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Antiviral drug supresses deadly H5N1 avian flu
19/7/2005 10:52

An antiviral drug currently used against annual influenza strains has in mice experiments suppressed the deadly avian flu virus H5N1, US scientists reported on Monday.

This study, the first published one conducted on oseltamivir against the H5N1 influenza strain circulating in Vietnam, found that the drug commercially labeled as Tamiflu can dramatically boost the survival rate of infected mice. The researchers at St. Jude Children's Research Hospital have published the paper online in the Journal of Infectious Diseases.

The H5N1 virus strain, which spread from birds to humans, has killed dozens of people in Vietnam, Cambodia, Thailand, and Indonesia since early 2004. Public health experts fear that the avian flu virus could develop the ability to spread easily from person to person and kill millions in a deadly flu pandemic.

In this study, the research team gave one of three possible daily dosage levels of oseltamivir or a placebo to mice infected with H5N1 influenza virus. The highest dosage level, adjusted for weight, was equivalent to the dose currently recommended for humans sick with the flu.

Although the recommended human dose of oseltamivir is taken for five days, the researchers also tested an extended eight-day course in half of the mice. Oseltamivir decreases the ability of influenza virus to spread from infected cells to uninfected cells by inhibiting neuraminidase, which is an influenza protein required for the virus to exit infected cells.

Of 80 mice infected with H5N1 virus, 20 received a placebo, 30 were given oseltamivir at one of three dosage levels for five days, and 30 received the drug at one of three dosage levels for eight days.

None of the mice receiving a placebo survived, and only five of 10 mice given the highest daily dose of oseltamivir for five days survived. Although oseltamivir suppressed the virus in the mice, the virus continued to grow if the drug was stopped after five days, the researchers said.

But mice given the drug for eight days fared better. Survivors included one of 10 mice given the lowest daily dose, six of 10 given the middle-range daily dose, and eight of 10 given the highest daily dose. The eight-day dose of oseltamivir allowed more time for virus levels to fall and less chance for avian flu to rebound after the drug was stopped, explained the researchers.

In addition to testing the efficacy of oseltamivir against H5N1 virus in mice, the researchers compared the virulence of the new Vietnam virus with a 1997 variant of H5N1 that killed six people in Hong Kong, China.

They found that the 2004 H5N1 virus, currently circulating in Vietnam, is much more virulent than its 1997 predecessor. A longer course of antiviral treatment may be required to conquer the aggressiveness of the new antigenic variant of H5N1 virus, the researchers suggested.

"The H5N1 avian flu viruses are in a process of rapid evolution. We were surprised at the tenacity of this new variant," said lead investigator Elena Govorkova. "Our results provide baseline information that will be needed for further studies on preventing and treating avian flu with antiviral drugs."

The researchers said that further study is needed to see if using higher doses of oseltamivir for a longer period of time can prevent the H5N1 virus in the lungs from gaining a foothold and then spreading to the brain. They are planning additional studies in small animal models in which avian flu infection closely resembles the disease in human."

We need to know whether antiviral drugs can prevent and treat avian flu, because in the early stages of a global outbreak, most people would be unvaccinated," said Anthony Fauci, director of US National Institute of Allergy and Infectious Diseases (NIAID), "If a pandemic occurs, it will take months to manufacture and distribute a vaccine to all who need it."

 



 Xinhua news