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4 years on, what do we know?
Ian M. Mackay, PhD
Public and Environmental Health – Virology
Forensic & Scientific Services | Health Support Queensland
Department of Health
& Associate Professor, The University of Queensland
Ian.Mackay@health.qld.gov.au
Opinions expressed here are my own; references available upon request
Middle East respiratory
syndrome (MERS)
2PEH FORUM 29SEPT2016
Middle East respiratory syndrome coronavirus
(MERS-CoV)
3
Kingdom of Saudi Arabia (KSA) is the hot zone
•1st
report of novel CoV– 20th
Sept 2012
•Most cases are from human-to-human transmission
• respiratory disease caused by a respiratory virus
• weak & sporadic transmission between humans
• acquired mostly from humans in healthcare settings
•Seroprevalence: 0.15%
• 2013, 15 of 10,009 adults, KSA
• highest seroprevalence among shepherds and slaughterhouse
workers
PEH FORUM 29SEPT2016
The hot zone is hot & subtropical
4PEH FORUM 29SEPT2016
Hajj: “The massest of Mass gatherings”
-Helen Branswell
5PEH FORUM 29SEPT2016
The MERS coronavirus (MERS-CoV)
•Enveloped, 30,000nt (+) RNA virus
•4 structural ( ), 16 NS proteins; recombination
•Little sign of adapting to humans so far
•Single serotype
•Uses dipeptidyl peptidase 4 (DPP4; LRT>URT) for entry
6PEH FORUM 29SEPT2016
Hu et al. Virol J .2015 12:221
Ancestors of MERS-CoV
•Bats
• focus of first papers
• many recent CoVs discovered
• likely ancestor found
•Conspecific virus
• Neoromicia (Pipistrellus)
capensis
• South Africa
• “NeoCoV”
7PEH FORUM 29SEPT2016
8PEH FORUM 29SEPT2016
MERS-CoV in bats
•1 rtPCR amplicon
• 1 sample
• 1 bat
• 1 species (Taphozous perforatus)
• 1,003 samples Oct 2012 / April 2013
• not convincing
9PEH FORUM 29SEPT2016
10
Why camels?
•Important animals – much contact
• Arabian peninsula
•Mild camel disease – common cold
• 1st
MERS case did own camels
• juvenile camels more often virus positive
• high level of virus in camel secretions
• Camel herds can be 100% seropositive
• Camel-to-human infection reported
•No other animal found to host virus
• alpaca with antibody
PEH FORUM 29SEPT2016
11PEH FORUM 29SEPT2016
Camel virus > human spillover
•Same virus in camels & humans
•225 genomes
• 3 genetic groupings
•Camel & human variants
• interspersed
• 96.5-100% nt identity
12PEH FORUM 29SEPT2016
MERS-CoV: A distinct virus
13PEH FORUM 29SEPT2016
“Contact?”
Example of rare contact
14PEH FORUM 29SEPT2016
More likely forms of contact
15PEH FORUM 29SEPT2016
Persistence
•MERS-CoV is stable on surfaces
• more stable than influenza A(H1N1) virus in aerosol (10min) &
on hard surfaces
•MERS-CoV RNA can shed for >1 month
• detected from a HCW for 42 days
16PEH FORUM 29SEPT2016
The disease, MERS
•Incubation period 2-16 days (median 4/5 days)
•Comorbidity (e.g. 87%) & cough (e.g. 100%) common
• asymptomatic
• acute URT illness incl. fever, headache, myalgia
• progressive pneumonitis, respiratory failure, septic shock,
multi-organ failure
•20% -74% (ICU) mortality (median: 12 days onset>death)
• SARS-10%
17PEH FORUM 29SEPT2016
Treatment
•No antivirals available
•Passive immunotherapy (antibody) - clinical effect?
• infrequent donors (2%)
• antibody titres low/short-lived in convalescent human sera
•Vaccines
• a range in the pipeline for humans and animals
•Supportive care
18PEH FORUM 29SEPT2016
19PEH FORUM 29SEPT2016
MERS in humans is about humans with MERS
?
20
MERS: cases driven
by habits and errors?
PEH FORUM 29SEPT2016
South Korea outbreak, May-Dec 2015
•186 cases, 38 fatalities (20%), 4 waves of infection
•Biggest outbreak outside KSA
• >16,000 people quarantined
•No sustained h2h transmission
• no community outbreaks
•1/186 case travelled to China
•7.4 day incubation period (6.2 > 7.7 > 7.9 by generation)
21PEH FORUM 29SEPT2016
South Korea outbreak, May-Dec 2015
•1 patient responsible for 81 cases
• visited 4 hospitals
• coughed in the open
• walked through ER to public toilet
•Receptor binding domain mutant in 13/14 variants
• reduced receptor affinity
• not every virus mutates according to a Hollywood script
22PEH FORUM 29SEPT2016
South Korea outbreak, May-Dec 2015
•Lower proportion fatal
•20% compared to 41% in KSA
• due to the mutation?
• lower % underlying comorbidities in general community
23PEH FORUM 29SEPT2016
South Korea outbreak washup
•Quarantine was initially limited
• casual contacts needed to be included as well as close contacts
•4 beds/room – cases initially not isolated
• overcrowding
•Family members were responsible for some hospital care
• prolonged, close contact
•Patients easily moved between hospitals
• hospitals didn’t share past disease history on patients
24PEH FORUM 29SEPT2016
South Korea outbreak, May-Dec 2015
25PEH FORUM 29SEPT2016
1-Choi. Yonsei Med J. 2015 56(5):1174-76
26PEH FORUM 29SEPT2016
Issues to address large healthcare
outbreaks of MERS
•Identify symptomatic patients early; test & re-test
•Strong contact tracing, monitoring and quarantine
•Strong infection, prevention and control measures
• PPE – selection, use, donning/doffing, disposal
• distance between beds
• be aware of aerosol generating procedures
• cleaning & disinfection
• treat / manage patients in isolation
•Communicate with public to build/maintain trust
27PEH FORUM 29SEPT2016
28
Cases are rare but travel is not
•Control MERS in the hotzone, avoid global spread
PEH FORUM 29SEPT2016
Stop hospital outbreaks, reduce MERS cases
•Humans create circumstances for super-spreading events
29PEH FORUM 29SEPT2016
30PEH FORUM 29SEPT2016
Thankyou

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PEH FORUM_29SEPT2016

  • 1. 4 years on, what do we know? Ian M. Mackay, PhD Public and Environmental Health – Virology Forensic & Scientific Services | Health Support Queensland Department of Health & Associate Professor, The University of Queensland Ian.Mackay@health.qld.gov.au Opinions expressed here are my own; references available upon request Middle East respiratory syndrome (MERS)
  • 2. 2PEH FORUM 29SEPT2016 Middle East respiratory syndrome coronavirus (MERS-CoV)
  • 3. 3 Kingdom of Saudi Arabia (KSA) is the hot zone •1st report of novel CoV– 20th Sept 2012 •Most cases are from human-to-human transmission • respiratory disease caused by a respiratory virus • weak & sporadic transmission between humans • acquired mostly from humans in healthcare settings •Seroprevalence: 0.15% • 2013, 15 of 10,009 adults, KSA • highest seroprevalence among shepherds and slaughterhouse workers PEH FORUM 29SEPT2016
  • 4. The hot zone is hot & subtropical 4PEH FORUM 29SEPT2016
  • 5. Hajj: “The massest of Mass gatherings” -Helen Branswell 5PEH FORUM 29SEPT2016
  • 6. The MERS coronavirus (MERS-CoV) •Enveloped, 30,000nt (+) RNA virus •4 structural ( ), 16 NS proteins; recombination •Little sign of adapting to humans so far •Single serotype •Uses dipeptidyl peptidase 4 (DPP4; LRT>URT) for entry 6PEH FORUM 29SEPT2016
  • 7. Hu et al. Virol J .2015 12:221 Ancestors of MERS-CoV •Bats • focus of first papers • many recent CoVs discovered • likely ancestor found •Conspecific virus • Neoromicia (Pipistrellus) capensis • South Africa • “NeoCoV” 7PEH FORUM 29SEPT2016
  • 8. 8PEH FORUM 29SEPT2016 MERS-CoV in bats •1 rtPCR amplicon • 1 sample • 1 bat • 1 species (Taphozous perforatus) • 1,003 samples Oct 2012 / April 2013 • not convincing
  • 10. 10 Why camels? •Important animals – much contact • Arabian peninsula •Mild camel disease – common cold • 1st MERS case did own camels • juvenile camels more often virus positive • high level of virus in camel secretions • Camel herds can be 100% seropositive • Camel-to-human infection reported •No other animal found to host virus • alpaca with antibody PEH FORUM 29SEPT2016
  • 11. 11PEH FORUM 29SEPT2016 Camel virus > human spillover •Same virus in camels & humans •225 genomes • 3 genetic groupings •Camel & human variants • interspersed • 96.5-100% nt identity
  • 14. Example of rare contact 14PEH FORUM 29SEPT2016
  • 15. More likely forms of contact 15PEH FORUM 29SEPT2016
  • 16. Persistence •MERS-CoV is stable on surfaces • more stable than influenza A(H1N1) virus in aerosol (10min) & on hard surfaces •MERS-CoV RNA can shed for >1 month • detected from a HCW for 42 days 16PEH FORUM 29SEPT2016
  • 17. The disease, MERS •Incubation period 2-16 days (median 4/5 days) •Comorbidity (e.g. 87%) & cough (e.g. 100%) common • asymptomatic • acute URT illness incl. fever, headache, myalgia • progressive pneumonitis, respiratory failure, septic shock, multi-organ failure •20% -74% (ICU) mortality (median: 12 days onset>death) • SARS-10% 17PEH FORUM 29SEPT2016
  • 18. Treatment •No antivirals available •Passive immunotherapy (antibody) - clinical effect? • infrequent donors (2%) • antibody titres low/short-lived in convalescent human sera •Vaccines • a range in the pipeline for humans and animals •Supportive care 18PEH FORUM 29SEPT2016
  • 19. 19PEH FORUM 29SEPT2016 MERS in humans is about humans with MERS ?
  • 20. 20 MERS: cases driven by habits and errors? PEH FORUM 29SEPT2016
  • 21. South Korea outbreak, May-Dec 2015 •186 cases, 38 fatalities (20%), 4 waves of infection •Biggest outbreak outside KSA • >16,000 people quarantined •No sustained h2h transmission • no community outbreaks •1/186 case travelled to China •7.4 day incubation period (6.2 > 7.7 > 7.9 by generation) 21PEH FORUM 29SEPT2016
  • 22. South Korea outbreak, May-Dec 2015 •1 patient responsible for 81 cases • visited 4 hospitals • coughed in the open • walked through ER to public toilet •Receptor binding domain mutant in 13/14 variants • reduced receptor affinity • not every virus mutates according to a Hollywood script 22PEH FORUM 29SEPT2016
  • 23. South Korea outbreak, May-Dec 2015 •Lower proportion fatal •20% compared to 41% in KSA • due to the mutation? • lower % underlying comorbidities in general community 23PEH FORUM 29SEPT2016
  • 24. South Korea outbreak washup •Quarantine was initially limited • casual contacts needed to be included as well as close contacts •4 beds/room – cases initially not isolated • overcrowding •Family members were responsible for some hospital care • prolonged, close contact •Patients easily moved between hospitals • hospitals didn’t share past disease history on patients 24PEH FORUM 29SEPT2016
  • 25. South Korea outbreak, May-Dec 2015 25PEH FORUM 29SEPT2016 1-Choi. Yonsei Med J. 2015 56(5):1174-76
  • 27. Issues to address large healthcare outbreaks of MERS •Identify symptomatic patients early; test & re-test •Strong contact tracing, monitoring and quarantine •Strong infection, prevention and control measures • PPE – selection, use, donning/doffing, disposal • distance between beds • be aware of aerosol generating procedures • cleaning & disinfection • treat / manage patients in isolation •Communicate with public to build/maintain trust 27PEH FORUM 29SEPT2016
  • 28. 28 Cases are rare but travel is not •Control MERS in the hotzone, avoid global spread PEH FORUM 29SEPT2016
  • 29. Stop hospital outbreaks, reduce MERS cases •Humans create circumstances for super-spreading events 29PEH FORUM 29SEPT2016