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

“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),” Keiji Fukuda, an expert at the WHO’s global influenza programme, told Reuters.

Two more human deaths from bird flu in Indonesia were confirmed on Thursday, taking the known global total to 73, all in Asia.

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

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.

Findings published in the New England Journal of Medicine showed that four of eight patients treated in Vietnam for bird flu infections had died despite the use of Tamiflu.

According to the study, tests showed that in two of the patients, the virus had developed resistance to Tamiflu, which is made by Swiss drugs firm Roche. For the other two, treatment may simply have started too late.

Roche shares were down 0.96 percent at 1315 GMT.

TOO SMALL DOSES

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.

“We have to monitor the situation to see whether resistance becomes a big problem or not,” Fukuda said.

Tamiflu, in a class of drugs known as neuraminidase inhibitors, remained an “excellent choice” among a limited number of antivirals available, he said.

GlaxoSmithKline and Biota’s Relenza, known generically as zanamivir, is an alternative to Tamiflu and has been shown to be active against Tamiflu-resistant virus.

But Relenza must be inhaled, making it problematic for patients with respiratory conditions such as asthma.

Glaxo hopes eventually to develop an injectable form of the medicine to overcome this limitation, but a spokeswoman in London said it was unlikely to be ready for at least two years.