The MERS Coronavirus (MERS Co-V) emerged in 2012 and continues to cause illness and death more than 2 years later. It has been compared to SARS, which caused a pandemic more than 10 years ago, and public health response to MERS-CoV has been modeled on the response to SARS.
Australian Infectious diseases epidemiologist Professor Raina MacIntyre from The School of Public Health And Community Medicine at UNSW, analysed the epidemiologic features of MERS-Cov compared to SARS and shows that it is very different to SARS in a new study, published today in Environment Systems and Decisions (http://link.springer.com/article/10.1007/s10669-014-9506-5/fulltext.html). Many of the features are paradoxical and cannot be explained by known principles of epidemiology. For example, despite outbreaks in hospitals, MERS-CoV was present in several mass gatherings such as the Hajj pilgrimage, and did not result in an epidemic. SARS, which was estimated to be more infectious than MERS-CoV, caused a classic epidemic of over 8000 cases globally and was eliminated from the human population within 8 months. MERS-CoV on the other hand, estimated to be less infectious, has persisted for more than 3 times the duration of SARS. Further, SARS causes satellite epidemics in countries to which it spread, whereas MERS-CoV has remained mainly in the Middle East, without sparking epidemics in other countries where cases have occurred.
In SARS, outbreaks in hospitals were caused by a single strain, but with MERS-CoV, more than one strain of the virus has been identified in some outbreaks. This means that people hospitalized with MERS-CoV or who developed the infection in hospital were exposed to several different viruses at around the same time. Where did these viruses come from? What was the source of infection to humans?
“It is a mystery why this virus, which has low apparent infectiousness has persisted for so long when a consistent source of infections has not been identified.” says MacIntyre. “Infections cannot materialize from thin air. Human beings are being infected from a source, either other humans or a non-human source. A non-human source could be an animal source or deliberate release.”
There is evidence for camels as a source, with a few cases having contact with camels, but many human cases have no known contact with camels or other animals. “The finding of the virus in camels,” says MacIntyre, “does not exclude bioterrorism as a cause. A virus that has a trophism for particular animals, when present in an environment, will tend to infect those animals. It’s a case of which came first, the chicken or the egg.”
The other postulated explanation for the paradoxes of MERS-CoV is that there are many mild or asymptomatic cases which have gone undetected. However, attempts to look for such cases has not turned up high numbers of mild or asymptomatic cases. Whether this is the explanation will become clearer as better screening methods are developed.
Professor MacIntyre fitted the observed features of MERS-CoV to an epidemic pattern and two sporadic patterns – an animal source or deliberate release. The pattern was much more consistent with a sporadic source, with slightly more weight to deliberate release than an animal source, although both are possible.
“It could be either explanation. In the case of bioterrorism, if it is not considered at all, it can never be detected, unless it involves an eradicated pathogen such as smallpox” says MacIntyre. “In public health we are generally not good at interpreting aberrant patterns. A good example is the Rajneesh salmonella attack in 1984 in the US – public health authorities did not consider the possibility of bioterrorism, despite a local politician arguing the case that it might be bioterrorism, and despite the facts not fitting with ordinary food poisoning. If Rajneesh had not confessed later, the attack would have never been recognised, and even when he did confess, he wasn’t believed. This case illustrates normal human tendency to force available facts into common, confortable explanations, rather than to view the facts objectively.”
“The patterns of MERS-CoV are unusual, and whilst an animal reservoir or undetected mild human cases as the source of ongoing human infections are both possible, the possibility of bioterrorism should also be considered, because the data fit this explanation. In the case of deliberate release, simulating nature would be difficult with a sporadic infection, and this may explain the observed discrepancies in the epidemiology.”
“Whatever the source of persistent MERS-CoV infections, using a framework based on SARS to tackle this infection is a mistake, because it is very different to SARS.”
Full paper: http://link.springer.com/article/10.1007/s10669-014-9506-5/fulltext.html
See commentary on Prof MacIntyre’s Infectious Diseases FB page: https://www.facebook.com/ProfRainaMacIntyre?focus_composer=true&ref_type=bookmark
See Conversation comment: https://theconversation.com/mers-coronavirus-animal-source-or-deliberate-release-29690#comment_431898
Raina MacIntyre’s commentary and responses to the paper
The paper has generated heated debate and strong criticisms. A summary of my response to the criticisms/FAQs is here:
1. “There are no new data or science in the paper”:
Epidemiology is a recognised science, and I have used principles of epidemiology and pattern recognition in my paper, something quite simple, but important. Science does not need to be complex to be good. Science can also be very simple and can serve an important purpose. Epidemiology as a science can be as simple or complex as needed, and is not respected as it should be, despite the legacy of John Snow. It is also surprisingly poorly used in public health responses to outbreaks. My academic background in epidemiology, and my field outbreak investigation experience where I have analysed patterns in epidemics and outbreaks, led me to the conclusion that something seemed aberrant about the epidemiological picture of MERS-CoV. This is why I wrote the paper, which is about pattern recognition using epidemiologic principles.
Publicly available data should be analysed and interpreted freely by anyone who chooses to do so, and the more analysis there is, the better we are for it, especially when there are discrepancies and lack of full understanding around a newly emerged infection.
2. “There is no scientific evidence of bioterrorism”:
My paper is not about proving BT - it is about interpretation of the existing public data and explanations for the discrepancies using principles of epidemiology. If a building collapses, even a five-year old can tell if the cause is a bomb or an earthquake. If an epidemic occurs, even the best qualified experts have difficulty determining the cause, as starkly illustrated by the Rajneesh salmonella BT case http://www.foodsafetynews.com/2009/10/for-the-first-12/ . Not only did public health experts fail to recognise it (when the facts supported it), but they came up with an explanation that flew in the face of the data, and they refuted a politician who raised the possibility.
So how do you tell? In terms of the role of public health experts, I think pattern analysis and pattern recognition using epidemiology can help identify aberrant patterns, which can act as a flag for at least raising the question of BT. BT has occurred throughout history, so if an epidemiologic pattern is aberrant, it should be considered. If this flag is raised, the required evidence relies on other experts in other fields.
The evidence required to prove BT is not the kind that any medical or public health researcher could come up with. What evidence is required to "prove" BT? How does isolation of a virus in a lab prove or disprove BT? How does epidemiologic analysis prove or disprove it? It cannnot. We rely on the law enforcement, intelligence and military communities to get the kind of evidence required, and health experts have a fairly poor track record throughout history in having any role at all in identifying BT when it has occurred. Take the Rajneesh Salmonella case, for instance as an example http://www.foodsafetynews.com/2009/10/for-the-first-12/ . In the end the evidence came from a FBI raid on the Rajneesh laboratories.
3. How could BT be an explanation if the virus or a related virus has been in camels for a long time?
My paper is about the human epidemiology, and about explanations for the emergence and persistence of this infection. If the BT scenario is the explanation, it is conceivable that a naturally occurring camel virus has been used and/or modified. We live in an age where genetic engineering of viruses and public availability of methods to do so is a reality (see http://www.cambridgeworkinggroup.org). The first synthetic virus was created in 2002, and synthetic genomics is an unregulated field. Further, genetic engineering of viruses and bacteria is not new, and has been documented 40 years ago in the Soviet Bioweapons Program. (Alibek, K. and S. Handelman. Biohazard: The Chilling True Story of the Largest Covert Biological Weapons Program in the World - Told from Inside by the Man Who Ran it. 1999. Delta (2000) ISBN 0-385-33496-6). So it certainly is a conceivable scenario.
4. Why does the presence of multiple strains support possible BT?
Multiple strains can occur naturally, but this is a newly emerged disease in humans, and the presence of multiple strains in what appears to be a single outbreak with a classic epidemic curve (such as some of the hospital outbreaks) is unusual. We know that predicting the exact genes which cause transmissibility is difficult, and so simulating nature and creating a suitably infectious pathogen of would be difficult for a new infection in humans. So hypothetically, someone planning BT may engineer multiple different strains and release them all in the hope that one will "take off" and cause an epidemic.
5. Is it irresponsible or fuel for conspiracy theorists to raise this possibility?
I think it is irresponsible not to consider it, if it is a possibility. The paper is written primarily for people from the law enforcement / security field / military, as stated in the paper. They think very differently from health scientists, and I feel there is not enough engagement between disciplines in the field of biosecurity. We are all stakeholders in biosecurity, and it should not be the exclusive domain of any one discipline, or of one country (for example decisions made about publishing dual-use research in one country can affect the whole world). Nor does the right to ask questions or to examine publicly available data belong exclusively to anyone. I don’t feel it is wrong to have new ideas or raise new questions. Even if the probability of this being the cause is low, I feel that if there is a possibility (and the data are consistent with this possibility), we have an ethical and moral duty to investigate it.
These are the questions and issues which may explain why my "thinking the unthinkable" and saying it, using a reasoned approach in a peer-reviewed paper has created such a strong reaction. Also see Lauren Gardner's paper using a scenario-based analysis of MERS and the Hajj. http://onlinelibrary.wiley.com/doi/10.1111/risa.12253/abstract
Lauren found the probability of no epidemic arising from 4 mass gatherings over 2 consecutive years is extremely low under currently accepted assumptions about MERS CoV. This suggests to me the accepted assumptions are incorrect, which again points to there being merit in considering the possibility of BT - which is all I raise in my paper. Finally, I have raised it as another explanation for a disease that remains puzzling, but have not dismissed the other prevalent explanations.