Middle East Respiratory Syndrome Coronavirus Transmission Marie E
Total Page：16
File Type：pdf, Size：1020Kb
PERSPECTIVE Middle East Respiratory Syndrome Coronavirus Transmission Marie E. Killerby, Holly M. Biggs, Claire M. Midgley, Susan I. Gerber, John T. Watson (Figure). MERS-CoV human cases result from primary Middle East respiratory syndrome coronavirus (MERS- or secondary transmission. Primary transmission is CoV) infection causes a spectrum of respiratory illness, classified as transmission not resulting from contact from asymptomatic to mild to fatal. MERS-CoV is transmitted sporadically from dromedary camels to humans with a confirmed human MERS case-patient 15( ) and can and occasionally through human-to-human contact. result from zoonotic transmission from camels or from Current epidemiologic evidence supports a major role in an unidentified source. Conzade et al. reported that, transmission for direct contact with live camels or humans among cases classified as primary by the WHO, only 191 with symptomatic MERS, but little evidence suggests (54.9%) persons reported contact with dromedaries (15). the possibility of transmission from camel products or Secondary transmission is classified as transmission asymptomatic MERS cases. Because a proportion of case- resulting from contact with a human MERS case- patients do not report direct contact with camels or with patient, typically characterized as healthcare-associated persons who have symptomatic MERS, further research is or household-associated, as appropriate. However, needed to conclusively determine additional mechanisms many MERS case-patients have no reported exposure to of transmission, to inform public health practice, and to a prior MERS patient or healthcare setting or to camels, refine current precautionary recommendations. meaning the source of infection is unknown. Among 1,125 laboratory-confirmed MERS-CoV cases reported iddle East respiratory syndrome (MERS) coro- to WHO during January 1, 2015–April 13, 2018, a total Mnavirus (MERS-CoV) was first detected in Sau- of 157 (14%) had unknown exposure (15). 1 di Arabia in 2012 ( ). To date, >2,400 cases globally Although broad categories of exposure are have been reported to the World Health Organiza- associated with transmission (e.g., exposure to camels tion (WHO), including >850 deaths (case fatality rate or to healthcare facilities with ill patients), exact ≈ 2 35%) ( ). Illness associated with MERS-CoV infec- mechanisms of MERS-CoV transmission are not fully tion ranges from asymptomatic or mild upper respi- understood. Little direct epidemiologic evidence ratory illness to severe respiratory distress and death. exists regarding transmission routes or the efficacy MERS-CoV is a zoonotic virus, and dromedary of interventions in reducing transmission. However, 3 5 camels are a reservoir host ( – ). Bats are a likely other potentially important factors, including original reservoir; coronaviruses similar to MERS- detection of virus in different secretions, detection and 6 CoV have been identified in bats ( ), but epidemiologic survival of virus in the environment, and detection evidence of their role in transmission is lacking. of virus in aerosols, lend support for the biological Infection of other livestock species with MERS-CoV plausibility of certain transmission pathways. 7 is possible ( ); however, attempts to inoculate goats, We summarize the available evidence regarding sheep, and horses with live MERS-CoV did not camel-to-camel, camel-to-human, and human-to- 8 produce viral shedding ( ), and no epidemiologic human transmission of MERS-CoV, including direct evidence has implicated any species other than epidemiologic evidence and evidence supporting dromedaries in transmission. biologically plausible transmission routes. Sporadic zoonotic transmission from dromedaries has resulted in limited human-to-human transmission MERS-CoV in Camels chains, usually in healthcare or household settings (9–14) Evidence for Infection of Camels Author affiliation: Centers for Disease Control and Prevention, MERS-CoV infection in camels has been demon- Atlanta, Georgia, USA strated through serologic investigations, molecular DOI: https://doi.org/10.3201/eid2602.190697 evidence using real-time reverse transcription PCR Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 26, No. 2, February 2020 191 PERSPECTIVE Figure. Summary of Middle East respiratory syndrome coronavirus transmission pathways. Solid lines indicate known transmission pathways; dashed lines indicate possible transmission pathways for which supporting evidence is limited or unknown. (rRT-PCR), and by virus isolation, as described in introduced via calf saliva or nasal secretions or fecal recent reviews (16,17). Geographically wide-ranging contamination. Experimentally introduced virus can seroprevalence studies have identified MERS-CoV– survive in milk but did not survive when heat treated specific antibodies in camels in countries across the (28). It is also not known if the virus would remain vi- Middle East and North, West, and East Africa, often able in milk from seropositive dams when antibodies with >90% seroprevalence in adult camels (18). Stud- could be found in the milk. ies in many of these countries have shown molecular These shedding data indicate that contact with evidence of MERS-CoV RNA and isolation of infec- camel nasal secretions, saliva, and respiratory tious MERS-CoV in camels (16,17,19–21). droplets carry potential risk for camel-to-human or camel-to-camel transmission. Contact with Viral Shedding in Camels nasal secretions can occur when directly handling In naturally or experimentally infected camels, live camels, and virus from camel nasal secretions MERS-CoV appears to cause an upper respiratory can contaminate fomites in the environment (29). tract infection with or without symptoms, includ- Although rRT-PCR evidence of MERS-CoV and ing nasal and lachrymal discharge, coughing, sneez- genome fragments have been detected in air samples ing, elevated body temperature, and loss of appetite from a camel barn (30), no live virus was detected, (20,22,23). In naturally infected camels, MERS-CoV and no epidemiologic study has implicated airborne RNA has been recovered most commonly from na- transmission. Transmission following exposure to sal swabs but also from fecal swabs, rectal swabs, camel feces may be biologically plausible, although and lung tissue (20,24). No evidence of viral RNA has no epidemiologic evidence indicates the likelihood of been demonstrated in camel serum, blood, or urine such transmission. Similarly, although transmission using rRT-PCR (25,26). In experimentally infected following consumption of raw camel milk may camels, infectious virus and RNA was detected in na- be biologically plausible, epidemiologic studies sal swab and oral samples but not in blood, serum, fe- have not consistently identified milk consumption ces, or urine (23). MERS-CoV RNA has been detected as a unique risk factor for MERS-CoV infection in raw camel milk collected using traditional milking or illness, independent of other direct or indirect methods, including using a suckling calf as stimu- camel exposures (31,32). No epidemiologic evidence lus for milk letdown; presence of live virus was not supports transmission associated with camel urine evaluated (27). Viral RNA may therefore have been or meat. 192 Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 26, No. 2, February 2020 MERS-CoV Transmission Camel-to-Camel Transmission Dynamics including age, smoking, handwashing after camel MERS-CoV RNA is detected most frequently in contact, consuming camel meat or milk, or specific younger camels (22,25,33) but has been detected in occupation (camel truck driver, handler, or herder) camels >4 years of age (22). In a longitudinal study of (47). Neither investigation controlled for possible a camel dairy herd, most calves became infected with confounding risk factors (e.g., age or duration of MERS-CoV at 5–6 months of age, around the time ma- exposure to camels). In Abu Dhabi, an investigation ternal MERS-CoV antibodies wane. The calves then of 235 market and slaughterhouse workers showed produced MERS-CoV antibodies by 11–12 months of that 17% were seropositive for MERS-CoV and that age (34). In seroprevalence studies, camels <2 years of daily contact with camels or their waste, working as a age demonstrated lower seroprevalence than camels camel salesman, and self-reported diabetes were risk >2 years of age (25,35). Across many countries, the se- factors for seropositivity (32). Among market workers roprevalence of adult camels is >90% (16,17). Overall, in the same study, handling live camels and either these data suggest most camels are initially infected cleaning equipment (e.g., halters, water troughs, etc.) with MERS-CoV at <2 years of age. However, camels or administering medications to camels were risk can shed virus despite preexisting MERS-CoV anti- factors on multivariable analysis (32). These studies bodies, suggesting that repeat infections are possible generally support the hypothesis that direct physical (36,37). Varying prevalence of MERS-CoV RNA in contact with camels is a risk factor for transmission, camels has been reported in different countries and although cleaning equipment could also result in settings, such as farms (33) and live animal markets indirect transmission. (38). Risk for camel-to-camel or camel-to-human transmission may be influenced by crowding, mix- Potential Seasonality of Human Cases ing of camels from multiple sources, transportation, Previous findings suggest that MERS-CoV circula- and characteristics