MERS coronavirus

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MERS – a bioterrorist plot?

Two publications from Raina MacIntyre of the School of Public Health and Community Medicine, University of New South Wales[i] suggest that bioterrorism or accidental lab release could explain the origin of the MERS coronavirus. Is this a possibility? For me the answer is a very firm NO.

 

In essence the authors use standard epidemiology parameters to assess the pattern of MERS infections to date. The methodology is fine but the dataset used is not. The accepted problem for any modelling is the quality of the data used for the predictions, cynically termed the GIGO problem (garbage in, garbage out), a minor change in which can have a disproportionally big outcome. Think about the numbers that were predicted to have nvCJD (human BSE) or to die in the last influenza pandemic – both hugely overestimated early on in the epidemics. The issue with MERS is the dataset is small and much of it uncertain (the number of cases increased sharply following the change of Saudi health minister in June but these cases were mostly anecdotal as the patients are all dead. The precise details of the cases and technical proof of MERS infection are lacking). It is true that the exact origin and route to man is still unclear but there are no grounds to invoke bioterrorist or accidental release. For bioterrorism the virus clearly doesn’t work well in man so is hardly going to change the course of anything – it is a poorly transmitting virus so why would it be released? And who is it targeted at? Similarly, accidental release would require a local lab working on the virus or a very similar virus – none known, especially in the Middle East. In the latter case the epidemiology would also clearly trace back to the originating lab instead of being all over the place.

Death

 Pieter Bruegel’s “The Triumph of Death” is a favourite accompanying picture for bioterrorism texts. But is it a realistic scenario for the Middle Eastern Respiratory Syndrome coronavirus?   

The latest molecular studies show that the virus is able to infect camel, goat, cow, and sheep cells, which would fit the idea of a zoonotic origin (probably bats) that gets across to domestic livestock, likely as a silent infection that is not reported. Occasionally and via circuitous routes it gets to man where it can lead to severe respiratory distress, especially if the patient is already compromised in some way. The age and male predominance of cases to date fits with typical social roles that would interface with livestock. My own view is that low level contamination of food is also a possibility and the recent finding that the virus can survive for several days in unpasteurised milk shows this is a realistic possibility. Overall however the data are too fragmentary to offer a clear answer.

 

The papers from UNSW do not offer any direct evidence for a deliberate or accidental release of MERS-CoV. With our present state of knowledge you might as well drag up viruses from outer space (nonsense that was wrongly invoked to explain the SARS outbreak). It is none of these things. MERS CoV is a newly recognised and rare zoonotic infection whose pattern of spread will only become clear when more case controlled studies like those recently initiated by the new Saudi health minister have been completed. Science will get to the bottom of MERS, not speculation.

[i]

  1. MacIntyre CR. The discrepant epidemiology of Middle East respiratory syndrome coronavirus (MERS-CoV). Environment Systems and Decisions. Formerly The Environmentalist. 2014 10.1007/s10669-014-9506-5
  2. Gardner LM, MacIntyre CR. Unanswered questions about the Middle East respiratory syndrome coronavirus (MERS-CoV). BMC Res Notes. 2014 Jun 11;7:358. doi: 10.1186/1756-0500-7-358.

 

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What goes around, comes around

The summer lull in virus news (and blogs) is an annual event[1]. Viruses transmit less in warm and dry conditions, being more active in the winter months when the cold and damp conditions coupled with the lower UV levels favour survival. As a result, we can look forward to the regular upturn in cases of respiratory viruses and gastrointestinal viruses (from the excesses of the season) as we run up to Christmas and beyond. A few virus infections did make the headlines in the late summer, chief among them the MERS coronavirus, whose origin is still not clear despite the case for camels as at least an animal of distribution growing stronger[2]. I am not convinced it is the full story as camel farmers, herders and camel riding tourists are not over-represented in those infected. However I am very pleased that MERS CoV did not cause any disruption to the Hajj (as I suggested on Radio Free Europe – [3]) and that the case rate has not increased significantly. My view that this is an occasional zoonotic infection (see my article in Microbiology Today[4]) remains intact.

But what of the coming months?

Influenza in the southern hemisphere this year (considered to be an indicator for what we will get this winter) has again been more serious than previous years[5] with the pandemic H1N1 (originally Mexican flu or swine flu) predominating across the country. Other virus serotypes (H numbers) are also circulating, depending on the state, so exactly what we are in for is unclear. As outlined last year[6], despite predictions of a serious outcome, the reality is often different and whilst an increase in influenza activity is certain in the coming months, the level and extent of infection remains impossible to guess at this time.

Disappointing news recently on two viruses for which vaccine based prophylaxis is available: Human Papillomavirus (HPV) and Polio. In the case of HPV a recent study on vaccine uptake in the UK has revealed that minority populations are less likely to take the vaccine[7]. There is no simple explanation for this, suspicion, culture and apathy all conspire to make these girls (in the UK boys are not vaccinated despite it being a useful thing to do) more at risk of cervical cancer in the future, what a waste. Preventative medicine is just that: it does not seek to best guess who is most likely to get any particular disease, it just assumes that everyone is at risk and acts accordingly. The concept of herd immunity means that everyone benefits as long as the general level of immunity in the population reaches a certain threshold. Both HPV vaccines on the market, Cervarix (from GSK) and Gardasil (from Merck), are recombinant so there is no chance of infection and the mass vaccination campaigns to date show them to be entirely safe: there is no justifiable reason not to take them, only prejudice. Cervarix has recently been approved as a two-dose vaccine, down from the three doses currently recommended. Perhaps that will improve uptake rates somewhat.

The disappointing Polo news is a flare-up of cases in Syria because of the war. The loss of infrastructure has meant that vaccination teams cannot access all the child populations that would normally receive the vaccine. People transiting from the last remaining areas of polio infection through the Middle East has resulting in live virus shedding into the environment so any unprotected child in the area is at risk. The result is a double-whammy of infected children and a setback for the global polio eradication campaign.

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Summer’s here but where are the viruses?

The warmer weather has brought a lull in the number of infections reported in the press. It is a fact that, in the western world, almost all of our seasonal virus infections peak in the winter months. A combination of crowding, lower temperatures, lower levels of UV radiation (which inactivates viruses) and wet conditions or rather non-desiccating conditions, act together to favour virus survival and the cases of infection rise accordingly. Food borne bacterial infections show the opposite trend, peaking with the barbecue and salad season (Figure 1).

summer

Figure 1. Google trends of the seasonal variation in infectious disease – Influenza in red and Salmonella (typical bacterial food poisoning) in blue. The data is for 2012 but is typical of any year except those with unusual events (like the 2009 pandemic).

But what has happened to the infections that were of such concern only a few months ago?  Here is a quick update:

Norwalk like viruses

As predicted in these pages[1] the highly seasonal winter vomiting virus is no longer widely reported despite a very active season aided no doubt by the cold weather which extended to March and April. Isolated outbreaks still occur and cruise ships continue to be plagued by the virus as a result of their isolated and crowded status, a modern day cabin fever, but the general surge of cases is over for the time being. Six months from now will be a different story although you will be forgiven for thinking you have heard it all before.

MERS Coronavirus

The number of cases of the new coronavirus, whose epicentre of infection seems to be the Middle East, has declined. WHO reports a cumulative total of 96 cases and 46 deaths to date[2] but the incidence rate seems to have dropped although this could be, in part, because there were a number of cases in the system that were only confirmed once the causative virus was discovered. The source of the virus remains unknown: an animal reservoir is often suggested and a recent candidate has emerged from epidemiological tracing – the dromedary camel has shown the presence of antibodies to the virus which suggests they have been infected in the past. They obviously feature in the Middle-East but I am not yet convinced they are the source of infection: camel herders seem not to have been infected and surely those that race, milk or slaughter the animals would have received the virus. What about all the tourists who take camel rides and have their picture taken patting their steed, would they not have been obvious potential patients?  We must wait for more data on how the virus gets into camels and the possible ways in which it could be transmitted further. I have suggested that intermittent contaminated food could be a source of infection although, as for other intermediate animals , there is no direct evidence for this. The possible routes of infection are summarised in Figure 2.

transmission

Figure 2. The possible routes to man for the MERS coronavirus. The current data is insufficient to suggest one is more likely than any other despite evidence for the virus circulating in camels.

Quite a lot of coverage has been devoted to the risk to travellers to the forthcoming Hajj. With such low numbers of infections and no real idea where the virus is, my stated view is that no special measures beyond those associated with large gatherings need to be taken.[3] I have an opinion piece on the virus in the August issue of the SGM’s Microbiology Today – take a look.[4]

Influenza H7N9

The incidence of H7N9 in China peaked in April and has since declined although sporadic cases continue to be reported. More than 130 people have been infected and about 1/3rd of them have died. This is the biggest breakthrough of H7 avian influenza to date, certainly the most serious and the combination of H7 and N9 is unique and may be part of the reason for the success of the virus in diverse hosts. To rehearse some well-known background, influenza A viruses are naturally distributed among avians and intermixing occurs all the time as the virus jostles within each host to make more of itself in the face of an immune response which tries to restrict it. Some of these combinations result in viruses that by chance are adapted to transmit and grow in mammalian hosts, typically pigs and man. The presence of such a virus in migratory birds is not really an issue as the chance of an encounter with man is very limited but if the virus gets into domestic poultry the opportunity for the virus to transmit to man goes up substantially and local infections, usually clustered, begin to be seen. While causing infections in people there is a finite chance that the virus will adapt to spread among people more easily and so trigger a pandemic although these events are rare (1957, 1968 and 2009 being the last true pandemics). In this case the H7N9 virus seems to have arisen by a three way mix of viruses in or around the Yangtze river delta during 2012 from where the virus moved into local domestic birds. The authorities’ action of closing live bird markets is presumed to have led to the sudden fall off in the number of cases but the virus itself is still around, just the opportunity to transmit to man has been made much less likely. As with the H5N1 virus, sporadic infections are likely to continue but as the virus has not shown an ability to transmit between people it is not thought currently to represent a pandemic risk.[5]