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Avian Influenza Virus Exhibits Resistance to Amantadine and Rimantadine

New tests have turned up a disturbing problem with the avian influenza virus that is spreading in Asia: the strain appears resistant to one of the 2 main classes of drugs used to fight influenza viruses, a World Health Organization (WHO) official said yesterday [Sat 24 Jan 2004].

Meanwhile, avian influenza A(H5N1) virus has been detected among birds in a 6th Asian country, Cambodia, and 2 more human cases have been diagnosed in a new area of Vietnam, the official, Dr. Klaus Stoehr, said. Both Vietnamese cases were in children in Ho Chi Minh City, bringing to 7 the total in that country. 6 have been fatal. 5 earlier Vietnamese cases were in Hanoi. Thailand has reported 2 human cases. All the human cases are believed to be from contact with chickens or their waste, not from eating them or their eggs. The agency said it knows of no person-to-person spread of the disease.

The number of human cases is small, and the avian influenza A (H5N1) virus strain contains only avian genes. But WHO officials are concerned that the bird strain might exchange genes with a human virus to create an entirely new virus that could spread easily among people. It would take a combination of events, each of low probability, to produce a large outbreak. But the health agency said the implications for public health were so important that precautionary measures must be taken.

Because a virus [reassortment event] could occur at any time, and the threat is likely to last for some time, WHO is establishing systems for a long vigil through its influenza surveillance network, said Dick Thompson, a spokesman in Geneva. The organization, other United Nations agencies, and health groups are emphasizing that infected Asian countries must kill all poultry, a standard measure to stop avian influenza from becoming endemic.

Laboratories in the WHO network are using new techniques to try to develop a human vaccine. The agency hopes to develop in a month a seed virus for possible vaccine production. Dr. Nancy J. Cox, an influenza expert at the Centers for Disease Control and Prevention (CDC) in Atlanta, which is helping prepare a seed virus, said there was no guarantee on that time frame. “That would be the best-case scenario,” Dr. Cox said. Once the seed virus is ready, it will take months to produce a new vaccine and test it in animals and human volunteers.

Knowing that anti-influenza drugs may be needed in an outbreak of human bird flu, and as part of the surveillance process, laboratories in the network have been testing which of a small number of such drugs may be effective against the A (H5N1) strain. The tests are being done at the CDC in Atlanta, and in in London and Hong Kong.

Dr. Stoehr said on Friday night that his agency had learned that initial genetic tests showed that the A(H5N1) was resistant to the less expensive class of anti-influenza drugs. The class includes amantadine (Symmetrel) and rimantadine (Flumadiine).

Earlier studies by Dr. Malik Peiris of the University of Hong Kong showed that the resistance results from a single amino acid change. Additional tests are expected to be conducted this week to confirm the early findings, said Dr. Stohr. However, A(H5N1) is believed to be susceptible to the costlier class of anti-influenza drugs known as the neuraminidase inhibitors. Tamiflu (Oseltamivir) is the main drug in this class.

Before Cambodia was added to the list, A(H5N1) had been officially reported in birds from 5 countries: Hong Kong, Japan, South Korea, Thailand, and Vietnam. The WHO suspects that the virus is also present in other Asian countries.

Taiwan has reported that a different strain of avian influenza, A(H5N2), is causing mild illness among poultry. Tests show that the strain’s genes are closely related to those in a vaccine that is widely used for poultry in Hong Kong and China, Dr. Stoehr said. He said that one possibility was that the Taiwan bird cases were from a poor-quality vaccine.

[Byline: Lawrence K. Altman]