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Resistance to Tamiflu Found in Bird Flu Virus

Mutation in H5N1 virus confers resistance to antiviral drug

October 17, 2005

Resistance to the most widely used antiviral drug, Tamiflu, appeared in the avian flu virus isolated from one patient, reports Yoshihiro Kawaoka, a virologist at the University of Wisconsin, Madison, and at the Institute of Medical Science at the University of Tokyo, and her colleagues (Nature, published online Oct. 14,

Tamiflu, with the active ingredient oseltamivir, is now being used to prevent and treat avian flu, known as H5N1, in humans. Made by Roche, Tamiflu is considered the best available treatment. Australia, Japan, and some European countries have built substantial stockpiles of the drug as their primary weapon against an avian flu pandemic.

Kawaoka and her colleagues isolated H5N1 from a 14-year-old Vietnamese patient after she had received a prophylactic dose (75 mg) once a day for three days. After amplification with polymerase chain reaction, the virus was sequenced. A large part of the virus population was found to have a histidine-to-tyrosine substitution at one position on its neuraminidase protein. This mutation is known to cause resistance to oseltamivir. All of the virus isolates from the patient were sensitive to zanamivir, which is sold under the name Relenza, an antiviral drug that is administered as an inhaled powder and can’t be given to children under seven.

Despite the virus’s resistance to a prophylactic dose, the Vietnamese patient recovered after receiving therapeutic doses of Tamiflu for seven days. There is evidence that she contracted avian flu while caring for her brother who was infected with H5N1, Kawaoka writes. The patient had no known contact with poultry, and the virus isolates from the patient and her brother were almost identical.

Even though the new findings are based on virus isolates from only one patient, they “raise the possibility that it might be useful to stockpile Relenza as well as oseltamivir in the event of an H5N1 influenza pandemic,” Kawaoka and coworkers note. Also, more efforts should be made to monitor the emergence of drug resistance in H5N1 virus, they add.



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