Another study has uncovered evidence that the H5N1 strain of avian influenza has developed resistance to Roche’s Tamiflu, exposing an urgent need for additional drug treatments for the infection.

Tamiflu lies at the heart of most national efforts to prepare for a flu pandemic, which the World Heath Organization fears could happen at any time. But a study in the New England Journal of Medicine reveals that two out of eight Vietnamese people treated with the drug after contracting H5N1 developed resistance to Tamiflu and died.

This occcurred the drug being administered to at least one of the two within the required time frame of 24 to 48 hours after infection with H5N1.

The authors suggest that higher doses of Tamiflu, longer durations of therapy or combination therapies may be needed for the treatment of patients infected with the H5N1 virus. But boosting the recommended dose of the drug would mean that stockpiles laid down by governments to treat a potential pandemic would not go so far, and Roche is already racing to boost manufacturing capacity for Tamiflu in the face of burgeoning demand.

In a statement, Roche pointed out that all patients infected with the current circulating strain of the H5N1 virus who received treatment with Tamiflu and survived had a rapid and consistent drop in viral load, backing up the effectiveness of the treatment. It agreed that resistance was a worry, but said evidence to date with seasonal flu suggests that it occurs only rarely. Meanwhile, the mutations in H5N1 that confer resistance are known to reduce the infectivity and transmission of the virus, it said.

The Swiss drugmaker also said it was collaborating with the US national Institutes of Health on a clinical trial exploring the role of higher doses of Tamiflu in the treatment of severe influenza, including H5N1.

The news follows an earlier report published on the website of the journal Nature (October 14) which described another patient in Vietnam in whom the virus had developed partial resistance to Tamiflu.

H5N1 has caused the death of millions of birds around thw world, but so far only 138 human cases of infection have been identified. But 71 of these have died. So far, no human to human transmission has been reported, but a mutation to allow this could spark a global influenza pandemic

Cleared for use in young children

Meanwhile, children as young as one in the USA can now receive Tamiflu to prevent exposure to influenza, after the US Food and Drug Administration approved new labeling for the drug.

The FDA says Tamiflu may now be used as prophylaxis for flu in children aged one through 12. The drug was previously approved for prevention in adolescents (age 13 years and older) and adults. Tamiflu was recommended for approval in Europe and Switzerland for prevention of influenza in children aged one to 12 years last week.

Extending the age range means that doctors can prescribe Tamiflu for younger children, who are particularly vulnerable during a flu outbreak, with more confidence, said William Burns, chief executive of Roche Pharma.

When administered within two days of close contact with an infected individual, clinical data show that prophylaxis with Tamiflu reduced the incidence of flu from 17% in the group not receiving Tamiflu to 3% in the group receiving prophylaxis.

Tamiflu is the only antiviral medication indicated for the treatment of influenza type A or type B infection in patients one year and older, and is available in both capsule and liquid suspension formulations.