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Study of flu patients reveals virus outsmarting key drug

MADISON - A drug envisioned as a front-line defense for the next flu pandemic might have a genetic Achilles' heel that results in a drug-resistant influenza virus capable of infecting new human hosts, according to a study published this week (Aug. 28) in the British medical journal The Lancet.

The study of Japanese children with influenza and treated with the antiviral drug oseltamivir was conducted by an international team of researchers led by virologist Yoshihiro Kawaoka of the University of Wisconsin-Madison and the University of Tokyo. Results of the study showed that nearly 20 percent of patients treated with the drug produced mutant drug-resistant viruses as soon as four days after treatment. Moreover, patients continued to shed significant amounts of infectious viral particles even after five days of treatment with the potent antiviral agent.

"The problem with this compound is that a single (genetic) mutation makes the virus resistant," says Kawaoka, an authority on influenza who holds an appointment at the UW-Madison School of Veterinary Medicine.

The finding is important because it provides evidence that influenza viruses can easily and quickly thwart one of the few lines of defense for a disease that claims many lives each year and that, in a pandemic, is among the world's most feared and deadly diseases.

"The importance of this work is that when a pandemic occurs with a new virus and this drug is extensively used, then we may be faced with the rapid appearance of resistant viruses," Kawaoka says.

At present, there are only two strategies for stemming the spread of influenza: vaccines and antiviral drugs. Vaccines use inactivated forms of a virus to ramp up the immune system and thwart infection. Antiviral drugs such as oseltamivir work by inhibiting key proteins on the surface of the virus, effectively locking them in their host cells and preventing the virus from escaping and infecting new cells and hosts.


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Contact: Yoshihiro Kawaoka
kawaokay@svm.vetmed.wisc.edu
University of Wisconsin-Madison
26-Aug-2004


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