Experiments in mice show that an antiviral drug currently used against annual influenza strains also can suppress the deadly influenza virus that has spread from birds to humans, killing dozens of people in Vietnam, Cambodia and Thailand since early 2004. This study, the first published report conducted on oseltamivir against the H5N1 influenza strain circulating in Vietnam, found that the drug, sold commercially as Tamiflu, dramatically boosted the survival rate of infected mice.
The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), funded this research at St. Jude Children?s Research Hospital in Memphis, TN. Results of the study are now available online in the Journal of Infectious Diseases.
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 its study, the St. Jude 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. 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.
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.
In addition to testing the efficacy of oseltamivir against H5N1 virus in mice, the St. Jude researchers compared the virulence of the new Vietnam virus with a 1997 variant of H5N1 that killed six people in Hong Kong. Researchers found that the 2004 H5N1virus, 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 suggest.