Saturday, 19 April 2014

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 do know 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.