China’s Ministry of Agriculture has denied accusations that it approved the use of the human antiviral drug amantadine as a preventive measure against avian influenza in poultry. Its widespread use by Chinese farmers is now being blamed for producing strains of avian flu that are resistant to the drug. A report by the Washington Post (18 June, p A01) said that Chinese farmers had been using amantadine since the late 1990s and that it was a practice that was encouraged by government officials.
The Ministry of Agriculture, however, has said that the allegations are untrue. "We have never approved or permitted farmers to use amantadine to treat avian flu or other animal and viral diseases. Since 2004 we have approved three kinds of highly effective vaccines that can completely meet the need for avian flu control," the ministry’s statement said.
"The Ministry of Agriculture has told us that they never approved the use of amantadine in poultry and that they are fully aware of the consequences [of using it], but it seems that some farmers have misused the drugs," said Noureddin Mona, the United Nations Food and Agriculture Organization’s representative to China, Mongolia, and North Korea.
The Washington Post story reported officials of the Chinese pharmaceutical industry as saying that the Ministry of Agriculture had approved the production and sale of the drug for use in chickens. "Amantadine is widely used in the entire country. Many pharmaceutical factories around China produce amantadine and farmers can easily buy it in veterinary medicine stores," Zhang Libin, head of the veterinary medicine division of the Northeast General Pharmaceutical Factory in Shenyang, was reported as saying.
The report also cited a popular manual written by a professor at the People’s Liberation Army Agriculture and Husbandry University, Medicine for Animals and Poultry , which gives specific prescriptions of amantadine for treatment of respiratory infections in chickens.
The widespread use of amantadine helps to explain why scientists have seen growing resistance to the drug. Resistance by the H5N1 virus to amantadine was detected in Vietnam, Thailand, and Hong Kong, and was noted in research published in 2004 (Proceedings of the National Academy of Sciences 2004;101:8156-61 and Nature 2004;430:209-13).
The World Health Organization has seen growing resistance to the drug too. "WHO and other agencies have known for a while that it can lose its efficacy in as little as 72 hours in normal flu cases. Recent studies by WHO reference laboratories indicate that while amantadine resistance has been increasing steadily, in China it is well above the current average," said Roy Wadia, WHO’s spokesman in China.
"The drug has been legally available over the counter for human use for the last two years, and its use in poultry may have contributed to the overall situation. If it has that would hasten the curve of resistance and would be disappointing because it would render the drug practically useless. It may still be useful for seasonal flu in other parts of the world but likely not in this part," he said.
The H5N1 virus is now resistant to both amantadine and its sister drug rimantadine. The remaining treatments are oseltamivir and zanamivir. The prohibitively high cost of these two drugs should prevent their use in poultry, said Mr Wadia, adding that they are not for sale over the counter drug either.