severe and highly fatal thus necessitating rapid and efficacious interventions. here, we performed a comprehensive review of published literature and summarized the epidemiology of the virus. in addition, we summarized the virological aspects of the infection and reviewed the animal models used as well as vaccination and antiviral tested against it. coronaviruses (cov) became known to cause human disease in the twentieth century. hcov- e and hcov-oc were discovered in the s and shown to cause respiratory infections in humans [ , ] . with the emergence of sars-cov in [ ] , two other human coronaviruses were discovered, hcov nl , hcov hku [ ] . in , a new type of coronavirus was detected as the cause of severe respiratory illness in humans. the first case was a -year-old male from saudi arabia admitted to hospital with acute respiratory illness leading to pneumonia and acute renal failure. the virus initially named as human corona virus-emc [ ] , is currently known as the middle east respiratory syndrome coronavirus (mers-cov) [ ] . classification and nomenclature of mers-cov phylogenetically, mers-cov is a lineage c β coronavirus (β-cov) and is closely related to bat coronaviruses hku and hku . the rooted phylogenetic analysis showed that mers-cov had an amino acid sequence identity less than % to all other known covs [ ] . the virus initially named by many different working groups as novel coronavirus, human coronavirus emc, human b coronavirus c emc, human b coronavirus c england-qatar, human b coronavirus c jordan-n , and b coronavirus england , which represented the places where the first complete viral genome was sequenced (erasmus medical center, rotterdam, the netherlands) or where the first laboratory-confirmed cases were identified or managed (jordan, qatar, and england) was later named as mers-cov by the coronaviruses study groups of ictv [ , , ] . mers-cov is an enveloped virus with a positive sense rna genome. coronavirus genomes range between to kb in size. the complete sequence of hcov-emc- resulted in nucleotides sequence [ ] . coronavirus genomes are polycistronic with large replicase open reading frames orf a and orf b which are subsequently cleaved into or nonstructural proteins (nsps). the region downstream of orf b encode smaller genes including the spike (s), envelope (e), membrane (m), and nucleocapsid (n) structural protein [ ] [ ] [ ] . the functional receptor for mers-cov is the dipeptidyl peptidase (dpp ) which is present on human nonciliated bronchial epithelial cells surfaces [ ] . the dpp protein displays high amino acid sequence conservation across different species, including the sequence that was obtained from bat cells. cell lines susceptibility studies showed that mers-cov infected several human cell lines, including histiocytes as well as respiratory, kidney, intestinal, and liver cells [ ] . the range of tissue tropism in vitro was broader than that for any other known human coronavirus [ ] . mers-cov can also infect nonhuman primate, porcine, bat, civet, rabbit, and horse cell lines all possessing the dpp receptor [ ] . the replication cycle of mers-cov consists of numerous steps as illustrated by lu et al. [ ] . the mers-cov s protein is a class i fusion protein composed of two subunits: the amino n-terminal receptor binding s and carboxyl c-terminal membrane fusion s subunits. the s /s junction is a protease cleavage site which is responsible for membrane fusion activation, virus entry, and syncytium formation. the s c domain contains the receptor binding domain (rbd), and an n domain [ ] . neutralizing monoclonal antibodies against the rbd may inhibit virus entry into cells and receptor-dependent syncytium formation in cell culture, hence vaccines containing the rbd induced high levels of neutralizing antibodies in mice and rabbits [ ] [ ] [ ] . dpp is the cell key functional receptor for the mers-cov s protein [ ] . mers-cov is the first cov that has been identified to use dpp as a receptor [ , ] . dpp has important roles in glucose metabolism, t cell activation, chemotaxis modulation, cell adhesion, and apoptosis [ , ] . the s subunit contains five domains: a fusion peptide, the heptad repeat (hr ) and hr domains, a transmembrane domain, and a cytoplasmic domain, which form the stalk region of s protein that facilitates fusion of the viral and cell membranes [ , ] . the binding of the s subunit to the cellular receptor triggers conformational changes in the s subunit, which inserts its fusion peptide into the target cell membrane to form a six-helix bundle fusion core between the hr and hr domains that approximates the viral and cell membranes for fusion. mers-cov utilizes many pathways for membrane fusion depending on available host proteases, such as transmembrane protease serine protease (tmprss ), trypsin, chymotrypsin, elastase, thermolysin, endoproteinase lys-c, and human airway trypsin-like protease. proteases cleave the s protein into the s and s subunits to activate the mers-cov s protein for endosome-independent host cell entry at the plasma membrane [ ] [ ] [ ] . in addition to the pervious fusion proteases furin has been identified recently to play an essential role in the mers-cov s protein cleavage activation into their biologically active forms [ , ] . after cell entry, the virion particle disassembles to release the nucleocapsid and viral rna into the cytoplasm for expression of viral polyproteins pp a and pp ab. doublemembrane vesicles and convoluted membranes are formed by the attachment of the hydrophobic domains of the mers-cov replication machinery to the limiting membrane of auto-phagosomes [ ] . the viral polyproteins pp a and pp ab are cleaved by papain-like protease and c-like protease into nsp to nsp [ , , ] . these nonstructural proteins form the replication-transcription complex, which regulates transcription and viral protein expression [ ] . after the production of abundant viral rna and structural and accessory proteins, the n protein binds to the genomic rna in the cytoplasm to form the helical nucleocapsid (viral core). the viral core is enveloped by budding through intracellular membranes between the endoplasmic reticulum and golgi apparatus [ ] . the s, e, and m proteins are transported to the budding virion, where the nucleocapsid probably interacts with m protein to generate the basic structure and complexes with the s and e proteins to induce viral budding and release from the golgi apparatus [ ] . mers-cov replication cycle is completed by releasing the progeny virions through the cell membrane via exocytosis pathway. mice mers-cov strain hcov-emc/ was inoculated to three different mouse strains (immunocompetent balb/c mice, s /svev and innate immune-deficient / stat -/mice) intranasally. no significant weight loss was observed and infectious virus could not be detected in the lungs. only moderate pathological lesions were observed in the lungs. hence no viral replication was observed in these strains of mice [ ] . zhao et al. developed a mouse model transduced with a recombinant adenovirus vector expressing hdpp (ad -hdpp ) in lung tissue. inoculation of mers-cov in these mice resulted in mers-cov replication but without mortality. young mice cleared from mers-cov in - days and old mice in - days. perivascular and peribronchial lymphoid infiltration was observed, with progression to an interstitial pneumonia postinfection [ ] . in another study, transgenic mice expressing hdpp were susceptible to mers-cov infection. infectious virus was isolated from lung and brain tissue and weight loss was observed [ ] . pascal et al. developed humanized transgenic mouse. no mortality or clinical signs was observed but interstitial pneumonia and significant lung disease were observed histopathologically, suggesting that humanized dpp mouse is a model for mers-cov infection in which pathological changes resembles mers-cov infection in humans [ , ] . the rhesus macaque was the first animal model used for mers-cov infection as it possessed dpp receptor [ , ] . in infected animals, an increase in respiratory rates, body temperature, cough and reduced appetite was observed with mild to moderate severity. infectious virus isolated only from the lower respiratory tract. viral rna was detected in the conjunctiva, nasal mucosa, tonsils, pharynx, trachea, bronchus and lungs. mild to marked interstitial pneumonia with dark red lesions appeared in lungs. seroconversion of neutralizing antibodies began at dpi and increased in titer with time. the development of a transient pneumonia, rapid replication, and tropism of mers-cov for the lower respiratory tract resembled the severity of the disease observed in humans [ , , ] . similarly, the common marmoset was shown to possess the dpp receptor [ ] . radiographic imaging showed mild to severe bilateral interstitial infiltration and extensive bronchointertitial pneumonia in infected animals. infectious virus was detected in lower and upper respiratory tract tissue and viral rna was detected in nasal mucosa, oropharyngeal swabs, blood, conjunctiva, lymph nodes, gastrointestinal tract, kidney, heart, adrenal gland, liver, spleen, brain and lungs [ ] . inoculation of syrian hamsters and ferrets with mers-cov did not result in infection [ , ] . rabbits may be used as a model to study pathogenesis, transmission, and disease control strategies of mers-cov in vivo as they seroconvert and shed virus after inoculation [ ] . in september , a novel coronavirus infection was noted in promed mail [ ] . the virus was isolated from the sputum of a -year-old saudi male, who was admitted to a hospital with pneumonia and acute kidney injury in june . a few days later, another report appeared describing an almost identical virus detected in a patient in qatar with acute respiratory syndrome and acute kidney injury. the patient had a recent travel history to saudi arabia and then traveled to uk for further medical care [ , , ] . two cases from jordan (april ) were retrospectively diagnosed as mers patients. since that time, more than cases of mers-cov infection have been reported including deaths [ ] . the actual number of cases could be higher than those reported [ ] . an outbreak of more than confirmed cases including deaths occurred in south korea in may and june . the median age of korean cases were years (range: to years), % were men, and % were health care professionals. the index case was a -year-old male who had recently traveled to several countries in the arabian peninsula [ ] . disease control and prevention (cdc), and the ministry of health of saudi arabia (mohsa) as asymptomatic, mild, severely symptomatic, or mortal. cases may be classified into suspected, probable, and confirmed [ , ] . any person with laboratory confirmation of infection with mers-cov irrespective of clinical signs and symptoms is considered as a confirmed case. who criteria for laboratory confirmation require detection of viral rna or acute and convalescent serology. the presence of nucleic acid can be confirmed by positive results from at least two sequence-specific rrt-pcrs or a single sequence-specific rrt-pcr test and direct sequencing from a separate genomic target [ ] . a case confirmation by serological methods requires demonstration of seroconversion in two samples collected at least days apart using at least one screening assay (enzyme-linked immunoassay, immunofluorescence assay) and a neutralization assay. a probable case is defined by the following criteria, a febrile acute respiratory illness as pneumonia or acute respiratory distress syndrome, direct contact with a confirmed mers-cov case and unavailability of mers-cov testing or results being inconclusive for a single inadequate specimen. any person who developed a fever and pneumonia or acute respiratory distress syndrome with a history of travel to countries in or near the arabian peninsula within days before symptom onset or was in contact with a traveler from this region who developed a febrile respiratory illness is considered as a mers-cov suspected case. the who, cdc, and mohsa recommended laboratory diagnostics for mers-cov infection [ , , , , ] . mers-cov cases must be confirmed by at least two positive qrt-pcr tests on two different specific genomic regions or single positive qrt-pcr with a sequence of another positive genome fragment [ ] . the who algorithm for testing mers-cov relies on qrt-pcr and sequencing [ ] . available real-time tests include an assay targeting the rna upstream of the e gene (upe) as a highly sensitive screening assay and three confirmatory assays targeting open reading frames (orf a and b) and/ or n gene. the orf a assay is of equal sensitivity to the upe assay. the orf b assay is less sensitive but is useful for confirmation. these assays are specific for mers-cov and have not shown cross-reactivity with other respiratory human coronaviruses. for sequencing, two target genes, the rna-dependent rna polymerase (rdrp, present in orf b) and n genes are enough to confirm the existence of mers-cov rna in the samples of a patient [ ] . several serologic assays including immunofluorescence assays, protein microarray assay, enzyme-linked immunosorbent assay (elisa) have been developed for the detection of mers-cov antibodies [ , [ ] [ ] [ ] . any positive test by one of these assays should be confirmed with a neutralization assay. single serological result may be valuable for definition of probable case and should be followed by further testing for confirmation of mers-cov infection [ ] [ ] [ ] . incubation period of mers-cov infections was studied by assiri et al. in . the median incubation period was . days ( % ci . - . days) [ ] . in another report from france of a secondary case, a patient who shared a room with an infected patient, the incubation period was estimated at to days [ ] . in the recent outbreak in south korea during may/june , the median incubation period was . days [ ] . who and cdc recommended that individuals that returned from the arabian peninsula and other affected countries must be evaluated for mers-cov infections up to at least days [ ] . clinical features of mers-cov infections range from asymptomatic cases to mildly ill, severe pneumonia, acute respiratory distress syndrome, septic shock and mortal with multi-organ failure (table ) [ , ] . many other clinical features such as gastrointestinal symptoms (anorexia, nausea, vomiting, abdominal pain, diarrhea), pericarditis, and disseminated intravascular coagulation were reported [ , , ] . specific clinical conditions (comorbidities) were apparently proportionate with high severity of mers-cov infections. a study by assiri et al. in saudi arabia showed that of a total of patients with mers-cov infection in , ( %) had underlying clinical conditions, including diabetes mellitus ( %), hypertension ( %), chronic cardiac disease ( %), and chronic kidney disease ( %) [ ] . this high rate of comorbidities must be interpreted with some caution, since diabetes mellitus is common in saudi arabia, and because approximately half of those were part of an outbreak in a hemodialysis unit, where rates of comorbidities might be high due to chronic kidney disease [ , ] . in another study, being on dialysis, diabetes mellitus, and age > years was associated with mortality [ ] . in this study, testing positive for mers-cov in a plasma sample was a predictor of severe outcome [ ] . younger adults and children appeared to be less susceptible to mers-cov infection. only one study described mers-cov infection in children [ ] . all of those children were discovered during contact investigations of older patients. only of children developed symptoms of mers-cov infection. these two children had underlying conditions (cystic fibrosis and down syndrome). the other children were asymptomatic. there are few reports of mers-cov infections in pregnant women. a five-month pregnant female developed vaginal bleeding and abdominal pain after one week, then delivered a stillborn infant [ ] . another case in the united arab emirates was near term phase, she gave birth to an apparently healthy baby, and died after delivery [ ] . mild and asymptomatic mers-cov infections have been reported, a majority of whom were identified among the contacts of patients [ , , ] . in a report from mohsa, more than contacts of patients were screened using qrt-pcr and seven healthcare workers with mers-cov infection were identified, two of whom were asymptomatic and five of whom had mild upper respiratory tract symptoms [ ] . epidemiological and virological studies were conducted in attempts to determine person to person transmission of mers-cov. they studied case clustering in household and hospital outbreaks in the uk, tunisia, italy, and in healthcare facilities in saudi arabia, france, iran, and lately in south korea. those studies provided strong evidence that human-to-human transmission occurs [ , [ ] [ ] [ ] [ ] . the number of contacts infected by individuals with confirmed infections, however, appears to be limited [ ] , except the outbreak of south korea in may/ june , where most cases were secondary and some cases were tertiary infections [ , ] . secondary cases often were milder or symptomless [ ] . possible modes of transmission include droplet and close contact transmission, air borne transmission, and fomite transmission [ ] . the majority of all laboratory-confirmed secondary cases have been associated with healthcare settings [ ] . the majority of cases of jeddah, saudi arabia hospital outbreak during the spring of were acquired through human-to-human transmission due to systematic weaknesses in infection control [ ] . secondary transmission rates were assessed within households and the transmission rate was around %, suggesting that the actual number of infection is greater than reported [ ] . during the outbreak in south korea during may/june , secondary infections were associated with the index case, who was hospitalized from may to may and were tertiary [ ] . the median incubation period was six days for secondary cases and six days for tertiary cases. this outbreak also clearly demonstrated roles of "superspreaders," who may be responsible for a high proportion of cases [ ] . for instance, a single patient infected more than other people while being treated in the emergency room of a hospital in south korea for three days, - may . transmissibility and epidemic potential studies of mers-cov revealed that the reproduction number (r ) of patients infected with mers-cov ranged between . to . [ , ] . the finding of an r < suggests that mers-cov does not yet have pandemic potential. other study suggested that r values might reach to . to . in the absence of infection control [ ] . shedding periods of mers-cov in humans was reported to be long as viruses were detected in lower respiratory samples of symptomatic patients for more than two weeks [ ] . at instances, prolonged shedding for weeks was detected in an asymptomatic healthcare worker. these findings raise concerns that asymptomatic persons could transmit infection to others in a silent manner [ ] . the majority of cases have occurred in saudi arabia and united arab emirates [ ] [ ] [ ] . many cases have also been reported outside the arabian peninsula in north africa, europe, asia, and north america as shown in table . almost all cases reported outside the arabian peninsula had a travel history to it. the first cluster was in october/november in four men of the same family in riyadh, saudi arabia, two of whom died [ ] . the second cluster was reported in jordan in april involving healthcare workers exposed to fatal patients. in addition, seven surviving hospital contacts seroconverted suggesting that they had mers-cov infection [ ] . the third cluster was reported in uk during january/ february . an english resident had a travel history to saudi arabia and pakistan in january, developed a severe respiratory illness, and tested positive for both mers-cov and h n influenza a, and died in march after infecting several contacts [ ] . a cluster of cases of mers-cov was reported in al-hasa in saudi arabia during april . all those cases were directly linked to human to human contact in the same hospital. there were only two confirmed cases of healthcare workers, and three family members were detected by a survey of over household contacts that visited this hospital [ ] . in france, may , an infection of mers-cov was reported in a patient who recently traveled to the united arab emirates. a second case who shared the hospital room with the first case tested positive. the first patient died and the second patient was critically ill. a survey of healthcare workers found no other infections with mers-cov, despite the lack of use of personal protective equipment [ ] . a surge in mers-cov cases was reported in saudi arabia and the united arab emirates during march and april [ , ] . the majority of cases were associated with hospital-based outbreaks jeddah, riyadh, tabuk, and madinah in saudi arabia as well as in al ain, and abu dhabi in united arab emirates. cases included several healthcare workers, visitors, patients, and ambulance staff. person to person transmission was confirmed in > % of cases. the majority of infected health care workers developed mild symptomatic or asymptomatic infection, but about % had severe illness or died [ ] . the recent outbreak of south korea occurred in may . the index case was a man who had recently traveled to bahrain, the united arab emirates, saudi arabia, and qatar [ ] . as of late july , > secondary cases were reported including death and many cases had been reported among household and hospital contacts [ , ] . in china, one case occurred in a man who traveled to china from korea following exposure to two relatives with mers-cov infection [ ] . in spite of reporting of mers-cov infections throughout the year, some evidence on disease seasonality occurred. the first identified cases of mers-cov infection were reported in april and june [ , , ] . a high increase in cases was reported in april and may followed by a surge in case reporting in april and may . increase in case reporting in march to may were attributed to infection from infected young camels [ , ] sources and modes of transmission of mers-cov are still unclear. initially, a bat origin of mers-cov was suggested based on the relation of genome sequences between mers-cov and bat coronaviruses [ ] . cell tropism studies showed that both bat coronavirus hku and mers-cov shared the same cell type receptors, dpp [ , , ] . mers-cov grows readily in several bat-derived cell lines [ ] . there is no evidence for direct or indirect transmission of mers-cov from bats to humans. virological studies performed in europe, africa, and asia, including the middle east, have shown that coronavirus rna sequences are found frequently in bat feces. some of the sequences were closely related to mers-cov sequences [ ] [ ] [ ] . in a survey from saudi arabia, fecal and rectal samples were tested by pcr for mers-cov, many coronaviruses sequences were detected [ ] . most of the detected sequences were unrelated to mers-cov, but one sequence of nucleotide in the rna-dependent rna polymerase (rdrp) gene had a % identity with a mers-cov. this sequence was detected from feces of a taphozous perforatus bat captured near the home of the index saudi patient. uncommon contact of humans with bats indicates that bats are not the intermediate host of mers-cov transmission but may be the reservoir of the virus [ ] . dromedary camels (camelus dromedarus) appear to be the source of mers-cov. other animals like sheep, goats, and cows tested negative to anti-mers-cov antibodies. camel sera from oman, canary islands, and egypt were positive for anti-mers-cov antibodies in about %, %, and > % of the samples respectively [ , , ] . retrospective studies on archived human sera showed no evidence of infection with mers-cov before [ ] , but anti-mers-cov antibodies were detected in archived camel sera in saudi arabia in [ ] , and united arab emirates in [ ] , indicating circulation of mers-cov in camels for many years. bactrian camels in mongolia tested negative for mers-cov antibodies [ ] . serologic studies from around the middle east suggested that camels are one of the sources of mers-cov as > % of adult camels tested positive and had high titers of antibodies. seropositivity was different in juvenile camels and was usually lower than in adults. these results suggested that mers-cov infections in camels occurred in young ages followed by frequent boosting [ , , , ] . camels in other parts of the world, far from the middle east like in europe, australia, and the americas do not have mers-cov antibodies and have no evidence of infection [ ] . table summarizes camel serologic studies. in a study aimed to evaluate virus infectivity and shedding in camels, three adult dromedary camels were inoculated with mers-cov intratracheally, intranasally, and conjunctivally. those camels shed large quantities of virus from the upper respiratory tract and infectious virus was detected in nasal secretions for days post-inoculation and viral rna for up to days post-inoculation [ ] . human infections with mers-cov were linked to camels. the first evidence was a study in saudi arabia in which the mers-cov full genome sequences of isolates from a man with fatal infection and from one of his camels were identical. this patient had a direct contact with his deceased camels some days before the onset of symptoms. these results suggested that mers-cov can infect dromedary camels and can be transmitted from them to humans by direct close contact [ ] . in other studies, phylogenetic analyses of camel and human isolates of the mers-cov genome demonstrated that the viruses were highly identical or in some cases were similar to each other [ , , ] . seroepidemiological studies shown low prevalence of mers-cov antibodies in humans in saudi arabia [ , ] . a survey of individuals representative of the general population of saudi arabia resulted in seropositive subjects ( . %), however, seropositivity increased - folds in camel-exposed individuals [ ] . in a separate report, of camel shepherds and slaughterhouse workers ( . %) tested positive for mers-cov antibodies [ ] . an overview of mers-cov transmission routes is illustrated in fig. . the development of an effective vaccine is critical for prevention of a mers-cov pandemic. some investigators have indicated that the rbd protein of mers-cov s protein is a good candidate antigen as a subunit vaccine. various rbd fragments showed the highest dpp binding affinity and induced the highest-titer of igg ab and neutralizing ab in mice and rabbits [ , , [ ] [ ] [ ] [ ] [ ] . a robust neutralizing antibody response was elicited in balb/c mice against mers-cov after immunization with purified full s protein nanoparticles produced in sf cells infected with specific recombinant baculovirus containing the s gene [ ] or a recombinant human adenoviral vectors (rad or rad ) containing the s or s genes [ , ] . vaccinia ankara was encoded with full s protein and inoculated to balb/c mice that developed high levels of neutralizing antibodies and had induction of humoral and cell-mediated immunity [ , ] . another study using ad -hdpp -transduced balb/c mice immunized with venezuelan equine encephalitis virus replicon particles containing s protein elucidated a reduction of viral titers to nearly undetectable levels and increased neutralizing antibodies [ ] . recently, wang et al. developed two candidate vaccines, a subunit (full s and s protein fraction) and a dna vaccine (full s and s gene in a mammalian vrc vector). the vaccine containing the full s dna and s protein was the most efficacious in mice and rhesus macaques [ ] . using antibodies to deter mers-cov infection appears to have some promise. transfer of sera containing anti-mers-cov-s protein to or seropositive camel sera to ad -hdpp -transduced mice accelerated virus clearance, inhibited virus attachment, and reduced weight loss [ , , ] . recently, corti et al. successfully isolated monoclonal antibodies from serum obtained from a mers-cov survivor after days of infection [ ] . transduced ad -hdpp balb/c mice were immunized with mg/kg of the mab and showed decreased lung [ ] viral titers, no weight loss, and decreased peribronchial lymphoid infiltration [ ] . no approved antivirals for use against mers-cov infection are yet available. the first approach performed when a new unknown virus like mers-cov emerges is testing drugs used as antiviral for similar viruses [ , , ] . type i interferons and ribavirine combination exhibited acceptable results in cell culture and rhesus macaques by decreasing the host inflammatory response, replication of virus, and improved clinical outcome [ , , ] . a human cohort study in saudi arabia showed that treatment with combination of ribavirin and interferon-α b to did not improve clinical outcomes but this may have been due to late treatment or due to the immunocompromised state of the patients [ ] . in a retrospective study of mers-cov infected patients treated with ribavirin and interferon α- a, results showed -day and -day survival was improved by % and % in the treated group as compared to an untreated group [ ] . the second approach is screening of approved drugs with known safety profiles and transcriptional signatures in different cell lines. several drugs, including antiparasitics, neurotransmitters, antibacterials, inhibitors of clathrinmediated endocytosis estrogen receptor, lipid or sterol metabolism, protein processing, and dna synthesis or repair were tested on culture cells [ , [ ] [ ] [ ] [ ] [ ] . lopinavir-ritonavir combined with pegylated interferon and ribavirin therapy showed improved outcomes in infected marmosets [ ] . the third approach involves in vitro inhibition of s protein to block virus entry into host cells using designed antiviral peptides targeting the hr domain of the s subunit of the mers-cov and preventing the interaction between the hr and hr domains required for the formation of the heterologous six-helix bundle in viral fusion core formation [ , ] . other drugs that act as inhibitors for viral proteases and helicase to suppress mers-cov infection were tested [ ] [ ] [ ] [ ] [ ] . other investigators studied inhibition of mers-cov infection by competitive inhibition of dpp cell receptor using compounds such as sitagliptin, vildagliptin, and saxagliptin [ , ] . more than three years have passed since the first detection of mers-cov human infection and the virus, uncontrolled, continues to cause major outbreaks in the middle east. the recent outbreak in korea demonstrated that a single index case can lead to more infections in a short period of time, hence raising questions about the accuracy of the number of cases being reported in the middle east. furthermore, the korean outbreak confirmed the high fatality rate of mers-cov infection as being true rather than overestimated in case only the more severe cases are detected. in all, public health, veterinary health, and research efforts need to be consolidated in order to answer the following high priority questions: -what is the true extent of human infection with mers-cov? -what antivirals and vaccines are to be used in humans? -what infection control measures are needed in healthcare settings to prevent nosocomial outbreaks? -what measures need to be in place in order to prevent zoonotic infections from camels? -is it possible to control the virus in the camel population and if so, how? -are there other animal species involved in the mers-cov transmission cycle? a new virus isolated from the human respiratory tract recovery in tracheal organ cultures of novel viruses from patients with respiratory disease coronavirus as a possible cause of severe acute respiratory syndrome discovery of seven novel mammalian and avian coronaviruses in the genus deltacoronavirus supports bat coronaviruses as the gene source of alphacoronavirus and betacoronavirus and avian coronaviruses as the gene source of gammacoronavirus and deltacoronavirus isolation of a novel coronavirus from a man with pneumonia in saudi arabia middle east respiratory syndrome coronavirus (mers-cov): announcement of the coronavirus study group genomic characterization of a newly discovered coronavirus associated with acute respiratory distress syndrome in humans transmission and evolution of the middle east respiratory syndrome coronavirus in saudi arabia: a descriptive genomic study first confirmed cases of middle east respiratory syndrome coronavirus (mers-cov) infection in the united states, updated information on the epidemiology of mers-cov infection, and guidance for the public nidovirales: evolving the largest rna virus genome virus-encoded proteinases and proteolytic processing in the nidovirales adenosine deaminase acts as a natural antagonist for dipeptidyl peptidase -mediated entry of the middle east respiratory syndrome coronavirus differential cell line susceptibility to the emerging novel human betacoronavirus c emc/ : implications for disease pathogenesis and clinical manifestation human coronavirus emc does not require the sars-coronavirus receptor and maintains broad replicative capability in mammalian cell lines serologic assessment of possibility for mers-cov infection in equids identification of a receptor-binding domain in the s protein of the novel human coronavirus middle east respiratory syndrome coronavirus as an essential target for vaccine development the receptor binding domain of the new middle east respiratory syndrome coronavirus maps to a -residue region in the spike protein that efficiently elicits neutralizing antibodies searching for an ideal vaccine candidate among different mers coronavirus receptor-binding fragments-the importance of immunofocusing in subunit vaccine design dipeptidyl peptidase is a functional receptor for the emerging human coronavirus-emc interspecies transmission and emergence of novel viruses: lessons from bats and birds dipeptidylpeptidase iv from bench to bedside: an update on structural properties, functions, and clinical aspects of the enzyme dpp iv structure-based discovery of middle east respiratory syndrome coronavirus fusion inhibitor structure of the fusion core and inhibition of fusion by a heptad repeat peptide derived from the s protein of middle east respiratory syndrome coronavirus the spike protein of the emerging betacoronavirus emc uses a novel coronavirus receptor for entry, can be activated by tmprss , and is targeted by neutralizing antibodies inhibition of proprotein convertases abrogates processing of the middle eastern respiratory syndrome coronavirus spike protein in infected cells but does not reduce viral infectivity role of the spike glycoprotein of human middle east respiratory syndrome coronavirus (mers-cov) in virus entry and syncytia formation host cell entry of middle east respiratory syndrome coronavirus after two-step, furin-mediated activation of the spike protein furin at the cutting edge: from protein traffic to embryogenesis and disease mers-coronavirus replication induces severe in vitro cytopathology and is strongly inhibited by cyclosporin a or interferon-α treatment middle east respiratory syndrome coronavirus (mers-cov): challenges in identifying its source and controlling its spread crystal structure of the papain-like protease of mers coronavirus reveals unusual, potentially druggable active-site features characterization of the coronavirus m protein and nucleocapsid interaction in infected cells sars-beginning to understand a new virus wildtype and innate immune-deficient mice are not susceptible to the middle east respiratory syndrome coronavirus rapid generation of a mouse model for middle east respiratory syndrome generation of a transgenic mouse model of middle east respiratory syndrome coronavirus infection and disease pre-and postexposure efficacy of fully human antibodies against spike protein in a novel humanized mouse model of mers-cov infection pneumonia from human coronavirus in a macaque model host species restriction of middle east respiratory syndrome coronavirus through its receptor, dipeptidyl peptidase middle east respiratory syndrome coronavirus (mers-cov) causes transient lower respiratory tract infection in rhesus macaques an animal model of mers produced by infection of rhesus macaques with mers coronavirus infection with mers-cov causes lethal pneumonia in the common marmoset the middle east respiratory syndrome coronavirus (mers-cov) does not replicate in syrian hamsters asymptomatic middle east respiratory syndrome coronavirus infection in rabbits novel coronavirus-saudi arabia: human isolate. archive number: . . published date patient with new strain of coronavirus is treated in intensive care at london hospital middle east respiratory syndrome coronavirus (mers-cov)-saudi arabia middle east respiratory syndrome coronavirus: quantification of the extent of the epidemic, surveillance biases, and transmissibility mers-cov in the republic of korea at a glance. . who. laboratory testing for middle east respiratory syndrome coronavirus -interim recommendations (revised) revised case definition for reporting to who-middle east respiratory syndrome coronavirus-interim case definition as of middle east respiratory syndrome (mers), case definition middle east respiratory syndrome coronavirus, case definition for reporting to who, interim case definition as of middle east respiratory syndrome coronavirus (mers-cov): summary of current situation, literature update and risk assessment interim guidelines for collecting, handling, and testing clinical specimens from patients under investigation (puis) for middle east respiratory syndrome coronavirus (mers-cov) assays for laboratory confirmation of novel human coronavirus (hcov-emc) infections laboratory testing for middle east respiratory syndrome coronavirus cross-reactive antibodies in convalescent sars patients' sera against the emerging novel human coronavirus emc ( ) by both immunofluorescent and neutralizing antibody tests contact investigation of a case of human novel coronavirus infection treated in a german hospital specific serology for emerging human coronaviruses by protein microarray transmission of mers-coronavirus in household contacts seroepidemiology for mers coronavirus using microneutralisation and pseudoparticle virus neutralisation assays reveal a high prevalence of antibody in dromedary camels in egypt laboratory testing for middle east respiratory syndrome coronavirus epidemiological, demographic, and clinical characteristics of cases of middle east respiratory syndrome coronavirus disease from saudi arabia: a descriptive study che d; investigation team. first cases of middle east respiratory syndrome coronavirus (mers-cov) infections in france, investigations and implications for the prevention of human-to-human transmission preliminary epidemiological assessment of mers-cov outbreak in south korea update: severe respiratory illness associated with middle east respiratory syndrome coronavirus (mers-cov)-worldwide family cluster of middle east respiratory syndrome coronavirus infections clinical features and viral diagnosis of two cases of infection with middle east respiratory syndrome coronavirus: a report of nosocomial transmission is mers another sars? ifn-α a or ifn-β a in combination with ribavirin to treat middle east respiratory syndrome coronavirus pneumonia: a retrospective study middle east respiratory syndrome coronavirus disease in children cov investigation team stillbirth during infection with middle east respiratory syndrome coronavirus middle east respiratory syndrome coronavirus infections in health care workers mers-cov outbreak in jeddah-a link to health care facilities hospital outbreak of middle east respiratory syndrome coronavirus presence of middle east respiratory syndrome coronavirus antibodies in saudi arabia: a nationwide, cross-sectional, serological study world health organization global outbreak alert and response network middle east respiratory syndrome coronavirus international investigation team. family cluster of middle east respiratory syndrome coronavirus infections spread of mers to south korea and china summary and risk assessment of current situation in republic of korea and china notice to health care providers: updated guidelines for evaluation of severe respiratory illness associated with middle east respiratory syndrome coronavirus (mers-cov) epidemiological investigation of mers-cov spread in a single hospital in south korea interhuman transmissibility of middle east respiratory syndrome coronavirus: estimation of pandemic risk assessing the pandemic potential of mers-cov evidence for camel-to-human transmission of mers coronavirus a case of long-term excretion and subclinical infection with middle east respiratory syndrome coronavirus in a healthcare worker update on the epidemiology of middle east respiratory syndrome coronavirus (mers-cov) infection, and guidance for the public, clinicians, and public health authorities middle east respiratory syndrome middle east respiratory syndrome coronavirus (mers-cov): summary of current situation, literature update and risk assessment-as of hospital-associated outbreak of middle east respiratory syndrome coronavirus: a serologic, epidemiologic, and clinical description severe respiratory illness caused by a novel coronavirus middle east respiratory syndrome coronavirus (mers-cov) mers coronavirus in dromedary camel herd, saudi arabia seroepidemiology of middle east respiratory syndrome (mers) coronavirus in saudi arabia ) and characterisation of assay specificity rooting the phylogenetic tree of middle east respiratory syndrome coronavirus by characterization of a conspecific virus from an african bat middle east respiratory syndrome coronavirus in bats, saudi arabia human betacoronavirus c emc/ -related viruses in bats, ghana and europe close relative of human middle east respiratory syndrome coronavirus in bat the lancet infectious diseases. need for global cooperation in control of mers-cov middle east respiratory syndrome coronavirus (mers-cov) serology in major livestock species in an affected region in jordan koopmans mp. middle east respiratory syndrome coronavirus neutralising serum antibodies in dromedary camels: a comparative serological study investigation of anti-middle east respiratory syndrome antibodies in blood donors and slaughterhouse workers in jeddah and makkah, saudi arabia, fall antibodies against mers coronavirus in dromedary camels absence of mers-coronavirus in bactrian camels, southern mongolia mers coronavirus neutralizing antibodies in camels mers coronaviruses in dromedary camels middle east respiratory syndrome coronavirus in dromedary camels: an outbreak investigation middle east respiratory syndrome (mers) coronavirus seroprevalence in domestic livestock in saudi arabia middle east respiratory syndrome coronavirus antibody reactors among camels in dubai geographic distribution of mers coronavirus among dromedary camels antibodies against mers coronavirus in dromedary camels replication and shedding of mers-cov in upper respiratory tract of inoculated dromedary camels middle east respiratory syndrome coronavirus infection in dromedary camels in saudi arabia lack of mers coronavirus neutralizing antibodies in humans, eastern province, saudi arabia intranasal vaccination with recombinant receptor-binding domain of mers-cov spike protein induces much stronger local mucosal immune responses than subcutaneous immunization: implication for designing novel mucosal mers vaccines potent neutralization of mers-cov by human neutralizing monoclonal antibodies to the viral spike glycoprotein a truncated receptor-binding domain of mers-cov spike protein potently inhibits mers-cov infection and induces strong neutralizing antibody responses: implication for developing therapeutics and vaccines a safe and convenient pseudovirus-based inhibition assay to detect neutralizing antibodies and screen for viral entry inhibitors against the novel human coronavirus mers-cov tailoring subunit vaccine immunity with adjuvant combinations and delivery routes using the middle east respiratory coronavirus (mers-cov) receptor-binding domain as an antigen purified coronavirus spike protein nanoparticles induce coronavirus neutralizing antibodies in mice immunogenicity of an adenoviral-based middle east respiratory syndrome coronavirus vaccine in balb/c mice systemic and mucosal immunity in mice elicited by a single immunization with human adenovirus type or vectorbased vaccines carrying the spike protein of middle east respiratory syndrome coronavirus middle east respiratory syndrome coronavirus spike protein delivered by modified vaccinia virus ankara efficiently induces virus-neutralizing antibodies protective efficacy of recombinant modified vaccinia virus ankara (mva) delivering middle east respiratory syndrome coronavirus spike glycoprotein evaluation of candidate vaccine approaches for mers-cov passive immunotherapy with dromedary immune serum in an experimental animal model for middle east respiratory syndrome coronavirus infection prophylactic and postexposure efficacy of a potent human monoclonal antibody against mers coronavirus inhibition of novel β coronavirus replication by a combination of interferon-α b and ribavirin cyclophilins as modulators of viral replication broad-spectrum antivirals for the emerging middle east respiratory syndrome coronavirus treatment with interferon-α b and ribavirin improves outcome in mers-cov-infected rhesus macaques ribavirin and interferon therapy in patients infected with the middle east respiratory syndrome coronavirus: an observational study ribavirin and interferon α- a for severe middle east respiratory syndrome coronavirus infection: a retrospective cohort study cell host response to infection with novel human coronavirus emc predicts potential antivirals and important differences with sars coronavirus antiviral potential of erk/mapk and pi k/akt/mtor signaling modulation for middle east respiratory syndrome coronavirus infection as identified by temporal kinome analysis testing of middle east respiratory syndrome coronavirus replication inhibitors for the ability to block viral entry screening of an fda-approved compound library identifies four small-molecule inhibitors of middle east respiratory syndrome coronavirus replication in cell culture interferon-β and mycophenolic acid are potent inhibitors of middle east respiratory syndrome coronavirus in cell-based assays treatment with lopinavir/ritonavir or interferon-β b improves outcome of mers-cov infection in a nonhuman primate model of common marmoset prediction and biochemical analysis of putative cleavage sites of the c-like protease of middle east respiratory syndrome coronavirus assessing activity and inhibition of middle east respiratory syndrome coronavirus papain-like and c-like proteases using luciferase-based biosensors evaluation of ssya - as a replication inhibitor of severe acute respiratory syndrome, mouse hepatitis, and middle east respiratory syndrome coronaviruses thiopurine analogs and mycophenolic acid synergistically inhibit the papain-like protease of middle east respiratory syndrome coronavirus the newly emerged sars-like coronavirus hcov-emc also has an "achilles' heel": current effective inhibitor targeting a c-like protease inhibition of middle east respiratory syndrome coronavirus infection by anti-cd monoclonal antibody mahmoud m. shehata, mokhtar r. gomaa, mohamed a. ali, and ghazi kayali declare that they have no conflict of interest. this manuscript is a review article and does not involve a research protocol requiring approval by the relevant institutional review board or ethics committee.