Stuff about MERS-CoV that may not have been talked about here and isn't just about humans

Epidemiology of MERS-CoV in humans

Ian M. Mackay, PhDian.mackay@uq.edu.au

Affiliation: Adjunct Associate Professor, University of Queensland

Opinion: my own and not that of any Institution 1

Stuff about MERS and MERS-CoV

that may not yet have been talked about here and isn’t

just about humansIan M. Mackay, PhD

ian.mackay@uq.edu.au

Affiliation: Adjunct Associate Professor, University of Queensland

Opinion: my own and not that of any Institution 2

Briefly..

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o Numberso Animal host – suspects, culprits & how humans may be infectedo Hospitals and circumstance outbreaks in humans o Age, sex, fatalityo MERS as a warning sign for population health

o Publicly available data• World Health Organization• Ministries of Health• FluTrackers

The data I will show you..

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It started by eMail - 20-Sept-2012

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Published Date: 2012-09-20 15:51:26Subject: PRO/EDR> Novel coronavirus - Saudi Arabia: human isolate Archive Number: 20120920.1302733NOVEL CORONAVIRUS - SAUDI ARABIA: HUMAN ISOLATE***********************************************A ProMED-mail posthttp://www.promedmail.orgProMED-mail is a program of theInternational Society for Infectious Diseaseshttp://www.isid.org

Date: Sat 15 Sep 2012From: Ali Mohamed Zaki <azaki53@hotmail.com> [edited]

A new human coronavirus was isolated from a patient with pneumonia by Dr Ali Mohamed Zaki at the Virology Laboratory of Dr Soliman Fakeeh Hospital Jeddah Saudi Arabia.

The virus was isolated from sputum of a male patient aged 60 years old presenting with pneumonia associated with acute renal failure. The virus grows readily on Vero cells and LLC-MK2 cells producing CPE in the form of rounding and syncetia formation.

[The clinical isolate] was initially tested for influenza virus A, influenza virus B, parainfluenza virus, enterovirus and adenovirus, with negative results. Testing with a pancoronavirus RT-PCR yielded a band at a molecular weight appropriate for a coronavirus. The virus RNA was tested also in Dr. Ron Fouchier's laboratory in the Netherlands and was confirmed to be a new member of the beta group of corononaviruses, closely related to bat coronaviruses. Further analysis is being carried out in the Netherlands.

The Virology Laboratory at the Dr Fakeeh Hospital will be happy to collaborate with others in studies of this virus.

--Ali Mohamed ZakiProfessor of MicrobiologyDr Fakeeh hospital Jeddah Saudi Arabia

Numbers summary

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o 21MAR2012 to 10DEC2015o 1,633 laboratory confirmed

cases • cf WHO – 1,621

o ≥584 deaths (36% of cases)• Publicly – 532/482

o 26 countries• 13 with ongoing spread

o Year by year• 2012-16 (incomplete year)• 2013-171 (take-up of testing)• 2014-777• 2015-669

The MERS waves

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The iceberg idea..

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How much MERS-CoV is there?

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o Subclinical shedding reported • 40F HCW RNA(+) for 42 days• Role in transmission?

o 5,065 individuals, 1-Oct-2012 to 31-Sept-2013• 108 RNA POS (2%); 99 adults; 62 male; 70 hospitalized

o Jeddah-2014 outbreak, ~5,000 samples• ~140 RNA POS (~3%)

o Household transmission study• 14 of 280 contacts in 26 households (5%)

o Serosurvey of KSA• 0.15% - 15-23X higher in shepherds & slaughterhouse workers

o 2-3% virus prevalence for other HCoVs in Qld hospital popn

Drosten C et al. N Engl J Med 2014 371:828-835

The MERS-CoV host suspects…

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Coronavirus tree of life

11Chan JFW et al. Clin Microbiol Rev 2015 28(2):465-522

Bats do harbour many CoVs

12Chu DK et al. Eurosurveillance 2015 20(49):Article 3

o But MERS-CoV?

o 1 rtPCR amplicon sequence from 1 sample from 1 bat from 1 species-1,003 samples Oct2012 / April 2013

Human and camel MERS-CoV

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Closely related (>99.7% Clade A and B)

Mackay IM& Arden KE. Virus Res 2015 202:60-88

MERS-CoV diversity reservoir in Africa?

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o Viral RNAo Egypt camels

• Sudan?• Ethiopia?

o Nigeria camels• Northern

Nigeria?• Chad?• Mali?• Liberia?• Niger?• Sudan?

o Africa the site of batcamel transference(s)?

o Academic question?

Chu DK et al. Eurosurveillance 2015 20(49):Article 3

Infection: a rare camel-to-human event

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o Seasonal?

Transmission is sporadic

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Direct contact-includes many things

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How might a camel infect a human?

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Direct animal exposure

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‘…in the 14-days before illness onset was defined asphysical contact with animals or animal products (carcasses, body fluids, secretions, urine, excrement, or raw meat) in any setting (farm, livestock market, slaughterhouse, racetrack, stable, or other animal-related venue) or engaging in certain animal-related activities (feeding animals, cleaning housing, slaughtering, assisting with birth, milking, kissing or hugging or other related tasks)”

Risk factors for primary Middle East respiratory syndrome coronavirus illness in humans, Saudi Arabia, 2014Alraddadi et al. Emerg. Inf. Dis. 22(1) January 2016

Camels and public data

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Camel, goat or unspecified animal contacts noted among MERS-CoV cases by likely site of acquisition.

Total numbers

UAE KSA Qatar Oman Kuwait YemenUAE KSA Qatar Oman Kuwait Yemen

0%

25%

50%

75%

100%

Camel, goat or unspecificed animal contacts noted among MERS-CoV cases

by likely site of acquisition.Proportion of cases at that site

7.4%

“Primary” cases and public data

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KSA MOH CCC: www.moh.gov.sa/en/CCC/PressReleases/Pages/default.htm

PrimaryCases in persons without known exposure to other MERS-CoV cases or recent (14d) exposure to healthcare settings

Human sampling

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o Initially a respiratory diseaseo Receptor is rare (but present)

in upper airwayso URT most common sampling

site

o Humans create the conditions• Super-spreading circumstances

o Testing to learn moreo Awareness to prevent spread

• Education and information• Societal change• Infection prevention and control

Outbreaks enabled by circumstance

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What transmission role for mild disease?

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Hospitals central to cases: 2012-2015

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Healthcare workers (HCWs) and MERS

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MERS cases by site of acquired infection

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80%

11%

MERS in countries with positive camels?

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?KENYA

?ETHIOPIA

?NIGERIA

?EGYPT

?TUNISIA

MERS-CoV but no MERS in Africa..?

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MERS and gatherings..

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MERS and season..

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MERS and region..

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o Antibody levels also higher in central regions

Ar Riyad province

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2012 2013 2014 2015

o Frequency increasing?

Makkah province

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2012 2013 2014 2015

MERS and the older male

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South Korea: an external outbreak

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o Median age, Kingdom of Saudi Arabia: 48y (death – 48y)

o Median age, South Korea: 55y (death – 47y)

South Korea: an external outbreak

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Fatal MERS cases

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SOUTH KOREA KINGDOM OF SAUDI ARABIA

%ALL DEATHS THAT WERE MALE 67% 70%%ALL DEATHS THAT WERE FEMALE 33% 30%

%INFECTED MALES WHO GO ON TO DIE 22% 35% (1.6X)%INFECTED FEMALES WHO GO ON TO DIE 16% 28% (1.8X)

%MERS ALL CASES THAT DIED 19% 43% (2.3X)

MERS severity and underlying disease

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o Most cases have an underlying condition• Population specific variation?• 96% of 1st 47 cases, 2013• Case study, 2015*• Diabetes*• Chronic lung disease*• Heart disease**significantly more frequent in 2015 case control study; n=30 primary cases

o Asymptomatic cases• Do occur• Younger, healthier, healthcare workers• No study of seroconversion among these• No understanding of role in transmission

o Q: MERS; specific to MERS-CoV or “normal” opportunism for a HCoV in this population?• Time for a better baseline?

Take home points…

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o Camels host MERS-CoVo Camel>>human infection is rare, even with prolonged

contacto MERS is a human diseaseo MERS transmission is mostly a solvable human

problemo MERS in humans in other camel(+) African nations?o Population differences in death rateo Impact of other respiratory viruses in Peninsula

populations?o Are clusters/outbreaks steady?

Thank you

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o University Hospital Bonn• Organizational team

o Central Veterinary Research Laboratory

o World Health Organization–EMROo United Arab Emirates Ministry of Health

o The University of Queenslando Dr. Katherine Arden