Bird Flu Pandemic May Not Develop

Virus doesn't show signs of mutating easily, U.S. government researchers now say

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By Amanda Gardner
HealthDay Reporter

MONDAY, July 31, 2006 (HealthDay News) -- A bird flu pandemic might not be imminent, as many health experts have feared, U.S. researchers now say.

When government researchers tried to combine the deadly H5N1 strain of bird flu with a common strain of flu that infects humans, they were unable to produce a strain that could be transmitted easily.

Health officials across the globe have worried that the bird flu virus that has killed 134 people worldwide might mutate, possibly in tandem with a more common flu virus, unleashing a new type of flu virus that could prove even more deadly because people's immune systems would not be able to fend off the disease.

The U.S. research, conducted with ferrets, offers some hope that a bird flu pandemic may not strike in the foreseeable future, if at all. But, the scientists cautioned, the genetics of flu viruses are unpredictable, and this study was based on one combination of viruses, when more than 50 possible combinations exist.

"Simple combinations of genes from both parent viruses have not led to enhanced transmissibility in the ferret," Dr. Julie Gerberding, director of the U.S. Centers for Disease Control and Prevention, said at a press briefing Friday. "These data do not mean that H5N1 cannot develop into a pandemic strain. It means that the genetics of that transformation are more complicated than a simple one-to-one exchange. We are far from out of the woods on a global scale," she added.

While the finding doesn't mean the previous alarm has been much ado about nothing, it may have been "much ado about theory, about something speculative," said Dr. Marc Siegel, author of Bird Flu: Everything You Need to Know About the Next Pandemic, and a clinical associate professor of medicine at New York University School of Medicine.

"This does add emphasis to my previous analyses that multiple steps may be necessary before this particular bird flu can become a pandemic strain, and we would be wise to not take those steps for granted," Siegel said. "This doesn't prove that H5N1 can't be the pandemic virus either, but it shows that there seem to be several steps involved."

The new research also casts some doubt on how much of a breakthrough drug maker GlaxoSmithKline's new bird flu vaccine really is, Siegel added. "That vaccine is a major triumph if H5N1 is the next pandemic strain," he said. "But we'd be better to go to a more modern method where you don't have to know what the strain is. We wouldn't be stockpiling against something that looks like it's several steps away from being the pandemic."

The new findings are published in this week's issue of the Proceedings of the National Academy of Sciences.

The existing H5N1 bird flu strain has generated more fear than normal because of its virulence and ease of transmission among flocks of domestic birds. So far, bird flu has infected 231 people around the world and killed 134.

Human casualties remain largely confined to Asia and to people who have had close and prolonged contact with infected birds, such as poultry farm workers. Worries about bird flu have also led to the destruction of tens of millions of poultry, mostly in Asian nations, as officials struggle to contain the virus.

Three conditions are necessary for a pandemic to occur, Gerberding said: It must be a new virus for which humans lack antibodies; it must be a virus that can cause infection and disease; and it must be a virus that moves easily from one person to another.

The first two conditions have been met with the current H5N1 avian flu virus, but not the third.

A flu virus could acquire the ability to jump easily from person to person in one of two ways. First, genetic changes could take place over time that would make the virus progressively more transmissible, which is likely what happened during the 1918-1919 flu pandemic that killed between 20 million and 40 million people worldwide. Or the change could happen more suddenly, when one virus exchanges genetic material with another virus that's already circulating easily among humans. This is probably what happened with the 1957 and 1968 pandemics, Gerberding said.

"We assessed the more sudden approach," said the CDC's Jacqueline Katz, a co-author of the study. "The research was undertaken to better understand what changes are needed for H5N1 to acquire the properties of efficient transmissibility."

Katz and her colleagues used a 1997 version of the H5N1 bird flu virus and the H3N2 human virus that circulates each year. Ferrets were used for the study because viruses transmit the same way in these animals as they do in humans.

Because the researchers were trying to generate a virus that had the properties of a pandemic strain, all experiments were done under the highest possible level of security, Bio Safety Level 3.

Using a process called reverse genetics, the researchers mixed the eight genes of the H5N1 virus with the eight genes of the H3N2 virus. When the resulting viruses were tested in ferrets, they weren't able to transmit efficiently or cause severe disease. This remained the case even after the viruses were retransmitted five times from one healthy ferret to another one. In other words, the retransmissions didn't allow additional mutations to occur that would be necessary for a pandemic.

"The most important thing is the knowledge that this process isn't simple, and it's a complex procedure for a virus to acquire the properties of transmissibility," Katz said.

There are, in fact, more than 50 virus combinations out there.

"We chose to use some that had what we believed the greatest likelihood of being a good virus that grew well and was viable and therefore had the potential for transmission. But there are many other combinations that we could investigate in the future," Katz said.

Also, there are new versions of H5N1 and H3N2 that need to be tested.

The good news is that the ferret model used for this study as well as a guinea pig model currently under development are viable research tools.

"Overall, this work tells us we have a good research tool to assess the ongoing genetic changes that H5N1 viruses may acquire and that may enhance the ability to transmit efficiently," Katz said. "We need to continue these studies, and the first study has shown that we now have a good model for continued assessment of more recent strains for their ability to re-assort with human strains, and that is work that is ongoing at the moment."

But we're still far short of being out of the woods, Gerberding warned.

"The flu is always unpredictable," she said. "We've got strains emerging probably as we speak. Let's not use the word 'reassuring' in terms of what might happen with H5N1."

More information

Visit the U.S. Centers for Disease Control and Prevention for more on bird flu.

SOURCES: July 28, 2006, press conference with Julie Gerberding, M.D., director, U.S. Centers for Disease Control and Prevention, and Jacqueline Katz, Ph.D., U.S. Centers for Disease Control and Prevention, Atlanta; Marc Siegel, M.D., author, Bird Flu: Everything You Need to Know About the Next Pandemic, and clinical associate professor, medicine, New York University School of Medicine, New York City; July 31-Aug. 4, 2006, Proceedings of the National Academy of Sciences

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