Tuesday, April 16, 2013

A comparison of the 1997 H5N1 outbreak and the H7N9 outbreak

Late in 1997 a novel influenza virus began infecting people in Hong Kong and was associated with several deaths. The pathogen was quickly identified as a highly pathogenic H5N1 influenza virus that was crossing the species barrier from chickens into humans.  The response from health officials and specialists was quick and decisive. 1.3 million chickens were slaughtered in the city. Quail, guinea fowl, pigeons and pet birds were also abandoned or slaughter. Over three days the city was depopulated of domestic birds.
The result was no new human cases of H5N1 in the city over the next month. Eventually, the bird markets reopened and life continued on as before. H5N1 was eradicated from the city (for the next 5 years at least). The drastic actions undoubtedly saved many lives and possibly prevented a human pandemic. In total, 18 human cases resulted in 6 deaths.
Fast forward 16 years and we are now looking at a similar situation with the H7N9 virus. Sixteen human infections and 5 deaths from a virus that came from poultry, lead to the shut down of bird markets, and the initiated the slaughter of thousands of birds in an effort to stymie the spread of the virus. This time something is different.
As of this morning (4/16/2013), there are 72 confirmed human cases and 14 deaths. The the cessation of live bird markets and the culling of thousands of birds has not slowed the spread of this virus to humans. Case rates in Shanghai were steadily increasing for the three weeks prior to the closure of bird markets and a week after the closure the rates were drastically reduced (11 cases reported the week prior, 2 reported the week following). However, case rates in other cities seemed to be climbing still, including the spread of the virus to Beijing some 700+ miles away.

Hong Kong

Hong Kong is an island city of 7,000,000 people. Quarantine and poultry depopulation are relatively easy to accomplished when compared to a main land city with more than three times the population and 6 times the land area. The initial outbreak of H7N9 was spread out across several different cities and the spread was facilitated by ground transportation from city to city. The physically isolated nature of Hong Kong probably prevented that and helped keep the H5N1 contained long enough for human intervention to stamp it out.
Differences in the viruses also make the current situation far more difficult to control. The H5N1 was highly pathogenic in chickens. This made finding the source of the virus fairly easy (hint: its the severely diseased birds). The H7N9 shows no signs of disease in the birds that have tested positive so far. To identify an H5N1 infected chicken you need a basic understanding of what a healthy bird looks like and a functioning set of eyes. To ID an H7N9 positive bird you need serology tests, virus isolation, and genetic sequencing. Additionally, the H5N1 virus was not as infectious to humans as the H7N9 appears to be. If the current case rate identification continues, there will be more human cases of H7N9 over three months than there have been H5N1 human cases in the last 10 years.
 Healthy birds.
Not so much.
The good news for now is that the virus still does not appear to transmit from human to human and seems to be sensitive to available drugs (although more tests are needed to confirm this). The demographics of the cases so far are also pointing to a more promising conclusion. Age breakdowns of cases show a skewing towards the elderly, which is typical of influenza outbreaks. The most troubling human outbreaks (H5N1, 1918 H1N1) show a trend of infecting and killing young to middle aged adults as well as the very young and very old. So far H7N9 does not appear to be especially infectious or deadly to the 20-50 year-old age range suggesting a more moderate phenotype.
A recently published article in the New England Journal of Medicine reviews the first three fatal cases in great detail (http://www.nejm.org/doi/full/10.1056/NEJMoa1304459#t=article). They have a potential lineage origin for the genesis of this virus as well as most virulence, receptor specificity, and drug resistance markers. It is a good overview of the early infections (and I think free to read for all). Basic overview: these viruses probably have partial human like receptor specificity, have some markers for drug resistance (but not all), and are positive for most virulence markers in mice. Most of these markers were established in other subtypes of viruses. Some are more broadly established across subtypes (like receptor specificity markers), while others have only been established in certain lineages. This raises the question of how relevant they are, but based on the observations of the natural infection thus far, I would conclude that they are fairly accurate.
One final update: H7N9 was isolated from an apparently healthy 4 year old. This is potentially bad news. On one hand, silent or mild infections that have not been reported would lower the perceived virulence of the virus (14 deaths in 72 cases is terrifying. 14 deaths in 200(?) cases is significantly less terrifying). However, far more concerning is the possibility that silent or mild infections would make quarantining infected individuals nearly impossible. That would also allow the virus ample hosts to further adapt to humans and gain transmission and infectivity functions that it currently lacks and are currently preventing massive outbreaks on the potential pandemic scale.
Don't need to break out the masks yet.
My original feeling on this virus was that it would be a typical avian influenza outbreak in humans. Cause a few to several dozen cases with high morbidity and mortality (due to only severe cases being reported) and then peter out over a couple of weeks.  However, the case rate does not appear to be slowing down and the identification of silent and mild infections  coupled with the geographic spread is very troubling.   It is still too early for the doomsday preppers to start screaming "Told you so!", but I am far more nervous about this virus than I was two weeks ago.

1 comment:

  1. the virus is very poultry-adapted
    in the inner segments. As was the 1997
    Hong Kong virus, a reassortant from chickens.
    It was not in wild birds and they could wipe
    it out. The ~2002 recurrent H5N1 was not so
    much a poultry virus (#amino acid mutations in segment 8 etc.), it was in wild birds and did
    spread and still persists. I think chances are good that they can wipe out this H7N9. Testing must be increased since it's LP, but they can do that.