By Tara C. Smith
IOWA CITY — Water birds, to an influenza researcher, are more than majestic swans and charming mallards. They are instead stealthy vectors of novel influenza viruses, some of nature's bioterrorist agents, chauffeuring dangerous microbes from place to place without showing symptoms of infection themselves. Wild waterfowl are reservoirs for every imaginable combination of influenza viruses, though the vast majority of those viral cocktails don't seem to infect humans.
However, spillover of bird viruses into the human population is a numbers game. With billions of birds hosting an uncountable number of permutations of influenza strains, it's inevitable that once in a while, one of these combinations will evolve the ability to replicate in humans. This has happened with an influenza type known as H5N1, the "bird flu" that the world has been watching since it was first isolated from human infections in Hong Kong in 1997. In the past 16 years, H5N1 has caused more than 600 infections in humans and almost 400 deaths — killing approximately 60 percent of those who are known to have been infected with this virus. Luckily, H5N1 hasn't evolved the one thing that is critical for kick-starting an influenza pandemic — efficient transmission between humans. Instead, most patients probably acquired the virus from domesticated poultry, such as chickens and farmed ducks.
While we were carefully watching H5N1 in Asia and Europe, another influenza virus — 2009 H1N1 — appeared seemingly out of nowhere. Ultimately traced back to swine, this virus was easily spread between people, but unlike H5N1, it wasn't any more deadly than our normal yearly influenza viruses (which, it should be noted, still kill on the order of 36,000 Americans each year). And now, while we're still working on understanding how H5N1 and H1N1 have jumped between species, yet another influenza type has surfaced: H7N9.
Like H5N1, H7N9 appears to be an avian virus. First identified in humans last month near Shanghai, it's now infected at least 24 people in four of China's provinces; seven of them have died, according to official World Health Organization numbers. (Other sites are reporting as many as 33 cases and 9 fatalities). So far, we haven't seen any evidence of sharing among humans, which is a good sign, though some possible family clusters are being investigated. And while there's some concern that Chinese hospitals have been covering up possible cases of the infection (as happened during the early weeks of the SARS outbreak in 2002), Chinese authorities do appear to be proactive now that the outbreak is international news. The Ministry of Agriculture released findings of H7N9-positive pigeons from a marketplace in Shanghai, which led to a cull of poultry from that market in an attempt to stem new human infections. In some places, markets have been shut down. With H5N1, most infections have been in people with direct contact with live poultry, either in marketplaces or on poultry farms. These outbreaks are devastating for Asian poultry producers, who house approximately 4 billion chickens and are already feeling the sting of the H7N9 outbreak.
One reason to worry about both H5N1 and H7N9 is that the data we have on infections and deaths are available largely because they have made people very ill — ill enough to seek treatment at a hospital. As you might imagine, calculating infection and death rates based only on hospital data — where you'll find the sickest of the sick — is kind of like asking if someone in the vicinity of Yankee Stadium on game day is a baseball fan. You've artificially enriched your population with baseball lovers, so you may find that 95 percent of the population adores the sport — numbers that wouldn't hold up if you'd sampled more randomly throughout New York City. So, in reality, H5N1 (and possibly H7N9) likely don't have death rates of 60 percent and 30 percent, respectively. But we're probably missing more human cases — baseball fans who didn't make it to the game — which means that there are more spillover events from birds to humans than medical authorities are picking up. With H5N1, when researchers have gone to look for these undocumented infections, results have been mixed. Some groups didn't find mild or asymptomatic cases, while others found people who did have evidence of prior infection with H5N1 (they carried antibodies which suggested their bodies had seen the virus sometime in the past) but no evidence of clinical illness with symptoms befitting H5N1. If and when larger-scale studies of H7N9 are conducted, we'll probably see the same thing: It's likely that more people are being infected than are becoming seriously ill, but the mild or remote cases just aren't showing up on the radar of those who are doing surveillance right now.
This is one of the major challenges of working with emerging infectious diseases. As an epidemiologist, the most important thing I try to do is prevent disease — it's much easier to keep that genie corked than to get it back in the bottle. However, with diseases that jump between animals and people — "zoonotic" diseases — we usually don't find that they've moved into the human population until they make someone sick enough to see a doctor. By that time, it may be too late; the microbe may have already become established in the population, adapting to humans stealthily before we were even aware of it. This is probably what happened with the novel H1N1 influenza, and what scientists fear may be happening with other germs all over the world.
It probably seems that there are more unknowns than known quantities with avian influenza viruses. This is not far from the truth. But what we do know without a doubt is that avian influenza viruses will keep jumping species barriers — to humans, to pigs, to other mammals. Some of these may be deadly, ongoing spillover events, like H5N1's repeated reappearance in the human population. Some may be seemingly one-time events, like the avian H7N7 virus that caused a large outbreak of conjunctivitis and one fatality in the Netherlands in 2003. It remains to be seen how the current H7N9 outbreak will play out, but one thing is certain: This won't be the last novel avian influenza virus to infect humans.