Bird flu may be more common and less deadly: Study finds

By Dr. Ananya Mandal, MDFeb 26 2012

The H5N1 influenza virus commonly called “bird flu” or “avian flu” could be more prevalent and less deadly than health officials had thought, according to a new study published online (Feb. 23) by the journal Science.

Till date the World Health Organization (WHO) reported 586 human cases of the H5N1 flu since 2003, and notes that as of Feb. 22, 59 percent (346 individuals) of those people had died. However this mortality rate may be misleading says the new study’s author Peter Palese, chairman of the department of microbiology at the Mount Sinai School of Medicine in New York. That's because the cases reported by WHO include only people who were sick enough to go to a hospital and be laboratory-tested for the virus.

For WHO, to get counted, a person must have an acute illness and fever within a week and test positive for exposure to the H5 protein that gives the virus part of its name. Anyone sick enough to do that is more likely to die to begin with, and in countries where avian flu is present, access to health care and hospitals is patchy says Palese. Basically, there could be a lot more people out there who get the virus and either don't show symptoms or don't feel bad enough to see a doctor he says. “WHO does not account for a majority of infections, but rather the select few hospitalized cases that are more likely to be severe,” says one of the study authors, microbiologist Taia Wang of the Mount Sinai School of Medicine in New York. That could mean an undercount of patients who suffer only minor bird flu illness, inflating the death rate.

For the study Palese and his colleagues looked at 20 studies of H5N1 incidence rates, doing what is called a meta-analysis, or a study of studies. Those studies involved a total of 12,677 people. They found that among that group, which was likely to have been exposed, about 1.2 percent on average were "seropositive" — showing antibodies to the virus.

For all studies the percentage of people whose blood serum showed evidence of a prior H5N1 infection ranged from 0 to 11.7 percent, though the last figure came from people living in close quarters with those who were infected.  But none of these groups includes people who didn't end up in a hospital or clinic.

To translate this to the rest of the population even a 2 percent infection rate is a lot of people in a group of millions. But if the WHO is seeing only those who get to the hospital, it's likely that the number of people with the virus is higher, the researchers say. That means the death rate would be lower.

Vincent Racaniello, professor of microbiology and immunology at Columbia University in New York, said he thinks the study is a good one, and points to the next step of looking at larger populations that aren't going to hospitals. He added that if it turns out many more people are infected than get sick, H5N1 may look a lot less scary. “Until we do that there's no way to know,” Racaniello said. “The bottom line is that it looks like a whole lot of people become infected and don't die,” says  Racaniello, who was not part of the study. “How much lower the death rate is, we don't know.”

Dr. Andrew Hayward, a flu expert at University College London, calls the new analysis an “important study.” The people “most likely to be tested for H5N1 are severe cases that end up in hospital,” Hayward said. “People who are ill enough to get tested for H5N1 have a very high risk of dying, but this work suggests that many more people in the community become infected” and do not die.

Michael Osterholm, director of the Center for Infectious Disease Research and Policy, which studies threats of bioterrorism, criticized the study. He said one of the studies included in the analysis looked at the 1997 bird-flu outbreak in Hong Kong, which, Osterholm said, raises the number of people who were seropositive. “The virus was a bit different,” he noted. In a press release from the American Society of Microbiology, Osterholm says the Hong Kong, the virus was H1N1, which is also influenza but genetically different from H5N1.

“Peter [Palese]'s paper just confuses the issue because of the Hong Kong experience,” Osterholm told LiveScience, adding that only more recent studies, of a virus  more similar to that plaguing humans today, should be used.

In fact, he said doing so would reveal that 0.5 percent of the participants were seropositive. He plans to publish a study in the journal mBio, February 24^th, showing that the virus might be even more deadly than the current mortality rate shows. Taking an average of the studies Palese used, Osterholm said, is therefore misleading. “If you put your head in the freezer and your feet in the oven, of course the average temperature will be just right,” he said.

“There are significant problems with the analysis,” said Arturo Casadevall, chairman of the department of microbiology and immunology at the Albert Einstein College of Medicine in New York and a member of the NSABB. Particularly worrisome, he said, is “the inclusion of several studies in the meta-analysis that may not have been appropriate,” speaking of the inclusion of the Hong Kong bird flu outbreak.

The National Science Advisory Board for Biosecurity, which last year called for deleting details of two studies, scheduled for publication in the journals Science and Nature, describing experiments aimed at making bird flu infectious among mammals. The experiments raised the prospect that if the mutated bird flu viruses escaped or could be reproduced, they could trigger a worldwide pandemic, which WHO experts estimated could kill more than 20 million people worldwide. A WHO summit that ended this week called for full publication of the two studies and for an extended halt to such research until stronger safety measures were assured in labs.