Bird Flu: More Common, Less Deadly than We Thought?

A new study suggests H5N1 is more easily spread and far less deadly than scientists believed. What does that mean for work on potentially lethal man-made versions of the virus?

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This is one thing we thought we knew about the avian influenza virus H5N1: it is extremely deadly. Since the virus first emerged widely in human beings in 2003, there have been 587 cases confirmed by the World Health Organization (WHO). Of them, 346 resulted in death. That’s a fatality rate of 59%, far above the 0.1% death rate for the standard seasonal flu. If H5N1 really kills more than half of eople it infects, it would represent one of the most dangerous health threats on the planet.

This is another thing we thought we knew about H5N1: it rarely infects human beings. Though the virus can spread like wildfire through populations of chickens and other birds, it almost never seems to make the jump to infect human beings — and even then, only when there’s close contact between an infected bird and a person. (Like the Thai cockfighting trainers who became infected after giving mouth-to-mouth resuscitation to their sick fighting birds.) The virus almost never spreads from person to person.

That makes H5N1 frightening — especially if you’re unlucky enough to contract it — but, ultimately, a limited health threat. Now, what if it it turned out that H5N1 actually infected far more people than we thought, and that nearly all of them became somewhat sick, but ultimately recovered? That would mean H5N1 was much more transmissible than scientists expected, but far less deadly.

That’s the conclusion pushed by a paper published in this week’s Science. Peter Palese — an eminent flu expert at New York’s Mount Sinai School of Medicine — and his colleagues did a meta-analysis of 20 studies that attempted to find evidence of subclinical (meaning without symptoms) infections of H5N1. He estimates that H5N1 infection is far more common than the number of laboratory-confirmed cases would indicate, and that the true fatality rate is much, much lower than 59%. If that’s true, bird flu may not be the great danger it has sometimes seemed to be, and that would make the ongoing debate over whether scientists should continue work on a man-made H5N1 virus simply academic.

MORE: A Bird Flu Death in China — What It Means, and Doesn’t Mean

Many flu researchers have long assumed that there were likely more human H5N1 cases than were being officially confirmed. The WHO counts only cases that involve people who come to the hospital and who can be confirmed through blood studies to have contracted H5N1. In a developed country like the U.S. with an extensive hospital network, doctors might be able to catch most of those infections. But nearly all the human cases of H5N1 have taken place in developing countries like China, Thailand, Indonesia and Egypt, and often in rural areas where doctors and hospitals are in short supply. (To get an idea of the challenges faced by health officials fighting H5N1 in a poor and sprawling country like Indonesia, check out my 2007 TIME Asia story.) There’s every reason to believe that many H5N1 cases might be missed — especially unusually mild ones that wouldn’t drive an infected person to the hospital.

So scientists have tried to conduct seroconversion studies in areas where H5N1 has hit, looking for evidence of antibodies to the virus in people’s bloodstreams. The Science article analyzed data from a number of those studies that involved more than 12,500 subjects, and found data to suggest that 1% to 2% of them showed seroevidence of prior H5N1 infection. Though Palese and his colleagues — who refused to comment for press stories on the study — wouldn’t say what the revised fatality rate for H5N1 would be, their data suggests that the new rate would be less than 1%, which would make it only a little more dangerous than the seasonal flu.

But not everyone agrees with the paper’s conclusions. The WHO has stood by its data, estimating that the fatality rate for H5N1 is likely between 30% and 60%. Other experts criticized the Science study, arguing that it was based on misleading or faulty data that may overestimate the number of people infected by the virus. A recent analysis from Michael Osterholm, head of the University of Minnesota’s Center for Infectious Disease Research and Policy (CIDRAP), estimates that the fatality rate of H5N1 is at least as high as the WHO has put it. From CIDRAP:

Yi Guan, MD, PhD, a virologist at Hong Kong University, told CIDRAP News in an e-mail that he believes H5N1 seroprevalence rates are likely to be lower than what many studies have reported. He said microneutralization assays can generate a lot of false positives, based on his lab experience comparing the method with classical virus neutralization assay.

Conducting serological surveys using microneutralization assays without doing parallel tests to confirm the findings can produce H5N1 seroconversion rates amplified “many, many times or log,” he wrote.

Guan said he personally has doubts about whether there are any subclinical H5N1 cases, based on his own experience reviewing unpublished data.

The debate over H5N1 is more than just academic, however. The flu world is currently enmeshed in a deep debate over whether research involving a man-made H5N1 virus — one that apparently looks to be most highly transmissible and highly deadly — should be published in scientific journals. Those who oppose publication argue that putting the details of such work in the public realm increases the likelihood that terrorists will try to recreate their own killer flu. There’s also the chance that if work continues on the virus, it might escape from the lab — as happened several times with the SARS virus — triggering a potentially catastrophic pandemic. Those in support of the research, however, argue that such work helps flu experts prepare for a possible pandemic — and they say that the government has no business trying to censor legitimate scientific research.

MORE: Should Journals Describe How Scientists Made a Killer Flu?

Last week scientists and public health officials from the WHO at a highly contested meeting in Geneva agreed to put a temporary halt on any work on the man-made H5N1 flu, while the journals Science and Nature — which have accepted manuscripts on the research — have agreed to hold off publishing studies on the virus for now. But both journals have said that they eventually intend to publish the studies, and many flu researchers including Palese have said that they believe fears of the man-made H5N1 are overblown. And if it turns out that the natural H5N1 virus is actually much less deadly than we thought, the entire controversy could be defused.

That makes the timing of the Science study — published right after the WHO meeting — suspicious to some flu experts, as Sharon Begley wrote for Reuters:

Some scientists said there was little coincidence in the timing of the study’s publication. They noted that Palese published similar findings last week in the journal Proceedings of the National Academy of Sciences and that it is unusual for Science to publish a paper when key data have appeared elsewhere.

“The editors of Science and Nature are the most powerful people in science,” said an influenza epidemiologist who asked not to be named for fear of retribution. “This is the editors of Science saying H5N1′s fatality rate isn’t 50 percent, so we don’t need to worry about a (possible) lab release.”

For its part, Science denies that the controversy played any role in the decision to publish the Palese study. But either way, the debate over H5N1 — the version in nature and the one that was cooked up in the lab — is far from over. And to those who’ve already made up their mind: don’t count your chickens before they’re hatched.

MORE: A New Project to Track Animal Diseases Before They Infect Humans

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