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Antiviral Overuse Could Aid Deadly Flu

Resistance could build up over time

January 9, 2009

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U.S. health officials have been stockpiling Tamiflu, an antiviral drug, in the event of a deadly bird flu pandemic. But researchers say that strategy could have problems.

Researchers analyzed almost 700 genome sequences of avian influenza strains to document where and when the virus developed resistance to a class of antiviral drugs called adamantanes and how far resistant strains spread. The analysis suggests that heavy use of an antiviral drug can held the viruses build up a resistance to it.

To underscore their point, they use the example of Asia and Russia, where they say the use of cheap antiviral drugs has been of little help. The results should serve as a warning to those who consider Tamiflu the next great antiviral medication, the researchers say.

Stockpiling Tamiflu has become a standard part of many government, business and health organization plans to prepare for a long-feared pandemic flu outbreak, especially in the event that avian flu mutates enough to infect and be easily transmitted among humans.

"We can't necessarily say what we've seen in adamantanes is predictive of what will happen with Tamiflu. But in the larger dynamic, perhaps it serves as a cautionary tale," said Daniel Janies, senior author of the study and an associate professor of biomedical informatics at Ohio State University. "Fighting infection is an arms race, and if we're not smart about how we use our arms and understand the evolutionary implications, then we will have ongoing and accelerating problems with drug-resistant microorganisms."

Resistance to adamantanes among strains of seasonal influenza spiked in Asia in 2002, and by 2006 the agents were considered virtually worthless worldwide as a treatment for the flu because more than 90 percent of the strains had developed a resistance to the drugs.

With that knowledge, Janies and colleagues analyzed hundreds of avian flu genomes isolated from avian, feline and human hosts between 1996 and 2007. They found that about one-third of those samples carried mutations enabling the virus strains to resist the effects of adamantane drugs.

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