The H5N1 avian influenza strain developed strong resistance to oseltamivir, better known as Tamiflu, in two Vietnamese patients who died from the virus early this year, according to a new study. Although not unexpected, the findings offer more evidence that the drug, currently being stockpiled by countries around the world, is likely to be useless in some patients should a bird flu pandemic occur. Researchers say countries should do what they can to minimize that risk--for instance by discouraging people from hoarding the drug.
Oseltamivir has only been on the market for 5 years, and researchers are anxiously monitoring the emergence of resistance to it. Seasonal flu strains such as H1N1 and H3N2 have shown little resistance to the drug in adults, but two small studies have shown resistance rates of up to 18% in Japanese children (ScienceNOW, 26 August 2004).
There's little experience with oseltamivir against H5N1, however. Partly that's because there have been fewer than 140 known patients so far. In October, researchers reported the first known case of partial oseltamivir resistance in a 14-year-old Vietnamese girl infected with H5N1. The virus was isolated while she took a low-dose prophylactic course, however, which may have helped the virus become resistant.
Now, researchers in Vietnam show that resistance can arise even in people who receive a standard treatment course of oseltamivir. They describe virus strains with mutations known to confer high resistance to oseltamivir, which they isolated from a 13-year old girl and a 35-year old woman killed by H5N1. The strains in six other patients on oseltamivir did not develop resistance. Because these patients recovered, the researchers suggest that resistant strains can be more dangerous. The research is reported in this week's New England of Medicine by Menno de Jong from the Oxford University Clinical Research Unit, based at the Hospital for Tropical Diseases in Ho Chi Minh City, and colleagues.
The "frightening report" not only shows that other types of flu drugs are needed, but also that oseltamivir should be used wisely to avoid resistance, writes Anne Moscone, a pediatrician at Cornell University in Ithaca, New York, in an accompanying editorial. People should be "strongly discouraged" from buying personal stockpiles, because these may be shared or otherwise used improperly, eliciting resistance, she says.
Fortunately, studies so far have shown that oseltamivir-resistant strains don't replicate very well, says epidemiologist Arnold Monto, an expert in flu drugs at the University of Michigan in Ann Arbor. That means that although the drug may not help individual patients, they are unlikely to spread the resistant virus, he says.