Copyright: Marcel A. Müller Dr. Marcel A. Müller Institute of Virology University of Bonn Medical Center Bonn, Germany [email protected]www.virology-bonn.de January 20th, 2016 CONSISE Meeting Paris PCR vs. Serology – example MERS How to interpret results in seroepidemiologic studies
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PCR vs. Serology example MERS How to interpret … · Jan Felix Drexler Souhaib Aldabbagh Sebastian Brünink Acknowledgments Funding: BMBF (SARS), DFG Africa, DFG SPP1596, EU grants
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Calves, <1 yr 92/108 (85.2) 24/68 (35.3) 6/44 (13.6)
Young camels < 1 year virus-positive!
SE
RO
LO
GY
+P
CR
Copyright: Marcel A. Müller
Long-term and widespread circulation of
MERS-CoV in dromedaries
1983/84 Sudan/Somalia
Müller et al. EID 2014
1992-96Saudi Arabia
Alagaili et al.mBio 2014
2009/10Saudi Arabia
Alagaili et al.mBio 2014
1997Egypt
Müller et al.EID 2014
2003UAE
Meyer et al. EID 2014
2013UAE/Oman/
Egypt/ Jordan
Meyer et al. EID 2014Reusken TLID 2013Chu et al. EID 2013Reusken et al.Euro Surv 2013Perera et al.Euro Surv 2013
1992Kenya
Corman et al EID 2014
2010/11Ethiopia/ Nigeria
Reusken et al.EID 2014
2009Tunisia
Reusken et al.EID 2014
Red=Africa
Black=Arabian Peninsula
SE
RO
LO
GY
+P
CR
Copyright: Marcel A. Müller
MERS-CoV originates from Africa
Nigeria
Egypt
Arabian
Peninsula
Korea
First human isolate
Egypt
PC
R
Copyright: Marcel A. Müller
2. Outbreak: Jeddah April 2014
PCR diagnostic laboratory artifact? NO CONTAMINATION
Increase of zoonotic transmission?
Mutant Virus?
Drosten et al. 2014, CID
2014
PC
R
Copyright: Marcel A. Müller
Monophyly of Jeddah outbreak viruses
Jed
dah
Single introduction of virus in Jeddah outbreak
7 full-length genomes
Jeddah viruses monophyletic
Drosten et al. 2014, CID
PC
R
Copyright: Marcel A. Müller
Diagnostic laboratory artifact? NO CONTAMINATION
Increase of zoonotic transmission? NO
Mutant Virus?
Drosten et al. 2014, CID
2014
PC
R
Copyright: Marcel A. MüllerDrosten, Muth, Corman, Hussain et al., CID 2014
No hints toward
changes in shedding
from patients
No relevant / unique
changes in spike
ALIGNMENT OF SEQUENCES
PC
R
Copyright: Marcel A. Müller
Nosocomial outbreak in Jeddah
Nosocomial infections starting at
King Fahd Hospital
Drosten et al. 2014, CID
Copyright: Marcel A. Müller
Tested >10,000 serum samples from all 13 provinces
3. Cross-sectional serosurvey in
Saudi Arabia
Müller et al. 2015, Lancet ID
SE
RO
LO
GY
AGE RANGE
Copyright: Marcel A. Müller
Screening 152 (1.5%)
Stage 1 17 (0.2%)
Stage 2 15 (0.2%)
Results cross-sectional study
S1 ELISA
S1 ELISA rIFA full S
S1 ELISA rIFA full S PRNT
Total N=10,009
Müller et al. 2015, Lancet ID
SE
RO
LO
GY
Copyright: Marcel A. Müller
Müller et al. 2015, Lancet ID
-15/10,009 (0.15%) in 6/13
provinces had MERS
antibodies (asymptomatic!)
-up to 23-fold increase in
camel-exposed individuals
Seroprevalence in Saudi Arabia
Copyright: Marcel A. Müller
Saudi-Arabia
26 Index MERS Patients
–
280 Household Contacts
Drosten et al. 2014, NEJM
Case-contact studyS
ER
OL
OG
Y+
PC
R
Copyright: Marcel A. MüllerDrosten, New England Journal of Medicine 2014
26 MERS Patients
RT-PCR
7 positive
280 Contacts
Serology
5 positive
12 transmissions in
26 households, max 1 transmission per
householdR < 0.5
Copyright: Marcel A. Müller
Overview/ Summary
Study PCR Serology
1. Source -Identify virus and putative mutations-Phylogenetic analyses-Monitor acute infection in animals
-Largescale screening of livestock-Retrospective detection-Infection dynamics in livestock
2. Outbreak -Identify virus and mutations-Phylogenetic analyses-Monitor patients and contacts-Quarantine decision making-Prognostic value (e.g. viral load andoutcome of disease)
-Identify asymptomatic cases, contacts (e.g. HCW)-Retrospective control ofquarantine success-Prognostic value (antibody kineticsand outcome of disease)
3. Cross-sectionalserosurvey
Not applicable -Largescale screening of human sera for „background“ seroprevalence-Seasonality
4. Case-contact -Identify acutely infected contacts-Quarantine decision making-R0 value estimates
-Identify unrecognized(asymptomatic) contacts-R0 value estimates
Copyright: Marcel A. Müller
Open questions
R0<1
Young camels
as amplifiers
Hospital
outbreaks„Silent“
transmissions
MERS-CoV a common cold virus for
camels! Why?
Has camel MERS-CoV evolved towards
better transmissibility? Look at diversity of
camel-associated MERS-CoV in Africa, old
respiratory samples needed!
Influence of husbandry, farming?
Seasonality? Parturition differences
between African countries and Arabian
Peninsula!
Are there human cases in Africa? Lack of
testing, predispositions, co-morbidities?
MERS: Why 2012? Only on the Arabian Peninsula?
Copyright: Marcel A. Müller
Intervention?
Hygiene
In hospitals, ER
Avoid contact with (young)
camels
Vaccination
MVA-based vaccine:
Phase 1 clinical trial
planned
Proof of principle
vaccination in camels
showed protection
(Haagmans et al Science
2015)Source: CDC und REUTERS/Faisal Al Nasser
Copyright: Marcel A. Müller
Capacity building/ workshops
First WHO-MERS diagnostic workshop in Dubai in 2015 organized
by WHO-EMRO, University of Bonn, MOH Dubai, CVRL and