Tuesday, November 5, 2013

Measles, Cows and an "Oh crap!" Moment

In the history of the battle against diseases, there are only two that have been completely eliminated from the wild. Smallpox had been with us for millennia, but it wasn't until sometime around the 17th century that moderately successful attempts at preventing the disease were practiced in the form of variolation, or inoculation with pus from an infected individual. This practice, though effective, carried significant risks, such as actually causing the disease or infection with some additional disease, like syphilis. Then along came Edward Jenner, who discovered that those infected with cowpox appeared to be immune to the more dangerous smallpox. He developed the first rudimentary vaccine in the late 18th and early 19th centuries. As medical knowledge advanced, the vaccine was refined and improved, reducing (though not eliminating) the risk of adverse effects and improving its effectiveness through booster doses. In 1967, a worldwide campaign was begun to eliminate the disease from the wild, with the last known wild case of smallpox occurring in Somalia in 1977, making it the first disease eliminated through human efforts.

The second disease that we have managed to eradicate from the wild is rinderpest, a morbillivirus closely related to human measles virus. Rinderpest was once a scourge of cattle. As with smallpox, innoculation was an early attempt to control the disease. Unlike smallpox, inoculation never really caught on, partially due to lower efficacy. Jenner's successes with vaccination using cowpox led to unsuccessful attempts to use cowpox to prevent rinderpest. Vaccines using the rinderpest virus were developed in the early 1900s, yet despite the development of effective vaccines, control efforts often took the form of wholesale slaughter of livestock when outbreaks occurred. Regional efforts at eradication of the disease began in the 1920s, but coordinated global efforts wouldn't come about for several decades. Ultimately, widespread vaccination efforts led to the last confirmed case in 2001 in Kenya. Vaccination continued for several more years, as experts suspected the virus could still be circulating among wild animal populations. In 2011, with no other cases appearing, the World Organization for Animal Health declared the disease eradicated.

We know that in the right circumstances (like when a disease is limited to a single species), and with enough effort, we can eradicate diseases. But what if a disease jumps species?

That's the question that popped into my mind when I read a news story about measles in cattle in Botswana. My first reaction was, "Oh, sh*t! That's not good." As far as we know, measles virus (Rubeola morbilivirus) can only be sustained in human populations. While it can infect non-human primates, it's not easily transmitted. Humans are the only known reservoir of the virus, which makes it a likely target for eradication. But if it were to establish a reservoir in some other animal? That would make eradication much, much more difficult. My initial alarm was tempered as I looked into the story a bit further and discovered that the term "measles" is also used to refer to a parasitic infection, the tapeworm Cysticerus bovis.

With that "oh crap!" moment averted, I still wondered, "what if?" The current goal of eradicating measles by 2020 is feasible, with proper logistical, financial and political support (though antivaccination activists are threatening this effort), but could the virus jump species and develop a reservoir outside of humans? If it did, what ramifications would that have?

The first question to deal with is: could measles jump from humans to other species? Yes, it is possible, though how likely, I'm not sure. The closest relative of the modern measles virus is rinderpest, hence my concern about measles infecting cattle. And it turns out that measles and rinderpest viruses diverged not all that long ago, probably during the 11th or 12th centuries. Whatever the common ancestral virus was, its evolutionary "offspring" mutated to the point that rinderpest virus stayed pretty much among ruminant animals like cattle, oxen and the like, while measles virus adapted to primarily infect humans in a form capable of maintaining sustained transmission. And while measles has been documented to infect non-human primates, it doesn't appear to be endemic among wild non-human primate populations, with infection and small outbreaks being triggered by contact with humans. The most likely candidates for measles to jump species would probably be crossing to livestock (due to genetic similarities between measles and rinderpest) or to non-human primates (due to genetic similarities among primates).

Measles virus jumping species is possible, but how probable is it that it would establish a non-human reservoir (i.e., sustained transmission among non-humans). With non-human primates, it is probably not all that likely, as the virus tends to be quite deadly in these populations, and the populations are generally not large enough to sustain the virus in circulation. Cattle might prove an easier target, however evolution of the measles virus may prevent infection of cattle. I was unable to find any evidence of cattle being infected with Rubeola morbillivirus (measles virus). The virus has probably changed enough that while it might be able to infect cattle, it may not cause any symptoms or sustain transmission. Research into cross-species transmission relies very heavily on the genetic similarity of the two species. For our two candidate populations, non-human primates represent a like candidate due to genetic similarities, but their distribution and contact with humans is generally lower, while cattle have a lot of contact with humans (i.e., more opportunity for infection), but are not genetically similar, meaning that virulent infection is unlikely.

Let's suppose, though, that the measles virus could jump species, cause illness, and sustain transmission outside of a human reservoir. Given enough time (we're talking at least centuries), this could happen eventually, but let's imagine that it could happen right now, like in that news story that first had me worried. Could the virus mutate in the non-human animal species, possibly combining with some other virus, to create a disease that would devastate the human race (well, more so than measles already does in the absence of vaccines)? In the short term, this is not very likely. Measles, it turns out, is a very stable virus, with highly conserved proteins. That's part of the reason that the vaccine against it is so effective. On its own, it probably would not mutate in a way that would make it deadlier to humans. But could it combine with some other virus? That's also not particularly likely. Viral recombination is tricky. First, the two viruses would need to have similar regions of DNA or RNA. They would need to match up to allow swapping of genetic material. If they aren't similar, then they can't trade genetic regions very easily. But even if they could, there's a good chance that the alteration would render the new virus incapable of infecting host cells or replicating. This hampering of the virus could be due to changes in the surface proteins, errors in the regions that code for replication or alterations in the shape of the virus. With all of these difficulties, even though there is a hypothetical possibility that the virus could successfully infect a non-human animal, cause sustained transmission, and recombine with some other virus, the probability that this would lead to something we need to worry about is so close to zero that we can safely dismiss it as something we wouldn't need to worry about.

Despite all this, I entertained myself with the idea of measles establishing a reservoir outside of humans and the possible ramifications that would have. This was partly driven by the news story, partly by recently reading the Newsflesh trilogy, by Mira Grant (highly recommended, if you like zombies and virology), and less recently reading The Hot Zone, by Richard Preston (also highly recommended). First off, if measles managed to jump species, that would make eradication a whole lot more difficult. Eradication is currently feasible within our lifetimes (or at least within our children's lifetimes), assuming countries get on board with widespread vaccination efforts. If we succeed, that's one more vaccine that can be taken off of the recommended vaccine schedule. But if it establishes a non-human reservoir...that goal suddenly looks a lot less achievable, especially if the species it jumps to is something more remote, like non-human primates. We can vaccinate livestock, but vaccinating wild primates is a hell of a lot harder. But what if measles could not only jump species, but also successfully recombine with some other disease, like Ebola or Marburg viruses, and make the jump back to humans. The result would be horrific. I'll just leave it at my initial reaction to the news story above: "Oh sh*t!"

1 comment:

  1. Uhh...too late, HS.

    It already did that.

    Rinderpest (cattle) -->jumps to humans --> Measles is born.


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