Bird flu strain develops resistance to drug stockpiled by Britain

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The only drug available against a threatened pandemic of avian flu may be useless for many of those infected and could make the pandemic worse, scientists fear.

The warning came after a study of 13 Vietnamese patients infected with avian flu (H5N1) who were treated with the anti-viral drug, Tamiflu, found two developed a resistant virus strain which contributed to their deaths. In all, seven of the 13 patients died. The New England Journal of Medicine, which publishes the findings today, describes them as frightening.

Governments around the world, including the UK, are stockpiling Tamiflu to be used as the first line of defence against a flu pandemic.

But indiscriminate use of the drug in the event of a pandemic could fuel the growth of a resistant virus strain, triggering a second wave of infection against which there would be no defence, researchers say. Yesterday, Sir John Skehel, director of the National Institute for Medical Research in London, and one of the world's leading virologists, said: "The fear is that all the virus that comes here might be resistant."

Sir John said Tamiflu was better at preventing infection with flu than treating it. "It's a prophylactic not a therapeutic."

He urged the Government to broaden the UK's defence. Relenza, an inhaled drug which works in a similar way to Tamiflu, has not shown signs of triggering resistance but it has been ignored because it is harder to take. "We should be stockpiling other drugs. Some of these mutations are only resistant to Tamiflu. But I am not aware how much Relenza is available," Sir John said.

The H5N1 virus has infected 138 people in the Far East and killed 71 but the fear is it could mutate to become transmissible among humans.

In the Vietnamese study, one of the patients, a 13-year-old girl whose mother had died of avian flu, was treated with a high dose of Tamiflu within 24 hours of developing a cough and fever, when "the greatest clinical benefit could have been expected". But although her condition improved at first, it later worsened and she died eight days after starting treatment. A resistant virus strain was isolated and at the time of her death the amount of virus in her throat had increased.

The second patient died after 14 days, also showing signs of an increase in the amount of virus.

The two cases follow an earlier report of partial resistance in a Vietnamese patient infected with avian flu last February, who was given preventive treatment with the drug at a lower dose. In that case, the patient survived.

Professor Anne Moscona of Cornell University says in the journal that the Vietnamese cases "raise the worrisome prospect that even with therapeutic doses", resistance to Tamiflu may emerge.

Dosages may need to be raised and treatments combining several different drugs used, Professor Moscona says. Personal stockpiling of Tamiflu could lead to sharing of drugs, leading to under-dosing of infections, which could in turn fuel the pandemic.

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