Amantadine-resistant influenza A virus in Taiwan.
OBJECTIVE
Amantadine and rimantadine have been used for treatment and prophylaxis of influenza A virus infection. We examined the amantadine susceptibility of field isolates of influenza A virus in Taiwan from 1996 to 1998 to monitor the presence of resistant strains.


METHODS
Eighty-four field isolates of influenza A virus were examined for resistance to amantadine by plaque inhibition assay. Virus isolates with amantadine 50% inhibitory concentrations (IC50) greater than 0.9 microgram were chosen for sequence analysis of the M gene that is the molecular target for amantadine/rimantadine. Reverse transcription-polymerase chain reaction (RT-PCR) was used to amplify the viral RNA. RT-PCR products were examined and purified by agarose gel electrophoresis for further sequence analysis. The Genetics Computer Group Sequence Analysis Package and the neighbor-joining method listed in the Molecular Evolutionary Genetic Analysis package were used for phylogenetic analysis.


RESULTS
One field strain was amantadine resistant (IC50 > 10 micrograms/mL), with a mutation (position 31, serine to asparagine) in the M2 protein. The resistant virus was isolated from a non-immunocompromised child without a history of amantadine/rimantadine treatment. None of the family members reported previous exposure to amantadine/rimantadine.


CONCLUSIONS
In this series, amantadine-resistant influenza A (H1N1) virus was isolated from a non-immunocompromised Taiwanese child without a known history of exposure to this drug. Resistant field isolates were rare. Due to the increasing use of amantadine/rimantadine in Taiwan, continued surveillance for amantadine/rimantadine-resistant influenza A viruses is warranted.
Shih
S R
SR
School of Medical Technology, Chang Gung University, Clinical Virology Laboratory, Chang Gung Memorial Hospital, Tao-Yuan.
Lee
C N
CN
Tsai
H R
HR
Chen
G W
GW
Tsao
K C
KC
D000547:Amantadine / Q000494:pharmacology*; D000595:Amino Acid Sequence; D000998:Antiviral Agents / Q000494:pharmacology*; D001483:Base Sequence; D024882:Drug Resistance, Viral; D006801:Humans; D009980:Influenza A virus / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data
D000998:Antiviral Agents; D000547:Amantadine