Tuesday, 20 October 2015

If you are often in contact with camels are you more likely to acquire MERS-CoV? [spoiler: yep]

This dromedary camel (DC)/Middle East respiratory syndrome (MERS) themed post is a quick review of a paper from 2015 by Reusken and a team of absolute champions in this space. 

It, as many have been, was published in the Emerging Infectious Disease journal, listed in its August issue (but online earlier) and entitled, Occupational Exposure to Dromedaries and Risk for MERS-CoV Infection, Qatar, 2013–2014.[1]

The study examined 498 sera from humans in Qatar split into different exposures types. Included were European (the Netherlands and Germany) human sera for use as controls - collected from a part of the world where there was not expected to have been any MERS-coronavirus (CoV) exposure and so no antibodies were expect to be present; a test for the tests.

As an aside, we've seen some great informative MERS-CoV/camel studies come out of Qatar. I love watching good collaborations pay dividends.

The 498 sera breakdown as follows:
  • 294 from those with daily DC exposure
    • Cohort A: 109 camel (A1; n=5) and sheep (A2; n=104) slaughterers
    • Cohort B: 8 central animal market (CAM) workers
    • Cohort C: 22 healthy males living & working at Al Shahaniya barn complex adjacent to DC race track
    • Cohort D: 155 healthy males living & working at DC farm
  • 204 from those without camel contact
    • Cohort E: 56 samples from construction workers
    • Cohort F: 10 people living in a complex with 200 sheep barns
    • Cohort G: 138 specificity testing samples (66 from the Netherlands and Germany who had recent CoV infection (G1) and 72 from the Netherlands obtained for Bordetella pertussis infection testing (G2)
The antibody testing regimen relied on a multi-tier approach (the best ones do, until we're sure that any single assay can cope with all the variables):
  • Tier 1: IgG antibodies were sought using the MERS-CoV, severe acute respiratory syndrome (SARS)-CoV, human CoV (HCoV)-OC43 spike domain S1 antigen protein-microarray method used previously by this group [2]
    • 20/294 samples (6.8%) reacted (had IgG antibody in them) - none were from controls sera or from those without DC contact
    • 4/22 Cohort C, 8/155 Cohort D, 3/104 Cohort A2 and 4/5 Cohort A1 samples were reactive
    • All samples from A1, A2, B, C, D, E, F and G1 showed responses to HCoV-OC43 S1
    • None of 498 sera reacted to SARS-CoV S1
  • Tier 2: A 90% plaque reduction neutralization test (PRNT90 [4]) was used to show whether antibodies in samples could specifically stop MERS-CoV from infecting cells after sera and virus were co-incubated ahead of infection of a cell line
    • the 20 IgG reactive samples from Cohort A to D were tested and 10 were able to neutralize infection
    • 34/35 samples from those with camel contact (Cohorts A1, B and C) that were IgG non-reactive, also had no neutralizing antibody
  • "Tier 3": Use of a whole MERS-CoV immunofluorescence assay (IFA). However, the results from testing 8 reactive samples (5 of which were positive by IFA) were not included
This paper has a nice central finding which goes something like: if you don't have contact with camels, you don't get infected by MERS-CoV. If you do regularly have contact with camels - you are much more likely to get infected as determined by you having developed antibodies to that virus; you were infected but you fought off the infection. A similar finding came out of the larger serosurvey from the Kingdom of Saudi Arabia.[3] 

I do wonder about the reactive sheep slaughterers though (Cohort A2) - where did those infections come from?  

The authors also addressed why other serologic studies of humans with occupational exposures have not found reactive sera-those studies hardly ever documented infected camels at the workplaces and there may not have been any (for some significant period of time presumably). More infected camels may be associated with more human infections. No surprise. The authors had found, outside this publication, that 60% of camels at the CAM and slaughterhouse were shedding MERS-CoV. This discrepancy has been a question of mine for a long while - and I like this answer.

Interestingly, the participants with antibodies don't recall being seriously sick. So you may get infected and just think you have the flu, or a cold, or nothing at all. This result may further confuse camel-deniers who do not have any background in the wide spectrum of outcomes one can expect after infection by any virus. Nonetheless, such apparently unnoticeable infections add more weight to the story that the current proportion of fatal cases is an exaggeration. So we learned yesterday that MERS (the disease) is rare, that camel contact makes up only a proportion of the likely sources of infection and now we see that you may not even get sick if you do get infected. A few things to digest there.

Also very interesting to me is that the neutralizing antibody titres were lower than had been found elsewhere. The authors suggest this may be due to these infections producing only mild disease. Without a prospective study though, it's very hard to be sure about the true disease severity - recall bias can be a pest. This is an area that needs a more focussed study; do our antibody tools detect mild and asymptomatic cases as reliably as severe MERS cases, for how long and in all cases of infection?

Its feels like its getting pretty hard to mount any realistic case for why we should ignore the role of camels in infecting us with MERS-CoV - even if they do so rarely, and perhaps often without serious complications.

References...
  1. http://wwwnc.cdc.gov/eid/article/21/8/15-0481_article
  2. http://virologydownunder.blogspot.com.au/2015/10/kenyan-camel-coronaviruses.html
  3. http://www.thelancet.com/journals/laninf/article/PIIS1473-3099(15)70090-3/abstract
  4. http://www.thelancet.com/journals/laninf/article/PIIS1473-3099(13)70164-6/abstract