Updating the animal "to-do" list...

I have a couple of talks coming up, so I'm making graphics again. And I like to share those. 

This one is an update on some of the creatures that could also be considered suspects in the hunt for sources of MERS-CoV infection of humans.

Of course, camels are the ones we know to be a true risk for infection and there was that 1 bat that was positive for a very small diagnostic PCR product. Cattle contact was also recently listed, with little detail, as a significant risk factor among those acquiring MERS-CoV infection and we also know that cells from camels, horses, alpacas, cattle and goats can be infected and host genome or virus replication of MERS-CoV in the lab, or have the MERS-CoV cellular receptor, DPP4, on their surface.[1,2]

I heard that there will be more bat testing in the future, but we haven't read of any MERS-CoV targeted bat studies since 2013.

So here is the long laundry list of animal testing that needs more work - many of which have been tested in small numbers over limited time periods already - in a graphical form.

Click on image to enlarge.
You can also access this from Figshare.[3]

References...

1. http://www.ncbi.nlm.nih.gov/pubmed/25656066
2. http://wwwnc.cdc.gov/eid/article/22/1/15-1340_article
3. http://figshare.com/articles/Creatures_of_interest_to_how_humans_acquire_a_MERS_CoV_infection/1609604

Monkey magic: Vero cells make more MERS-CoV RNA than any other animal's...

Apart from camel, goat, bat and human cells which draw the eye in studies on the source of MERS-CoV, did anyone notice the Vero cells? 

These cells are derived in the dim dark ages from African green monkey kidney (Cercopithecus aethiops). After infection, these monkey cells were shown to make more MERS-CoV RNA than any other cell line tested and the second greatest quantity of viral particles (after goat cells).

Check out Eckerle et al. over at the CDC's Emerging Infectious Diseases journal for a very nice graphic.

This may be an artefact of the adapted cell-line....but let's not forget to test those baboons hmm?

A model of MERS-CoV acquisition (ver1)

With thanks to David Spalten (@dspalten) for discussion and considerations and AtRG for advice.

First we heard about Middle East respiratory syndrome coronavirus (MERS-CoV)-related viruses in bats in South Africa, then we read of antibodies in camels that reacted to MERS-CoV more than the most likely (known) other CoV to infect cattle, and most recently we were absorbed by the discovery of a probable parental strain of the MERS-CoV in the faeces of a Taphozous perforatus insectivorous bats.

We've also heard that most patients have not had direct or obvious contact with bats and we also know that pasteurised camel milk products should be safe. But that still leaves many stones unturned.

So if we can assume that the most likely route of acquisition of MERS-CoV is through the upper respiratory tract and that the spillover events come from animals (I'm including human-to-human exposures in this figure) then we need to consider how that might happen. I've included the animals above as well as baboons as they seem highly mobile, interact well with humans, visit mountains and caves (where bats are likely to hang out") and are found in the KSA. I've added ingestion but I don't really imagine how this could result in a respiratory infection, and MERS-CoV gastrointestinal involvement seems infrequent.

I don't live in the Kingdom of Saudi Arabia or in the Middle East and I do not profess to know much of the environment so what follows is "remote guestimation" at best. But I've thrown together some of the possible routes and animal players into a figure which may have some degree of reality buried in there somewhere. It may also spark an idea or two among those who do know what they're talking about.

So, here is my model of how humans may indirectly get a zoonotic infection from a primary or secondary animal host...

A model of MERS-CoV acquisition. Click to enlarge.

I'd be most happy to take suggestions for improvement of the figure. I know some of you like to use the graphics from the blog and Virology Down Under (which I strongly support, asking only for a specific reference to their source) so if they can be made more robust, I am very happy to do so. Get to me via the comment section below or on Twitter (see top right).

Baboons and MERS-CoV....

This post is based on @dspalten and his interest materials and analyses

Twitter yields all sorts of things to think about. Since the Lancet article on MERS-CoV-like antibody reactivity in dromedary camel sera, one tweeter has been a strong proponent of testing baboons, an African and Arabian old world, omnivorous monkey, for MERS-CoV.

A troup of Hamadryas Baboons (Papio hamdryas) in the
mountains , Saudi Arabia.
Hamadryads live for 30 to 35-years
Image from [3]

While there is probably a very long list of animals that humans may come into contact with that could be the primary or secondary host of MERS-CoV, I've listed some of the points and references (some websites at the bottom) supporting why we should add baboons to that testing list:

• Baboons roam the horn of Africa (mid-eastern) and the southwestern Arabian peninsula including Yemen and the Kingdom of Saudi Arabia (KSA). They can climb trees.
• They are highly adaptable to environmental change and will make use of human communities for food
• They are known to acquire, harbour and suffer from, a number of bacterial and viral infectious diseases that affect humans and their fellow primates. These include tuberculosis, Salmonella , Shigella, Cryptosporidium, and viruses including HIV-2
• In Africa, humans self-report baboon exposures to include:
• Baboon to human:  eating baboon leftovers, from contact with faeces, screaming/breathing near humans, contamination of water sources, biting insects/flies
• Human to baboon: contact with sick people, bad sanitation/hygiene/human wast disposal, insect bites/flies
• Coronavirus particles were visualized in 1982 by Smith and colleagues baboon faeces from baboons and primates (some with diarrhoea/gastroenteritis, but no association). 
• Persistent excretion was noted
• The CoV-like particles did not grow on Vero cells at that time (MERS-CoV does)-because a picornavirus outgrew them (I hate it when that happens!). 
• Weaned animals had a higher prevalence of CoV particles than unweaned primates
• Other viruses found in these animals by this group of researchers include adenoviruses, herpesviruses, picornaviruses, bacteriophage and an unknown virus particle
• Signs of a spontaneous CoV outbreak in macaques and baboons was reported in a Russian (non-English) publication in 1994 by Goncharuk and colleagues. The spontaneous monkey CoV outbreak in an animal house was due by a CoV that serologically cross-reacted with the human CoV OC43. Cases were associated with pneumonia and enterocolitis.
• Another Russian article in 1986 by Shevtsov an colleagues also notes monkey involvement in an animal nursery
• Memish and colleagues noted in an article about Alkhurma haemorrhagic fever virus (AHFV) in the International Journal of Antimicrobial agents in 2010, that baboons could be found in the populous Makkah  (Mecca) region. While AHFV cases had been noted in this and other regions of the KSA, and may be occurring in baboons, no active surveillance was being carried out  for this virus.
• Drewe and colleagues described in an article in 2012 in Emerging Infectious Diseases, the infections spread between baboons and baboons and humans in Cape Town, South Africa. These baboons, Papio ursinus, are a tourist attraction, coming into frequent contact with humans. 
• The animals were seropositive for, or cross reactive to, cytomegalovirus and Epstein Barr virus (herpesviruses) and hepatitis A virus (HAV). 
• The authors noted concerns about HAV which us transmitted via the faecal-oral route and the fact that 6/7 urban were HAV seropositive while 0/8 forest baboons had antibodies.
• The data suggested a low risk, but a risk nonetheless  for zoonotic transmission of viruses

So we know that baboons are in the KSA area, they can harbour human or human-like viruses including possible coronaviruses, they adapt well to changes in their environment, they are highly mobile, they are not afraid of humans and they can be found in close contact with humans and areas of human habitation.

Definitely worth considering if anyone is getting around to some serious hunting for the source of MERS-CoV or other viral disease sources...or just for virus hunting in general. Great way to fight of the next pandemic would be to find the virus and source before we become the sentinel species of it's spread (hat tip to Crof). 

This also plays into the concept of "One Health" which recognizes that more than half of human infectious diseases originated in animals.

Just for the record, in case anyone interprets this or my posts on camels in such a way, I do not advocate the culling of an animal species because it is or may be a carrier of MERS-CoV. 

I do advocate quick reactions to create practices that reduce the risk of exposure to such animals. That is something that can be achieved in the interim while more scientific data are collected, even if we are not 100% certain of the transmission picture yet (if one can be 100% certain about anything in a biological system). 

I really don't think we need to go to the other extreme and decry new findings, such as those in camels, when we don't yet have enough data to prove or disprove their role in MERS. 

Education into reducing the risk of exposure may be the quickest and easiest way to minimize new MERS-CoV cases. In the meantime, expanded testing of other animals might help find the source.

1. http://bwindiresearchers.wildlifedirect.org/2011/05/30/raiding-baboons-and-disease-risk/
2. https://www.google.com.au/url?sa=t&rct=j&q=&esrc=s&source=web&cd=3&ved=0CDYQFjAC&url=http%3A%2F%2Fwww.itfc.org%2FWorkshop2011%2FPresentations%2520day%25201%2FBaboons%2520as%2520Potential%2520Reserviors%2520of%2520Pathogens%2520around%2520Bwindi%2520INP.pdf&ei=51oJUpqMEKqiiAe6ioCgCw&usg=AFQjCNE66l7isro843JpGDAJboZQm1tXRg&bvm=bv.50500085,d.aGc
3. http://biology.stackexchange.com/questions/8231/what-is-the-name-of-the-baboons-that-live-in-saudi-arabia