Influenza Virus Evades Key Drug

A small study of children with flu in Japan finds that the influenza virus can outwit a drug that was thought to be relatively foolproof. The paper, published in the 28 August issue of The Lancet, comes as some countries are stockpiling the same antiviral drug against a flu pandemic. Flu researchers say there's no need to stop stockpiling, however--the drugs should still prove useful.

The last major global influenza pandemic, the 1918 Spanish flu, killed 50 million people. Another big pandemic could be in the works if the highly virulent H5N1 avian flu, which killed at least 24 people in Asia last winter, assumes a form that can be transmitted from person to person. Because preparing a vaccine against such a virus could take 6 months, antiviral drugs would be the first line of defense against pandemic flu. Although the flu virus can develop resistance to some older drugs, newer drugs called neuraminidase inhibitors, which target an enzyme that makes a flu virus coat protein, have seemed more impervious. So some countries have begun stockpiling one of these drugs, oseltamivir (sold as Tamiflu).

The United States is among them, according to a federal pandemic flu plan released today. The United States has stored enough oseltamivir to treat 1 million people, officials said. The plan also describes steps to increase vaccine manufacturing capacity and how state and local health care providers should respond.

The Lancet report, however, suggests that flu virus develops resistance to oseltamivir more readily than was thought. Virologist Yoshihiro Kawaoka of the University of Tokyo and colleagues in Japan and the United States collected virus samples from 50 children taking a 5-day course of oseltamivir for a flu episode. In nine samples, or 18% of the children, the virus developed mutations that made it resistant to the drug.

But that doesn't mean antivirals won't work against a pandemic, says Kawaoka, who is also at the University of Wisconsin, Madison. For one, the changes that make a virus resistant to oseltamivir may make it less pathogenic, he says. In an accompanying editorial, Anne Moscona of Mount Sinai School of Medicine in New York City notes that another drug in this class, zanamivir, may be less prone to becoming resistant.

Moreover, adds flu expert Arnold Monto of the University of Michigan, Ann Arbor, avian flu strains won't necessarily become resistant to oseltamivir as easily. Monto, who serves on an international committee that recently recommended stockpiling neuraminidase inhibitors in the 13 August Weekly Epidemiological Record, concludes: "The message for most of us is, governments should stockpile."

Related Sites
Neuraminidase Inhibitor Susceptibility Network statement supporting antiviral stockpiling
U.S. Department of Health and Human Services Pandemic Influenza Response and Preparedness Plan