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Avian-Flu Study Reveals Hurdles for a Pandemic

http://online.wsj.com/article/SB115437280078622511.html

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By BETSY MCKAY
August 1, 2006

A new study from the Centers for Disease Control and Prevention suggests that it might be more difficult for the deadly avian-flu virus to spark a pandemic than originally feared.

In research published in the latest issue of the journal Proceedings of the National Academy of Sciences, CDC scientists reported that a simulation of one of two main paths the H5N1 virus could take to adapt itself to humans -- mixing genes with a common human-flu virus -- didn't create a lethal superbug that could jump from one human to another. But they cautioned that the avian flu virus could still evolve into a pandemic bug in other ways.

The findings are the result of experiments conducted in a high-security laboratory at the CDC's Atlanta headquarters to mimic the formation of a pandemic bug that many experts fear could occur in nature if an H5N1 avian virus infects a person who also has been sickened with a strain of common flu. The two most recent human-flu pandemics, in 1957 and 1968, were caused by such hybrid viruses, the CDC says.

After painstakingly swapping the genes of an early strain of the H5N1 virus with the genes of a common H3N2 virus that causes seasonal flu, the CDC researchers found that none of the new hybrid viruses transmitted easily when tested on ferrets. Ferrets transmit the flu and experience symptoms in a way similar to humans.

But the findings don't mean that the deadly H5N1 virus, which has ravaged poultry flocks across Asia, Europe, and Africa and killed at least 134 people since 2003, doesn't pose a pandemic threat, CDC Director Julie Gerberding warned. "These data do not mean that H5N1 cannot convert to become transmissible," she said. Instead, they indicate "that it is probably not a simple process."

A hybrid, or reassortant, virus could form by a more complicated process than an obvious one-to-one exchange of genes, Dr. Gerberding said. The H5N1 virus also could undergo genetic mutations on its own, as researchers say an avian-flu virus did to create the 1918 pandemic that killed millions of people. Some of the mutations the 1918 virus underwent have been detected in the current avian-flu virus, researchers on that virus have said.

The CDC also conducted its experiments on a 1997 strain of the H5N1 virus, and newer, more pathogenic strains now circulating could produce different results, CDC scientists and others caution. The H5N1 virus has undergone a significant number of mutations since 1997 -- enough so that vaccines developed to protect against earlier strains offer little protection against current strains. "The virus has clearly changed substantially between 1997 and 2006," said Michael Osterholm, director of the Center for Infectious Disease Research and Policy at the University of Minnesota, citing the virus's continued geographic spread and its penchant for infecting a growing number of mammals besides birds.

Jacqueline Katz, an author of the CDC paper, said the agency is conducting more experiments with more recent strains of the H5N1 and H3N2 viruses. Tests already conducted on 2003 and 2005 H5N1 viruses show that they were transmitted in a similar way to the 1997 virus, but their ability to mix with other viruses hasn't yet been determined.

…The CDC's work involved developing a new model for testing the transmissibility of viruses, which Dr. Katz and others said will help speed research on the threat posed by new flu strains as they emerge.

"You have a tool to really heighten the level of surveillance," said Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, a part of the National Institutes of Health. "As viruses now crop up, you can use this model."
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