Tuesday 27 May 2014

Camels and MERS: links to peer-reviewed scientific literature...[UPDATE #2]

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Camels at the centre, aerosol all around...
I thought this might be a useful page for anyone who would like to know just how much data has been generated that supports a link between camels and MERS-CoV, and studies that have shown near identical viral genomes from camels, and the humans in contact with them. 

Its also worth nothing only 1 ~180nt PCR fragment from 1 bat in 1 study has had a MERS-CoV sequence detected in it and yet they are still considered the most likely ancestor of the MERS-CoV because bats seem to be the ancestral source of many CoVs. 

No studies have found MERS-CoV or infection-blocking (neutralizing) antibodies to MERS-CoV in any non-human or non-dromedary camel animal despite investigation of:

  • horses
  • llamas
  • alpacas
  • bactrian camels
  • guanaco
  • goats
  • sheep
  • water buffalo
  • cows
  • birds
  • pigs
  • chickens
While rats and mice have not been tested in the wild, deliberately inoculated lab mice and Syrian hamsters do not support growth of MERS-CoV and 2 rat cell lines (Chan et al. J Infect Dis. 2013;207:p1743-52) did not support viral transcription or growth. Not the end of the small animal story of course and more testing of small animals is a good thing, but neither has the camel story been completed yet (finding infectious virus in milk, urine and meat and some air sampling and testing from around camels would be nice). However, the camel story does already have some very solid chapters suggesting humans could be coming into sporadic contact with the virus. 

So a few quick thoughts to put camels in context with sporadic infections that are not traceable to contact with a known human case. 

  1. I don't think any scientist has ever suggested every camel is carrying/shedding MERS-CoV all the time. Nothing supports that. 
  2. Most MERS-CoV cases have been from spread between humans and most of those are now linked with hospital-based settings (thanks Jeddah outbreak!). Whether community spread is ongoing is completely unknown until someone tests the community, post-Jeddah outbreak, and not people linked to hospitalized confirmed cases (they only bias the results). 
  3. As we saw in 2nd and 3rd US MERS-CoV detections, 2 face-to-face business meetings, 1 with at least 40-min of face time, and a handshake, was sufficient to pass along MERS-CoV between humans when the index case was not all that ill. 
    • I hope the R0 guys can build this sort of event into their predictive models and 
    • I think this has real and major implications for what "contact" with a camel actually means. I have serious doubts that people who are RT-rtPCR positive and being interviewed and asked about their exposure to camels would think of being near a camel as contact with camels. Is that how they are being asked?
Better understanding the proximity-possibility needs experimental testing but in the meantime it is also very important for those who are asking infected people about their animal exposures and contacts to understand that respiratory viruses don't just spread by physical contact. I am unaware of what is being asked and in how much detail - this may already be well understood. 

If people being asked about past contact with camels are thinking "hey, yeah, I was walking between camel pens for 20 minutes, but no I didn't kiss one or lick its nose or feed it or anything touchy-feely" (I'm 100% certain those would be exactly the words in their heads) - then they may well say "no contact". To my mind, that level of proximity in that example, especially if 1 or 2 of those camels was symptomatic, would be contact.

Anyway, do let me know if I've missed any papers below - or if new references come out.

Camels in the literature...
  1. Reusken CB, Haagmans BL, Muller MA, Gutierrez C, Godeke GJ, Meyer B et al. Middle East respiratory syndrome coronavirus neutralising serum antibodies in dromedary camels: a comparative serological study. Lancet InfectDis 2013 October;13(10):859-66.
  2. Perera RA, Wang P, Gomaa MR, El-Shesheny R, Kandeil A, Bagato O et al. Seroepidemiology for MERS coronavirus using microneutralisation and pseudoparticle virus neutralisation assays reveal a high prevalence of antibody in dromedary camels in Egypt, June 2013. Euro Surveill 2013;18(36):ii.
  3. Hemida MG, Perera RA, Wang P, Alhammadi MA, Siu LY, Li M et al. Middle East Respiratory Syndrome (MERS) coronavirus seroprevalence in domestic livestock in Saudi Arabia, 2010 to 2013. Euro Surveill 2013;18(50):20659.
  4. Reusken CB, Ababneh M, Raj VS, Meyer B, Eljarah A, Abutarbush S et al. Middle East Respiratory Syndrome coronavirus (MERS-CoV) serology in major livestock species in an affected region in Jordan, June to September 2013. EuroSurveill 2013;18(50):20662.
  5. Haagmans BL, Al Dhahiry SH, Reusken CB, Raj VS, Galiano M, Myers R et al. Middle East respiratory syndrome coronavirus in dromedary camels: an outbreak investigation. Lancet Infect Dis 2014 February;14(2):140-5.
  6. Alexandersen S, Kobinger GP, Soule G, Wernery U. Middle East respiratory syndrome coronavirus antibody reactors among camels in Dubai, United Arab Emirates, in 2005. Transbound Emerg Dis 2014 April;61(2):105-8.
  7. Alagaili AN, Briese T, Mishra N, Kapoor V, Sameroff SC, Burbelo PD et al. Middle East respiratory syndrome coronavirus infection in dromedary camels in Saudi Arabia. MBio 2014;5(2):e00884-14.
  8. Meyer B, Muller MA, Corman VM, Reusken CB, Ritz D, Godeke GJ et al. Antibodies against MERS coronavirus in dromedary camels, United Arab Emirates, 2003 and 2013. Emerg Infect Dis 2014 April;20(4):552-9.
  9. Hemida MG, Chu DKW, Poon LLM, Perera RAPM, Alhammadi MA, Ng H-Y et al. MERS Coronavirus in dromedary camel herd, Saudi Arabia. Emerg Inf Dis2014;20(7).
  10. Nowotny N, Kolodziejek J. Middle East respiratory syndrome coronavirus (MERS-CoV) in dromedary camels, Oman, 2013. Euro Surveill2014;19(16).
  11. Raj VS, Farag EABA, Reusken CBEM, Lamers MM, Pas SD, Voermans J et al. Isolation of MERS Coronavirus form a Dromedary Camel, Qatar, 2014. Emerg Inf Dis 2014;20(8).
  12. Corman VM, Jores J, Meyer B, Younan M, Liljander A, Said MY et al. Antibodies against MERS Coronavirus in Dromedary Camels,Kenya, 1992-2013. EmergInf Dis 2014;20(8).
  13. Chu DKW, Poon LLM, Gomaa MR, Shehata MM, Perera RAPM, Zeid DA et al. MERS coronaviruses in dromedary camels, Egypt. Emerg Infect Dis 2014;20(6).
  14. Ziad A. Memish, Matthew Cotten, Benjamin Meyer, Simon J. Watson, Abdullah J. Alsahafi, Abdullah A. Al Rabeeah, Victor Max Corman, Andrea Sieberg, Hatem Q. Makhdoom, Abdullah Assiri, Malaki Al Masri, Souhaib Aldabbagh, Berend-Jan Bosch, Martin Beer, Marcel A. Müller, Paul Kellam, and Christian Drosten. Human Infection with MERS Coronavirus after Exposure to Infected Camels, Saudi Arabia, 2013. Emerg Inf Dis 20(6) (online May 16)
  15. Esam I. Azhar, Ph.D., Sherif A. El-Kafrawy, Ph.D., Suha A. Farraj, M.Sc., Ahmed M. Hassan, M.Sc., Muneera S. Al-Saeed, B.Sc.,Anwar M. Hashem, Ph.D., and Tariq A. Madani, M.D. Evidence for Camel-to-Human Transmission of MERS Coronavirus
  16. NEJM June 4.
    NB. This study is the same human case and camel herd tested in #14. Sampling times differ subtly.

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