A strain of H5N1 bird flu virus found in an infected Vietnamese girl is resistant to the drug being stockpiled by more than a dozen countries, including the United States, as a defense against a possible global pandemic, researchers reported yesterday.
The new finding, while not unexpected, raises the possibility that oseltamivir, sold as Tamiflu, might be less useful than anticipated if resistant strains of the H5N1 avian flu virus become more prevalent and the virus gains the ability to pass easily from person to person -- a trait it does not possess now.
Yesterday's report is the first indication that tests have detected a drug-resistant strain of H5N1 since the virus began circulating among birds in Asia. It was found in a 14-year-old Vietnamese girl who became ill in February while caring for her brother, who was also infected. She had initially received a low preventive dose of Tamiflu, and then a higher dose when she became ill. She recovered fully.
The report, by Q. Mai Le of Vietnam's National Institute of Hygiene and Epidemiology, in Hanoi, and 15 international collaborators, will appear in next week's issue of Nature. The journal released it early "owing to its relevance to current public debates," a spokeswoman said.
Tamiflu is in a class of antiviral drugs called neuraminidase inhibitors. Although resistant to Tamiflu, the strain reported yesterday remained susceptible to another member of the class, zanamivir, sold as Relenza. All H5N1 viruses are resistant to the other main class of flu drugs, adamantanes, which include amantidine and rimantidine.
The H5N1 strain has infected 117 people in Southeast Asia and killed 60 since December 2003. It has also killed, or led to the culling of, 140 million domestic birds.
Genetic fingerprinting of the resistant strain suggests that the girl was infected by her brother, as their viruses were extremely similar. But it appears that the resistance developed in the girl.
Drug-resistance mutations in viruses are rare and arise by chance. When they occur in the presence of a drug, however, a resistant strain can become dominant through natural selection as susceptible strains are killed off. The girl harbored three strains -- one resistant to oseltamivir, one partially resistant and one susceptible. All three were probably descended from the single strain that initially infected her.
Tamiflu resistance has appeared in other strains of the influenza A virus, the broad family that includes H5N1. Japanese researchers reported last year that in a small group of children treated with Tamiflu, 18 percent developed resistant viruses.
A major unanswered question is whether a Tamiflu-resistant virus can pass from person to person. No such cases have been reported for any strain of influenza A.
"People shouldn't think that Tamiflu is not going to work. Tamiflu is going to work," said Anne Moscona, an infectious-diseases specialist at Weill Medical College of Cornell University, who wrote a review of the drugs in the New England Journal of Medicine last month. "We have reason to hope that resistant strains will not be transmissible and will not be the ones spreading in a pandemic."
The U.S. Strategic National Stockpile of drugs contains 2.3 million treatment courses of Tamiflu, with more on order, but only 83,000 courses of zanamivir (Relenza).
After confirmation that the H5N1 bird flu virus had reached Turkey and may be in Romania, the European Union yesterday announced new measures to combat its spread, telling governments to pinpoint the areas most at risk and to separate poultry from wild birds, which carry the virus. News services reported that the commission acted on the advice of health and veterinary experts who held an emergency meeting.
Europe's poultry industry is bracing for heavy losses should bird flu take hold, hitting export markets and dampening consumer demand.
The World Health Organization said the spread of the virus to Europe's fringes has increased the chances of human cases. And Health and Human Services Secretary Mike Leavitt, on a visit to bird flu-afflicted countries in Southeast Asia, said that the spread of the disease is a "troubling sign" and that the world must work harder to prepare for a flu pandemic among people.