|SARS S protein evolution (Zhang et al., 2006)|
One of the biggest outstanding questions about the new H1N1 Swine Flu epidemic is the mortality rate. Most of the cases outside of Mexico have been quite mild, whereas there have been a significant number of deaths linked to this flu infection in Mexico. A superficial look at the limited data we have suggests that the virus might be similar to routine human flu (0.1% mortality rate) outside Mexico but more like the 1918 flu (2.5% mortality rate) in Mexico (but note that I don’t believe this is the case!) Why the difference?
Vincent at the Virology Blog highlights a number of possible explanations that boil down to three general categories:
- Different environment – Are people in Mexico City exposed to different opportunistic bacteria? To more pollution? Slower or worse health care? My opinion — possible, but not really consistent with our knowledge about influenza virus.
- Different virus – Is the virus circulating in Mexico the same as we’ve seen elsewhere? My opinion: Although we haven’t yet seen genome sequences from Mexican virus, this is unlikely, because we have seen sequences from patients who presumably caught the virus in Mexico, and these look like all the others.
- Unknown denominator. This is my preferred explanation. As I put this in a comment in a previous post, “I still think the most likely reason for the apparent difference in Mexico and the US is the missing denominator, rather than any host or environmental factor. That is, I suspect that the virus is much more widespread in Mexico City than the authorities know. Because they almost entirely tested severely ill hospitalized patients, it’s not surprising that they found high mortality rates; if they were also testing mild cases (as is happening in the US and elsewhere) I think they would likely find a very widespread infection with a low mortality rate.”
However, I want to throw out one more possibility — not because I think it’s the most likely explanation, but because I think it’s the most interesting explanation, at least to me (and it’s my blog, so I get to choose). (And I’m sure I’m not the first to consider this, by the way — the CDC guys are presumably already thinking about this possibility.) That is that the virus we are seeing now is not the same virus that caused the mortality in Mexico. We are now seeing the human-adapted virus, whereas (remember, still speaking hypothetically) the virus that killed the patients was still swine-adapted. As the virus adapted to humans it became less virulent and better at human-to-human transmission; we are therefore seeing the adapted, lower-virulence virus, and the high-mortality virus has already gone extinct. To test this, we need not only current samples from Mexico, we need samples from the earliest patients they had.
There are precedents for the pieces of this, though I don’t know offhand of an example where both halves have been seen. As an example of rapid evolution as a virus shifts species, there’s SARS virus; it jumped from civets to humans; we saw the genomes of the virus evolving at a furious rate as it adapted to humans. (The figure at the top here shows evolution of the SARS S protein1 – click for a larger version.) Certainly we know that viruses in general change their virulence (in both directions — increased and reduced virulence) as they adapt to a new population.
Some related posts I’ve made:
- Viruses jumping species
- Where did avian flu come from, and where is it going?
- Species-jumping viruses
- Rabbits 1, Virus 1: Evolution of viral virulence
- Evolution to reduced virulence: It does happen
- Increasing virus virulence
… and really, a lot more — this has been one of the major themes of my blog.