Liberia gave Ebola the boot...and a virus may soon be removed from the wild

The people of Liberia have earned our respect, some time for national celebrations and frankly any other rewards that may flow from denying the Makona variant of Ebola virus any hosts among their community. 

The world considered this viral species to be one of the list-toppers when it came to ranking the causes of the most scary acute infectious diseases. Ebola virus has been the basis for all sorts of 'end-of 'the-world' mutating virus horror movies, books, and TV shows. It's not at all surprising that the public view of an Ebola virus infection had long been one of blood, fear and terror.

Figure 1. The decline of the Makona variant of
Ebola virus in Guinea, Sierra Leone and Liberia
(now free of EVD transmission).
Click on image to enlarge.

Behavioural change was a major factor in reducing virus transmission in Liberia. Alongside that was a broad range of aid given from within and beyond Africa's nations. By working together, a widespread outbreak that was not initially thought likely to happen at all, was routed. 

For now. 

Liberia is not immune to new cases of Ebola virus disease (EVD) crossing its borders or popping up due to a new animal-to-human jump (a zoonosis). That could happen any day - it might be happening now. But those who are still on watch will be searching out new cases while the remaining sites of transmission - Guinea and Liberia - do their best to deny Ebola virus a chance to replicate and spread. The people of Liberia will keep watch help because they have learned very tough lessons about viruses, epidemiology and communication. At least 10,604 suspect, probable and confirmed EVD cases, 4,769 deaths and way too many stories of sadness and families destroyed are a very strict teacher. 

Figure 2. The number of confirmed EVD
cases (yellow) grinds to a standstill. Only
9 cases in the week to 10th May 2015.
Click on image to enlarge.

The crude prediction in Figure 1 suggests that zero cases across all three countries could happen at the end of May, but many stars must align for that to be a real event. 

Human factors - the causal and sustaining variables of any outbreak of infectious disease in humans and sometimes animals - remain very much in play. But once that tri-country zero case value is attained, we have 42 days of watching and waiting - from the time the final case tests negative. 

New cases may arise from sources as-yet-unknown. But even if they do keep popping up, it seems very unlikely that widespread transmission will amplify to earlier levels (see the steep slopes in Figure 2) unless a major lapse in attention occurs. Hence,the need for continued vigilance - and Liberia remains on alert for a further 90 days. That more recent figure comes about because we know that infectious Ebola virus can persist in some body sites for many weeks after signs of disease have passed. Whether that virus reservoir is present in every person and whether it actually does cause new Ebola virus infections remain unproven. When you consider what can happen when one person gets infected by an Ebola virus in a tiny remote village in a country that is ill prepared to cope with it and has traditions that lend themselves to its spread...even minor risks rightly come under more intense scrutiny.

What next for this particular virus though? The only place where the Makona variant of this member of the Zaire ebolavirus species will soon exist, is in the freezer of (hopefully) very biosecure laboratories in the US, UK, Africa, Russia, China and probably other laboratories in countries that hosted, evacuated or repatriated cases of EVD. 

There is no sign at all - and this is because of the continued efforts and focus of many currently working throughout west Africa - of the fabled "endemic Ebola" becoming a reality. Unless you mean enzootic 'Ebola'- in which case , it already is, I suspect. It seems very, very likely that the forests of west Africa continue to shelter animal hosts with less mutated versions of this and other ebolaviruses (and filoviruses and who-knows-what else). The host species and route(s) of transmission to humans are yet to be confirmed but for now, we are not too far off eradicating one unwanted viral scourge from the wild. Impressive what we can do when we pull together.

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Watching zoonoses evolve...

Special guest writer: @influenza_bio

For the first time in human history, we are watching diseases jump from animals to humans on a large scale. We've seen diseases appear for the first time in humans before; that's not new. We've seen HIV and several new strains of influenza emerge over the past century or so, for example. What is new is that we can now watch this process as it happens. We are able to watch animal diseases trickle case by case into humans, and we wonder whether any of these diseases might some day become human diseases. We wonder whether we might be watching pandemics develop in real time.

A disease that jumps from a non-human animal to a human (or the other way around) is called a "zoonotic" disease or a "zoonosis." Individual cases are called "zoonotic" cases. When a zoonotic disease is trying to make the jump to us permanent, we call this disease an "emerging infectious disease."

We have certainly been watching a lot of zoonotic MERS coronavirus and bird flu (e.g., H7N9 and H5N1) cases develop in people lately, along with Ebola virus cases. Zoonotic cases of other diseases, including infections with various strains of bird and swine flu, occasionally develop, as well, and are watched closely.

When the 2009 H1N1 flu pandemic started, we had no clue much beforehand that it was on its way.  We didn't even have surveillance data about swine flu strains that were even particularly close to the strain that emerged in us. A large animal flu surveillance gap blindsided us that year.

And we will undoubtedly be blindsided again by other emerging infectious diseases that we won't even see coming, although people are doing their best to see what's out there.

When an emerging infectious disease jumps to humans, it can cause either a relatively local outbreak or a worldwide outbreak, called a "pandemic." If a disease becomes a pandemic, that just means that it's spreading worldwide; the word "pandemic" doesn't imply anything about how bad the disease might or might not be. In some sense, the worst case can be when a disease jumps to humans and becomes "endemic" in humans, meaning that it gets established in people and regularly infects people, year after year. Endemic diseases can circulate worldwide (e.g., influenza) or in more restricted geographical regions (e.g., malaria).

Our knowledge and resources have grown to the extent that we are currently able to monitor some significant zoonotic outbreaks of disease. We are currently watching the MERS coronavirus and the influenza A(H7N9) virus both try to become human viruses.

Will either one succeed? We can't say. We've never watched this process happen before. We don't know how long such a process "usually" takes, or whether there even is a "usual" amount of time that it takes. We don't know how long it might take, or how quickly it has happened before. We doknow that the process is "stochastic," meaning that it involves a lot of chance. A pathogen that in one situation might cause a pandemic might just die out in another situation. Everything depends on the specific changes in a pathogen that get a chance to develop and on whether those changes end up getting passed on. We don't know how often pathogens "fail" when they "try" to make the jump to humans.

A lot of us have watched the recent surge in MERS coronavirus cases with some amount of concern. As of April 19, 2014, there are two large clusters of cases in the Middle East, and at least one of them is still growing. One cluster, in Jeddah, Saudi Arabia, now has 60 cases; 7 cases were added to this cluster today, and 6 were added yesterday. There are perhaps over a dozen cases in another cluster in the UAE. One patient who became ill with MERS in Jeddah at the end of March flew to his home country of Malaysia while ill and subsequently died in Malaysia; 79 of his contacts are now being watched closely in Malaysia. Test results are starting to come in for a number of these contacts, and thankfully all are negative for MERS so far. An asymptomatically infected Filipino health care worker traveled on an airplane back to the Philippines a few days ago. Yesterday, a MERS case was announced in Greece; a Greek man who had been living in Saudi Arabia was recently in Jeddah and presumably became infected there before flying back to Greece. He arrived in Greece with a fever; his contacts are now being monitored. In other words, MERS case numbers are growing quickly right now, at least in part through human-to-human transmission, and infected � and potentially infectious � patients are getting on airplanes to travel around the globe.

Does what we're seeing now represent changes in the virus that are making it more transmissible among humans? Or are we seeing a random fluctuation in the numbers of cases? Or, are we seeing more cases simply as a result of improved surveillance? I would argue that what we're seeing likely reflects one or more changes in the virus, simply because

1. We've been seeing so many more symptomatic cases recently, 
2. We've been seeing significantly larger clusters than we've ever observed before,
3. A greater number of health care workers appear to be getting infected than ever before, and
4. A greater proportion of cases are in health care workers than ever before. 

It's not that we've been seeing a rise only in the number of asymptomatic cases detected, which could suggest that we're only seeing the effects of improved surveillance. Moreover, while surveillance does seem to be picking up more mild and asymptomatic cases, it is difficult to know whether we are seeing more of these cases because of improved surveillance or because there simply are more such cases now. A lot of variables are being changed at the same time, and we don't have perfect information.

Nonetheless, the sheer numbers of recent cases suggest to me, at least, that the virus is changing and becoming more transmissible among humans. Until recently, we rarely saw evidence for human-to-human transmission of MERS; most cases may have been zoonotic. Now, however, large clusters involving roughly 1 to 4 dozen people are being seen, with single infected individuals infecting possibly up to a dozen or more other people. This is new. I don't think that we're seeing these clusters just as a result of improved surveillance, although I would be very happy to be wrong.

What does the future hold for MERS? We can't know. We might be watching MERS become a pandemic, and we might not. We might be watching the current relatively small MERS outbreak develop into a larger outbreak that eventually gets contained, as was seen with SARS. Or, the whole outbreak might all just simmer down or go away. Even if the virus were currently changing to become more transmissible, the current spate of cases could still simmer down or go away, just stochastically, just through sheer chance.

Prudence would dictate that we remain concerned and vigilant, however, especially as symptomatic MERS cases have had an approximately 40% case fatality rate (CFR). If MERS did cause one or more wider outbreaks in humans, that CFR might or might not change. Even if the CFR dropped to 10% of what it is now, it would still be on the same scale as the CFR for the 1918-19 influenza pandemic.

As a global society, we have an obligation to do everything in our power to prevent the MERS coronavirus from causing larger disease outbreaks in humans. We need more surveillance in affected countries, including much more genetic sequence data. And in countries of the Arabian Peninsula that are currently detecting MERS cases, infection control procedures need to be improved to the point where nosocomial cases in health care workers and patients are prevented. Health care workers in other countries should be educated about the possibility of MERS patients arriving from afar and about how to treat such patients safely. If this virus becomes more transmissible, we should not be caught unprepared. We can see this one coming.

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Got a spare $6.3-billion? Experts could use it to discover the missing 320,000+ mammalian viruses we don't yet know about

...or just $1.4-billion for 85% of those. And that's not including the non-mammalian ones. This is according to a new paper in mBio today by Andrew and colleagues from a collaborative team including Prof Ian Lipkin, from Columbia University's Mailman School of Public Health. 

The study advocates for a much more structured, systematic approach to discovery and notes that existing studies, such as the U.S. Agency for International Development's (USAID) Emerging Pandemic Threats (EPT) program including the PREDICT project (more detail in Lancet article here), have made headway into the list already. Each adding valuable assets to our virology intelligence archive.

Finding these viruses, and the animals they reside in, is key to limiting zoonoses. Sure, discovery does not equal simultaneous cure, but ignorance does equal surprise outbreak and death. Most emerging human infectious are caused by animal viruses infecting us. This is well defined by the One Health concept which promotes investigation of all aspects of the network of links between humans and their hairier, more leggy or winged co-habitants.

If we ever want to get ahead of the curve, investing in this sort of research is essential to allow us to know our enemy. It let's us be ready to meet them at the door instead of scrambling to action when they kick our door in! And it is a scramble; just look through the literature and media surrounding any virus that has spilt over from animals to humans in recent decades....a degree of controlled panic over the many things we don't yet know in the early stages of an unexpected emergence. For example: 

• We'd have no laboratory testing methods (culture, PCR or serology) nor the procedures to confirm weird results.
• Which country would "own" the virus, what would we call it (mock you may, but a lot of electrons and ink have been wasted on that story for the MERS-CoV for instance) and how long would it take before commercial detection kits were available (for MERS-CoV - its been nearly 15-months since the first cases in Jordan and still nothing well validated and widely available for use by non-reference laboratories)?
• When would we have enough of the virus to make positive controls for those tests or to kick off research into how the virus does what it does?
• We don't yet know what it does! What is the clinical spectrum of disease, how big is the iceberg let alone it's tip; what are the signs and symptoms; what does it do in different patient groups - those with and without comorbidities, different ages and sex?
• What is the proportion of fatal cases?
• Where did the invader came from?
• How best to handle the pathogen in hospital settings
• How fast and to how many does each case transmit (it will be a while until we can calculate the R₀)?
• What drugs do we already have that can moderate disease?
• How long will it take for an antiviral or vaccine, if they can be prepared, to be available and how long thereafter will antiviral resistance become an issue?
• How many that the virus infects will die?
• Does the virus interact with other viruses, bacteria, fungi or parasites?
• Does it have a peak season and is that affected by the environment?

Pretty much ALL of these things can be addressed if we invest in finding the culprits, their host and begin to unravel how they tick sooner rather than (too) later. Sure, they may never spillover, but when just 1 does, the impact is felt around the world, be it from loss of life, financial instability, healthcare burden, travel and tourism decline, animal culling or just a global feeling of insecurity. Any 1 virus outbreak can wield a lot of power in today's highly interconnected world. 

Count VDU in the cheer squad for this sort of proactive research. Money well invested.

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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) outside
of Riyadh, Saudi Arabia. Hamadryads live for 30 to 35-years
Image from Northwest Wildlife Homepage.

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 recognises 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 minimise new MERS-CoV cases. In the meantime, expanded testing of other animals might help find the source.

• http://bwindiresearchers.wildlifedirect.org/2011/05/30/raiding-baboons-and-disease-risk/
• 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
• http://www.northwestwildlifeonline.com/Saudi%20Arabian%20Wildlife.htm
• 
  

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