January 6, 2006

Scientists in Uphill Battle to Fight Bird Flu

By Tan Ee Lyn

HONG KONG -- Fighting the deadly H5N1 bird flu virus is all the more difficult because experts are still figuring out how best to use Tamiflu, believed to be one of the very few defenses, scientists said.

Roche AG's Tamiflu, generically called oseltamivir, is an anti-viral designed to fight human influenza. But tests have suggested it may be effective in reducing the severity of H5N1 and its complications if taken in higher doses.

Still, scientists have only just begun experimenting how best to use the drug in fighting the H5N1, which health experts fear will mutate into a form that is easily transmissible among people and unleash a pandemic, killing millions.

"The truth of the matter is, we don't really know what is the correct dose, or how many days do you have to treat with Tamiflu and what is the dose required," said virologist Robert Webster of the St. Jude's Children's Hospital in Memphis, Tennessee.

"There is still space for research to be done ... on how many days to treat, what dose to use. The standard tablets may not contain enough drugs. Maybe it requires more because all of these things were determined for standard human flu."

Three children from the same family in Turkey have died of bird flu over the past week. They were the first human fatalities outside China and East Asia since 1997, when the H5N1 virus made its first known jump to humans in Hong Kong.

The disease has re-emerged in China and Southeast Asia since 2003, killing 74 people. Like the East Asian victims, the Turkish children are known to have lived in close proximity with poultry.

A recent article in the New England Journal of Medicine reported how four of eight patients in Vietnam died despite using Tamiflu. It sparked concern as it suggested that certain strains of the H5N1 might have become resistant to the drug.

It also showed that experts were just figuring out how best to use the drug.

In one patient, Tamiflu was used early on, as is recommended by experts and the drug maker -- but Webster, speaking in Hong Kong, said these guidelines were meant to fight human flu viruses, not bird flu viruses.

"These patients in Vietnam ... certainly received the dose that was recommended on the package, but those studies were done with standard H3N2, H1N1 (human flu) viruses," said Webster, who is trying to find out if the best way to fight H5N1 is through the use of a cocktail of drugs, including Tamiflu.

"We are still learning how best to use this drug. The studies from Vietnam tell us you have to think about early treatment. With late treatment, you will have a problem with resistance."

William Chui, a pharmacologist based in Hong Kong, agrees: "The speculation in the Vietnam cases is that the recommended dosage was not high enough. Whether it's dosage, duration of treatment, they are all trial and error (for H5N1)."

Webster said Tamiflu could only be of use against H5N1 if it is taken within one to 1.5 days of infection -- and not within 48 hours of the patient showing symptoms as advised by many experts.

"The issue is when was the drug started in patients after they got infected. Published work on the use of Tamiflu shows it is only effective for the first day. You must begin treatment in the first day or maximally 1.5 days after initial infection. Not symptoms, that is the difficulty," Webster said.

Apart from Tamiflu, experts believe GlazoSmithKline's Relenza, another anti-viral drug known generically as zanamivir, may work against the H5N1.

There is an experimental H5N1 human vaccine but it is based on the current H5N1 strain and experts have warned that it may just not match a future pandemic strain.