Study suggests older antivirals could help fight H5N1

May 12, 2006 (CIDRAP News) – An analysis of more than 600 H5N1 avian influenza viruses collected from several Asian countries suggests that two older antiviral drugs could be more useful in fighting a flu pandemic triggered by H5N1 than previously believed.

Most H5N1 viruses collected from humans and poultry in Vietnam and Thailand have been resistant to the two older drugs, amantadine and rimantadine (known as the adamantanes). As a result, hopes for an effective drug have focused on the newer antivirals, oseltamivir and zanamavir. Many countries have been stockpiling oseltamivir.

But an international team of scientists is reporting that resistance to amantadine seems less common than has been believed, at least in some countries. As expected, they found that most viruses from Vietnam, Thailand, and Cambodia had mutations that signaled resistance to amantadine. But only a few of the viruses from China and Indonesia had those mutations.

"Amantadine appears to retain the potential to be useful in an H5N1 pandemic in the absence of a vaccine, as a prophylactic agent and as a component of combination antiviral therapy," says the report, published online by the Journal of Infectious Diseases.

The study was done by scientists from the University of Hong Kong; Shantou University in Guangdong, China; St. Jude Children's Research Hospital in Memphis, Tenn.; and the Center for Indonesian Veterinary Studies in Jakarta. Chung Lam-Cheung of the University of Hong Kong was the first author.

The researchers analyzed the genetic sequences of the M2 ion channel protein of 638 H5N1 viruses, including 599 from birds and 39 from humans. Most of the isolates came from Hong Kong, China, Vietnam, Thailand, and Indonesia, with a few from Cambodia, Malaysia, Japan, and Korea. The sequences were screened for four mutations predicted to confer amantadine resistance.

Tabular data in the report show that 92.6% (162 of 175) of the Vietnam isolates had resistance mutations, as did all the isolates from Thailand (58 of 58), Cambodia (9 of 9), and Malaysia (2 of 2). In contrast, only 13% (16 of 123) of the isolates from China and 6.3% (2 of 32) of those from Indonesia had such mutations. None of the eight isolates from Japan and Korea, collected from poultry in late 2003, showed resistance.

"Although amantadine-resistant H5N1 viruses are present in Asia, their distribution appears to be largely limited to Thailand, Vietnam, and Cambodia," the report states. In an apparent reference to reports of amantadine use in poultry in China, the authors add, "That most H5N1 isolates from China and Indonesia are sensitive to amantadine is striking and perhaps surprising, in view of the reportedly widespread administration of amantadine to farmed poultry in some countries."

Amantadine and rimantadine have been used in treating human flu for more than a decade. However, flu viruses can quickly become resistant to the drugs, because just one point mutation is required. Last January, the Centers for Disease Control and Prevention advised physicians to stop prescribing the drugs for the rest of the flu season because the predominant strain of influenza A had turned highly resistant to them. The resistance rate in the H3N2 strain had soared to 91%, compared with 11% the year before.

Cheung C-L, Rayner JM, Smith GJD, et al. Distributionof  amantadine-resistantH5N1avianinfluenzavariants in Asia. J Infect Dis 2006 Jun 15;193(12):1626-9 [Full text]

See also:

CIDRAP information on the use of antiviral drugs in a flu pandemic

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