Bird Flu Drug Rendered Useless

Two months before China first reported a bird flu outbreak in poultry to the World Animal Health Organization in February 2004, officials had begun a massive campaign to immunize poultry against the virus. They have now used at least 2.6 billion doses of a vaccine.

But researchers in Hong Kong have reported that the H5N1 flu virus has been circulating in mainland China for at least eight years and that Chinese farms suffered major outbreaks in 1997, 2001 and 2003. Scientists have traced the virus that has devastated farms across Southeast Asia in the last two years to a strain isolated from a goose in China's Guangdong province in 1996.

The U.N. Food and Agriculture Organization has long recommended that countries try to eradicate infectious animal diseases by slaughtering infected flocks and increasing safety measures on farms. Last year, the FAO also suggested that countries consider vaccinating their poultry against bird flu. But the guidelines never recommended the use of antiviral drugs such as amantadine, which, unlike vaccination, has been proven to make viruses resistant, officials said.

In 1987, researchers at a U.S. Department of Agriculture laboratory demonstrated that bird flu viruses developed drug resistance within a matter of days when infected chickens received amantadine.

Still, a veterinarian with personal knowledge of livestock practices across China said Chinese farmers responded to the bird flu outbreak by putting the drug into their chickens' drinking water. The veterinarian asked that his name not be published because he feared for his livelihood.

"This would explain why we're seeing such high resistance levels," said Michael T. Osterholm, director of the Center for Infectious Disease Research and Policy at the University of Minnesota. While various antibiotics have lost their effectiveness because of overuse, he said, the emergence of resistance to amantadine is unprecedented because it is an antiviral.

"This is the first example of an antiviral drug that was used for animal production that has major implications for human health," Osterholm said.

A popular Chinese handbook, titled Medicine Pamphlet for Animals and Poultry, provides farmers and livestock officials with specific prescriptions for amantadine use to treat chickens and ferrets with respiratory viruses. The manual, written by a professor at the People's Liberation Army Agriculture and Husbandry University and issued by a military-owned publishing company, prescribes 0.025 grams of amantadine for each kilogram of chicken body weight.

Farmers also use the drug to prevent healthy chickens from catching bird flu, giving it to their poultry about once a month or more often when the weather is liable to change and chickens are considered susceptible to illness, veterinary experts said. The antiviral is often mixed with Chinese herbs, vitamins and other medicine.

In the United States, amantadine was approved in 1976 by the Food and Drug Administration for treating influenza in adults. Amantadine and it sister drug, rimantadine, known collectively as amantadines, work by preventing a flu virus from reproducing itself. Both are now ineffective against the H5N1 strain.

International health experts stressed that amantadine could have been vital in stanching the spread of the bird flu virus in the early weeks of an epidemic.

Now, the only alternative is oseltamivir and closely related zanamivir, which stop the flu virus from leaving infected cells and attacking new ones. Oseltamivir is easier to use and has far greater sales.

"Amantadine is the cheapest drug against flu," said Malik Peiris, an influenza expert at the University of Hong Kong. "It is much more affordable for many countries of the region. Now, it is clearly no longer an option."

Special correspondents Ling Jin in Beijing and K.C. Ng in Hong Kong contributed to this report.