Avian Flu Shows Resistance to Tamiflu

Experts say finding may be cause for concern in face of potential flu pandemic

FRIDAY, Oct. 14, 2005 (HealthDay News) -- Many public health experts have pinned their hopes on the antiviral drug Tamiflu to help stem a potential pandemic caused by avian flu, but a new report reveals the virus can become resistant to Tamiflu in some patients.

According to the article, which appears in the Oct. 14 online issue of Nature, a strain of the H5N1 flu virus that infected a Vietnamese girl in February is resistant to Tamiflu (oseltamivir).

Although the girl recovered, the finding raises concerns that Tamiflu may not be enough to fight a potential H5N1 pandemic. The girl could have been infected by her brother rather than by birds, according to study author Yoshihiro Kawaoka, from the University of Wisconsin. However, this needs further investigation before it can be verified, the authors noted.

While the strain of the virus was resistant to Tamiflu, when the research team tested the virus in ferrets they found that it was still sensitive to another antiviral drug -- Relenza (zanamivir).

Given that, "it could be useful to stockpile zanamivir, as well as oseltamivir, in the event of an H5N1 influenza pandemic," the authors concluded.

One expert said this mutation of the virus was not unexpected, and warned against the overuse of Tamiflu.

"This isn't terribly surprising," said Dr. Arnold S. Monto, a professor of epidemiology at the University of Michigan School of Public Health. "We know that you can get a mutation in a small number of people who are treated."

The question is what that means for the virus's ability to spread, Monto noted. "In our experiments with ferrets, the mutated virus seems a little bit less infectious than the wild type, which gives you some hope that it will not be that easy to transmit," he said.

Monto added that, while this mutated strain is susceptible to Relenza, there is no guarantee that Relenza will be effective against the avian flu, because Relenza is not designed to treat a systemic infection such as the avian flu.

"If, when the virus transfers from humans to humans, it stops being a systemic infection, then Relenza might be a realistic option," he said. "If it does not and we see an increased resistance to oseltamivir, then we've got a problem on our hands."

Given the potential resistance to Tamiflu, Monto said, "We need something else to use for a systemic infection." In addition, "we have to be careful that we don't abuse oseltamivir, because that's a sure way to bring out any tendency for selection of a resistant strain."

Right now the drug is in limited supply, so the chance of its overuse is small. However, an Indian pharmaceutical company, Cipla Ltd., announced plans to market a generic version of the Tamiflu early next year, the Associated Press reported Friday.

Roche Holding AG, which makes Tamiflu, has refused to license generic versions of the drug, despite pressure from several countries and United Nations Secretary General Kofi Annan, according to the AP.

Cipla told the wire service it would only sell the generic in developing nations, but a Roche spokesman said the company would protect its patent rights if it felt those rights were being infringed.

Roche also just announced it's increasing Tamiflu production to create stockpiles of the drug, but it said governments may have long waits for their orders to be filled.

Despite the potential resistance problem, Monto believes that countries still need to stockpile Tamiflu.

"We know in most cases the virus is susceptible," he said. However, Monto noted that larger doses given over a long period might be needed, particularly if the avian flu remains a systemic infection in humans.

More information

The U.S. Centers for Disease Control and Prevention can tell you more about avian flu.

SOURCES: Arnold S. Monto, M.D., professor of epidemiology, University of Michigan School of Public Health, Ann Arbor; Oct. 14, 2004, Nature online; Associated Press
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