MERS-CoV: Extent of infection in &

transmission to humans

Maria Van Kerkhove, PhD

Center for Global Health, Institut Pasteur, Paris

ESCAIDE 13 November 2015

MERS-CoV: What we know

>1611 cases reported from 26 countries, >575 deaths

Epidemiology of MERS-CoV

Sustained transmission

in humans

Sustained transmission in animals,

not sustained in humans

Human case Detected case

Cross-species transmission Within-species transmission

Animal case

(L) Reuskin et al EID 2014; (R) Ferguson & Van Kerkhove 2014

• Pattern of the epidemic: repeated sporadic introductions into the human population from direct or indirect contact with dromedary camels (and possibly other not-yet identified animals), resulting in limited human-to-human transmission, notably in healthcare settings

• No cases associated with religious pilgrimages

• There is no evidence of sustained human-to-human transmission

• Failures in infection control and prevention in healthcare settings has resulted in large numbers of secondary cases

• Weak evidence for bats and no evidence of MERS-CoVin other animals– Partial sequence found in bat in Saudi Arabia near

location of human case

• Ample evidence that camels play an important role in transmission in the region – Virus has been detected in dromedary camels in:

• Qatar, Saudi Arabia, UAE, Oman and Egypt

– Antibodies have been found in camels in:

• Jordan, Tunisia, Ethiopia, Nigeria, Egypt, Oman, Kenya, Saudi Arabia, Canary Islands, UAE…

– Human and camel viruses closely related

• Significance– MERS-CoV is widespread in camels throughout region

– Transmission is occurring from infected dromedary camels to human

Origins and reservoir

Memish et al EID 2013

Emergence and transmissibility

• Phylogenetics

– More human and animal genetic sequences are becoming available

– Likely emergence mid 2012 though possible similar virus circulating in animals for decades

– Genetic data support multiple introductions into human populations

• Transmissibility of MERS-CoV

– R0 is likely <1*

– Significant heterogeneity in R

– Higher attack rates in specific settings, e.g., health care settings

R0=reproduction number: the average number of secondary cases generated from 1 case at the start of an epidemic*Brenan et al 2013; Cauchemez et al 2014

Cotton et al 2014

What we don’t know….

Unknown 1:

What is the extent of human infection with MERS-CoV?Why 2012? Why such a high proportion of cases from KSA?

Surveillance for MERS

• Significant variation in surveillance for MERS-CoV within and outside of the Middle East– Testing uneven between countries

– Testing uneven over the course of the year

– Noncompliance with surveillance recommendations from WHO

• Notable increases in efforts to monitor for MERS during Hajj– To date, not a single case associated with Hajj (or Umrah)*

– Modelling estimates very few cases associated with Hajj due to reduced amount of time spent in KSA**

• And also due to the nature of activities of pilgrims

– Worry is visits to health care facilities or camel contact

*Waldrom and Doherty 2015; Kumar et al 2015; Barasheed et al 2015; Aberle et al 2015; Annan et al 2015; Barasheed et al 2014; Benkouitenet al 2014; Gautret et al 2014; Memish et al 2014** Lessler et al 2014

Clues from human epidemiologic studies…

• Numerous seroepidemiologic studies have now been undertaken in several countries including KSA, Qatar, Jordan, Egypt, UAE

– Significantly higher seroprevalence in populations with close, regular and direct contact with dromedary camels

– Only one large population based serosurvey (samples from 2012-2013)*

• 0.2% of general population found to be seropositive

• Significance?

– Likely missing mild cases

– Likely these sub-clinical infections play a (silent) role in transmission in the community

*Müller et al Lancet ID 2015

How are humans infected with MERS-CoVfrom contact with dromedary camels?

Unknown 2:

Photo credit: EPA

Photo credit: Green Prophet News

Some answers from epidemiologic studies (1)

• Risk factors for transmission between camels and humans– Case-control study from KSA* 30 primary cases/116 controls matched

on age, sex and neighborhood• found that direct and non-direct contact with dromedary camels are significantly

associated with infection

• Diabetes, heart disease and smoking independently associated with MERS illness

* Alraddadi et al EID 2016

Exposure OR, 95% CI

Univariate

Direct dromedary contact 3.7, 1.4-11.8

Kept dromedaries in or around home 3.3 ,1.04-10.98

milked dromedaries 10.4, 2.5-inf

Visited farm where dromedaries were present 11.6, 2.7-inf

Live in same household as someone who had visited farm with dromedaries or had direct contact with dromedary camel while there

3.95, 1.2-13.75.0, 1.66-16.9

No increased risk for food consumption, unpasteurized animal milk, camel urine ---

Multivariate

Direct dromedary Exposure aOR 7.5, 1.6-35.3

Some answers from epidemiologic studies (2)

• Risk factors for occupationally exposed individuals– Higher seroprevalence among occupationally exposed individuals, but

risk factors for infection not evaluated

– Many more studies have been/are being conducted

• Many studies are not-yet published

• None have addressed this fundamental question

What improvements are required?

• Improvements in case investigations are urgently needed

– All human cases of MERS-CoV need to be thoroughly investigated

– Including

• Immediate notification of health sector to animal sector if human case reports direct or indirect camel exposure

• Joint animal and human investigations for all community acquired cases

• Monitoring and testing of all contacts regardless of symptoms

• Tracing and testing of animals

• Reporting of follow up for both animal and human investigations

• If PCR positive camel identified, animal sector should inform human sector

– Reporting of PCR positive camels to OIE (Doha Declaration)

• Improvements in prospective studies

Unknown 3:

Nosocomial outbreaks continue to occur, and are unnecessary

Peaks in activity are dominated by nosocomial outbreaks

Riyadh/Jeddah 2014

UAE 2014

Riyadh 2015

KOR 2015

Hofuf and other locations KSA 2014

Al Hasa2013Jordan

2012

Why are nosocomial outbreaks happening?

• Lack of awareness, slow isolation of suspected patients

– Over crowding in emergency departments

– Basic IPC not adequate

– Slow triage/isolation

• Recommendations not being implemented

• Cultural differences in health seeking behavior

Republic of Korea 14 Health Care

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Numberofcases

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RepublicofKorea China Death

Source: Korean Ministry of Health/WHO

HAS THE VIRUS CHANGED?

Unknown 4:

Source: http://dj.kbs.co.kr/resources/2015-06-04/

KCDC, Osong PH Res Perspect 2015

H2H transmission in hospitals

• “Super spreading” events in Korea and in KSA

– 83% of cases in Korea linked to 5 cases

– Not super spreaders – combination of events resulting in amplification in transmission between people

– Role of asymptomatic health care workers

• Role of environmental contamination

– Likely playing a role in nosocomial outbreaks

• Surface contamination

• Air samples

– Likely playing a role in community acquired infections

• Occupationally exposed persons

• Owners/household members of owners

Lee and Wong, IJID 2015

Clustering events

• Clusters of cases among household and “household” contacts

– Limited H2H transmission in households*

– Cluster among expat workers in Riyadh October 2015

*Drosten et al NEJM 2014**KSA CCC Weekly Monitor

Prince Mohammed bin AbdulAziz Hospital

Challenges: Addressing community acquired infections

Epidemiologic investigations in animals and humans are/have been conducted. However…

• Not all results have been publically released and these results are critical

– Develop risk communication materials to protect human health

– Develop specific mitigation measures to prevent human infections from camel exposure

– Design specific epidemiologic studies in at risk populations to evaluate risk factors for camel to human transmission

• Cross-sectional/Longitudinal epidemiologic studies of humans, animals and the environment

– In the Arabian Peninsula and across the region

– Include serology and genetic sequencing in outbreak investigations

How can we stop camel-to-human transmission?

• Active surveillance in animals and humans

• Intensive and joint animal/human investigations for every case (public trust)

• Clear guidance for at risk populations

• Coordinated, multi-site, inter-sectorial human/camel research is needed to better understand transmission patterns

Challenges: Addressing nosocomial outbreaks

• More nosocomial outbreaks are expected – these can be prevented

• Increasing awareness of MERS, especially in countries with close ties to KSA

– for suspicion of MERS

– For early(ier) isolation of suspected MERS patients

• Improvements in basic infection prevention and control procedures, particularly in emergency departments

• More consistent testing of close contacts, especially health care workers and cleaners

• Training in incident management

• Improvement in communication

– Between both public and private hospitals

– In risk communication to general public, to health care providers and to specific occupational groups

Some answers, more questions…

• What is the extent of human infection?– Are asymptomatic laboratory confirmed cases acting as carriers and playing a

significant role in transmission in nosocomial outbreaks? In the community?

– Why 2012 and why so many cases reported from KSA?

• How are humans infected with MERS?– Clues but no definitive answers

– What is the role of environmental contamination?

• How do we stop camel to human transmission?– Is a camel vaccine the answer?

– Can dromedary camels with neutralizing antibodies be re-infected and infectious?

• Why are we still seeing significant nosocomial outbreaks when basic IPC measures can prevent H2H transmission?– Is the virus changing?

Thank you

Special thanks to the WHO MERS-CoV Task Force in HQ/EMRO/WPRO, especially Peter Ben Embarek, Outbreak, Dalia Samhouri, Mamun Malik, Sylvie

Briand, Keiji Fukuda, Ailan Li, CK Lee and many many others

KSA Ministry of Health: Dr Abdul Aziz Bin Saeed, Dr Abdullah Assiri, Hassan Elbushra, FETP Residents