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Science & Technology
Tamiflu still best hope against bird flu, says WHO
2005-12-23
A senior World Health Organisation official yesterday sought to calm fears that the drug the world is stockpiling may have limited usefulness in a flu pandemic. Evidence that some people with bird flu in Vietnam rapidly developed resistance against the drug Tamiflu and died was not necessarily a cause for alarm, said Keiji Fukuda, an expert at the WHO's global influenza programme. More research was needed, however, on the use of the drug.
I'm not alarmed, but I am concerned.
His comments follow publication of a report in the New England Journal of Medicine on eight people with bird flu in Vietnam who were treated with Tamiflu. Four of them died. In two cases, the patients were very sick and although Tamiflu temporarily improved their condition, they died.
The other two cases have sounded warning bells around the world. Both had the usual strain of bird flu when they were admitted to hospital, but after some days of treatment with Tamiflu, the virus in their bloodstream mutated and became resistant to the drug.
Figure 1 in the article shows a series of chest x-rays in one patient over a period of 6 days. In that time, a localized pneumonia progressed to involve most of one lung despite Tamiflu treatment. For me as a pulmonary doc, it's a scary sequence.
The scientists, from the Oxford University Clinical Research Unit in Ho Chi Minh City, voiced concern that if a resistant strain of flu became easily transferable between humans - as bird flu is not at the moment - it could worsen any pandemic.

Yesterday, however, Dr Fukuda said that resistance was inevitable with any drug and Tamiflu was at the moment the best available treatment. "Whenever you use any kind of drugs, antivirals or antibiotics, you expect to see resistance develop in organs," he said. "Finding some resistance in and of itself is not surprising and is not necessarily alarming."

The study revealed the need for more information, he said. "What really is critical is understanding whether the way we are using the drugs contributes to that [resistance]," he said. Work needed to be done on the optimal dose of the drug against H5N1 (bird flu) and the length of the course of treatment.

The study's authors, Jeremy Farrar and colleagues, say that other antiviral drugs are needed alongside Tamiflu. The only other candidate, however, is Relenza, which has limited usefulness because it is administered as a nasal spray. It cannot be used by people who have trouble breathing, which occurs if it is severe flu. Its manufacturer, the British company GlaxoSmithKline, said it would be two years before they could produce an injectable form.
And we could end up with similar problems with resistance, though less likely with Relenza.
The deputy director of the Hospital for Tropical Diseases in Ho Chi Minh City, who was a member of the study group, said they were still using Tamiflu. "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," said Tran Tinh Hien. "More in-depth research is needed to determine the effectiveness of Tamiflu against the H5N1 virus."
An accompanying free article in the Journal describes how H5N1 becomes resistant, and the implications of mis-use of Tamiflu. Worth a look.
Posted by:Steve White

#3  Ah, yes, the ever-present "More research was needed..." Just don't give the funds to WHO if you want useful results.
Posted by: Darrell   2005-12-23 08:59  

#2  Roche mulls increasing Tamiflu dose to treat bird flu
Posted by: phil_b   2005-12-23 03:17  

#1  I have several problems with this article.

Firstly, the studies with 'normal' flu I have seen show Tamiflu be significantly less effective than people assume. In summary its highly effective, if taken before infection, Its moderately effective if taken around the time of infection and of limited effectiveness if taken after full symptom onset - when you are sick enough to go to a hospital. With H5N1 in mice it has only been show to be effective if administered prior to infection.

Secondly, the article presents no evidence that these 'resistance' mutations decrease the effectiveness of Tamiflu or by how much. The article assumes that Tamiflu's limited effectiveness results from the increasing prevalence of these mutations.

Further, the increasing incidence of certain mutations as a result of Tamiflu use doesn't necessarily mean these mutations confer complete or substantial resistance to Tamiflu. The mutations could result in only a slight decrease in effectiveness of the drug (as measured by the ability of the virus to replicate and perhaps no measurable cilinical difference). And I'd argue this is the likeliest scenario.

Finally, some people would argue that severe fatal flu such as found with H5N1 and in the 1918 pandemic results from a different mechanism (ARDS, Cytokine Storms) to the illness caused by 'normal' flu. The effectiveness of Tamiflu against this disease mechanism is unknown.
Posted by: phil_b   2005-12-23 01:22  

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