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Bird flu proving resistant to Tamiflu treatment

Two bird flu victims in Vietnam died after becoming resistant to the anti-viral drug Tamiflu, health experts have reported.
/ Source: news services

Signs that the H5N1 bird flu virus may be developing resistance to frontline drug Tamiflu in some patients are not necessarily a cause for alarm, a senior World Health Organization official said on Thursday.

Keiji Fukuda, a scientist at the WHO’s global influenza program, said some resistance was inevitable with any kind of drug.

“Whenever you use any kind of drugs, antivirals or antibiotics, you expect to see resistance develop in organs. Finding some resistance in and of itself is not surprising and is not necessarily alarming,” he told Reuters.

But findings published in the New England Journal of Medicine that four of eight patients treated in Vietnam for bird flu infections had died despite the use of Tamiflu indicated that more research was needed into how best to use the drug, Fukuda said.

“It just points out the need for more information ... What really is critical is understanding whether the way we are using the drugs contributes to that (resistance),” he added.

Fukuda said some resistance was inevitable with any kind of drug, and Tamiflu remained the best treatment.

“Whenever you use any kind of drugs, antivirals or antibiotics, you expect to see resistance develop in organs. Finding some resistance in and of itself is not surprising and is not necessarily alarming,” Fukuda said.

But more research was needed on optimal doses and length of treatment for people infected with the deadly virus, to limit the chances of resistance becoming more widespread, he added.

Other experts said the deaths were disturbing because the two girls had received early and aggressive treatment with Tamiflu and had gotten the recommended doses.

The new report suggests that the doses doctors now consider ideal may be too little. Previous reports of resistance involved people who had taken the drug in low doses; inadequate doses of medicine are known to promote resistance by allowing viruses or bacteria to mutate and make a resurgence.

Tran Tinh Hien, a member of the research group and deputy director of the Hospital for Tropical Disease in Ho Chi Minh City, told Reuters: “We still recommend the use of Tamiflu for bird flu cases as soon as possible and at higher doses as there is no replacement yet. More in-depth research is needed to determine the effectiveness of Tamiflu against the H5N1 virus.”

Hien said Vietnam’s Ministry of Health had increased the treatment period for Tamiflu to 7 days from 5 days previously. Most of the Tamiflu-treated patients who died had used the drug too late and their infection had become too severe, he added.

Using doses that are too small, or for too short a time, can contribute to resistance developing, according to Fukuda, who noted that the Vietnam study had been very small.

Concerns about Tamiflu resistance surfaced in October when doctors discovered it in a 14-year-old Vietnamese girl who had been given low doses as a precaution because she was caring for a brother with bird flu. She survived, and doctors theorized the low doses caused the resistance.

Risks of stockpiling
The new report involved eight Vietnamese bird flu patients given Tamiflu upon being hospitalized in 2004 or 2005. Half of the patients died. Lab tests showed two of those who died — girls ages 13 and 18 — had developed resistance.

In the case of the 13-year-old, doctors were especially surprised to see resistance because she was treated within the time frame when the drug was supposed to be most effective.

Dr. Anne Moscona, a flu expert at Weill Cornell Medical College in New York City, called the deaths frightening and said they demonstrate the dangers of hoarding drugs.

“People who stockpile will naturally share or take drugs at the wrong dose, and that’s really a bad idea,” said Moscona, who wrote an accompanying commentary in Thursday’s New England Journal of Medicine.

The study was led by Dr. Menno de Jong of Oxford University.

David Reddy, who heads Roche’s influenza pandemic task force, said the study merits further investigation into whether patients need more of the drug.

Tamiflu, made by Swiss firm Roche, remained an “excellent choice” among a limited number of antivirals available against the deadly virus, the WHO official said.

Since 2003, avian flu has killed about 70 people, mostly in Vietnam and Thailand, and nearly all involved close contact with infected birds. Health experts fear the virus could morph into a form that spreads easily between people.

Tamiflu and another drug, Relenza, are expected to be the front-line defense if that happens, but they must be taken soon after infection to be effective.

Death toll reaches 73
Roche is conducting animal studies of different dosages to see which works best. Results are expected early next year.

In addition, Roche is working with the World Health Organization and the National Institutes of Health to begin a human experiment next year that would test whether doubling the current recommended Tamiflu dose is more effective, Reddy said.

Bird flu has some health experts worrying about hoarding of Tamiflu, which is tight supply as countries scramble to stock up.

In October, Roche announced it was suspending shipments to U.S. wholesalers and other private-sector recipients to ensure enough Tamiflu for the regular flu season. Roche is also negotiating with other companies to increase production.

Two more human deaths from bird flu in Indonesia were confirmed on Thursday, taking the known global total to 73, while cases including survivors would rise to 141. All the deaths so far have been in Asia.

Experts fear the virus will mutate into one that can be passed from human to human, rather than from fowl to people, and that such a mutation might spark a pandemic killing millions.