Investigating the ecology and animal origins of MERS-CoV

Investigating the ecology and animal origins of MERS-CoV Jonathan H. Epstein, DVM, MPH Kevin J. Olival, PhD EMERGING VIRAL DISEASES THE ONE HEALTH CONNECTION INSTITUTE OF MEDICINE-FORUM ON MICROBIAL THREATS 18-19 MARCH 2014 Local conservation. Global health.

MERS Timeline April 2012 June 13 2012 June 24 2012 Sep 29 2012

Novel MERS-like CoV from bats in Mexico Anthony et al. (2013) J. of Gen Virology

Unaizah Riyadh Bisha

First Known Case - Bisha 60 year old male Admitted to Bisha hospital June 2012 No underlying disease No history animal exposure camels at household sheep at workplace Bats around household and workplace No known secondary cases

Evidence for MERS CoV in camels Oman: 100% (n=50) Spain: 14% (n=105) seropos. (2013), no sheep or goats pos. 1 Qatar: 21% (n=14) camels PCR positive on farm with human case. (2013) 2 UAE: 100% (n=151) in 2003 and 60% (n=651) in 2013 seropos (2014) 3 Egypt: 94% (110) seropos. (no sheep, goats, cows +-ive) 4 Photo: EcoHealth Alliance copyright 2014 KSA: 90% (310) seropos (2010-13) 5 1. Reuskin et al. 2013; 2. Haagmans et al. 2013 3. Meyer et al. 2013 4. Perera et al. 2013 5. Hamida et al. 2013

MERS in Dromedary Camels in KSA 1992-2013 Seroprevalence 1992-2010 Adults : 91%-100% (n=187) Juveniles: 72%-76% (n=77) 2013: 74% seropositive (n=203) Highest in Eastern region Photo: EcoHealth Alliance copyright 2014 RNA detection: 35% juveniles (104) 15% adults (98) Overall = 51/202 = 25% Mostly nasal swabs Highest in western region Goats and sheep neg for MERS Photo: EcoHealth Alliance copyright 2014 Alagaili et al. mbio 2014

Diversity in KSA camel sequences 11 Aligaili et al. mbio 2014

KSA camel imports/exports 1961-2011 Data source: FAOStat Epstein et al, unpublished. 1992: Earliest evidence of MERS infection in KSA camels

Potential for human cases prior to 2012 2013 RNA detection rate: Overall = 51/202 = 25% If 232,652 camels were imported in 2005 with 25% infected, 58,740 infected camels imported. 1 2005 camel population = 272,700 @25% prevalence, 68,175 infected Photo: EcoHealth Alliance copyright 2014 2005 male pop = 13,762,000. 1 camel/50 men Camel herdsman are high risk group Human exposures prior to 2012 likely Photo: EcoHealth Alliance copyright 2014 1. FAO Stat. Epstein et al, unpublished

Conclusions Bats are a likely reservoir for MERS CoV MERS CoV infection widespread in camels MERS CoV in dromedary camels for 20+ years in KSA Camel trade may explain viral diversity and persistence in population More epidemiological data needed to understand whether camel to human transmission occurs

Ecological and Evolutionary Approaches to Understand: Frequency and timing of MERS spillover Wildlife-livestock-human transmission Seasonality of MERS shedding in reservoir Geographic range of host species and spillover potential Intervention strategies to prevent future spillover events

Nipah virus Understanding spillover Malaysia 1998-99 Bangladesh 2001-14

Intermediate Host Not Necessary e.g. SARS-like CoVs Ge et al. 2013, Nature

Human-Animal Interface Bats observed roosting inside human dwellings in KSA during study by Memish et al. 2013. Need to better characterize bat-livestock interface and bat ecology in the region Is there ongoing transmission between bats and camels? Direct transmission between bats or other wildlife and humans (e.g. SARS CoV)?

Seasonality of Viral Shedding? Seasonal CoV shedding in bats linked to reproduction Drexler et al. 2011, EID

Frequency and timing of MERS-CoV spillover events? c. 2011 Camel seqs in RED Human seqs in Black Source: A. Rambaut - http://epidemic.bio.ed.ac.uk

Taphozous spp. and Dromedary Camel Geographic Ranges Potential bat hosts in the genus Taphozous are distributed widely across Africa, the Middle East, South and Southeast Asia, and Australia Areas of overlap with dromedary camels occur across parts of this range, including northern Africa, the Middle East and Australia Surveillance should include regions where both bat and camel hosts occur and potential for spillover exists

MERS CoV Surveillance in SE Asia (Thailand) Training and surveillance workshop with Thailand government, Mahidol University, Chulalongkorn University, Zoological Parks Organization, Department of National Parks, and EcoHealth Alliance (Feb 2014). Photos: EcoHealth Alliance copyright 2014

Additional Wildlife/Domestic Animal Reservoir Species? Clues from Lab Eckerle et al. 2014, EID

MERS Study Acknowledgements EcoHealth Alliance: Peter Daszak, Billy Karesh, Ariful Islam Columbia University CII: W. Ian Lipkin, Nishay Mishra, Vishal Kapoor, Simon Anthony, Lorenzo Ucellini, Amit Kapoor, Thomas Briese, Komal Jain KSA Ministry of Health: Ziad Memish, Shamsudeen Fagbo, Abdulkareem Duro, Mushabab Alasmary King Saud University: Aziz Aligali, Osama Mohammed Population and trade data: FAO Stats FUNDING: