title: High prevalence of amantadine-resistance influenza a (H3N2) in six prefectures, Japan, in the 2005-2006 season.
abstract: Substantial increase in amantadine-resistant influenza A (H3N2) was reported in Asia and North America in 2005. In this study the frequency and genetic characteristics of amantadine-resistant influenza A, circulated in Japan in 2005-2006 season, were investigated. Isolates were tested by amantadine susceptibility test (TCID(50)/0.2 ml method), and sequencing of the M2 gene to identify mutations that confer resistance. Additionally, the hemagglutinin (HA) and neuraminidase (NA) genes of the viruses were examined. In total, 415 influenza A isolates from six prefectures were screened, and 231 (65.3%) of 354 influenza A (H3N2) were amantadine-resistant, with a serine to asparagine (S31N) change in the M2 gene. However, none of 61 A (H1N1) isolates were resistant. In addition, genetic analyses of the HA gene showed all amantadine-resistant viruses clustered in one (named clade N), possessing specific double mutations at 193, serine to phenylalanine (S193F), and at 225, asparatic acid to asparagine (D225N), and sensitive viruses belonged to another group (clade S). The clinical presentations at the clinical visit did not differ between patients shedding clade N virus and those shedding clade S virus. None of the patients had received previous treatment with amantadine. The results indicate an unusually high prevalence and wide circulation of the amantadine-resistance influenza A (H3N2) in Japan in the 2005-2006 season. These strains had the characteristic double mutations in the HA, in addition to the M2 mutation responsive for resistance. Antiviral resistance monitoring should be intensified and maintained for rapid feedback into treatment strategies, and selection of alternative therapeutic agents.
authors: Department of Public Health, Niigata University, Graduate School of Medical and Dental Science, Niigata, Japan. jasmine@med.niigata-u.ac.jp
authors: Reiko
authors: R
authors: Saito
authors: Danjuan
authors: D
authors: Li
authors: Yasushi
authors: Y
authors: Suzuki
authors: Isamu
authors: I
authors: Sato
authors: Hironori
authors: H
authors: Masaki
authors: Hidekazu
authors: H
authors: Nishimura
authors: Takashi
authors: T
authors: Kawashima
authors: Yutaka
authors: Y
authors: Shirahige
authors: Chieko
authors: C
authors: Shimomura
authors: Norichika
authors: N
authors: Asoh
authors: Satoshi
authors: S
authors: Degawa
authors: Hidefumi
authors: H
authors: Ishikawa
authors: Maki
authors: M
authors: Sato
authors: Yugo
authors: Y
authors: Shobugawa
authors: Hiroshi
authors: H
authors: Suzuki
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000547:Amantadine / Q000494:pharmacology*; D019943:Amino Acid Substitution; D000998:Antiviral Agents / Q000494:pharmacology*; D002648:Child; D024882:Drug Resistance, Viral; D005260:Female; D005814:Genes, Viral / Q000235:genetics; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics; D006801:Humans; D053122:Influenza A Virus, H3N2 Subtype / Q000187:drug effects* / Q000235:genetics*; D007251:Influenza, Human / Q000453:epidemiology*; D007564:Japan / Q000453:epidemiology; D008297:Male; D017720:Molecular Epidemiology; D009439:Neuraminidase / Q000235:genetics; D010802:Phylogeny; D017354:Point Mutation; D014763:Viral Matrix Proteins / Q000235:genetics; D014764:Viral Proteins / Q000235:genetics; D000086082:Viroporin Proteins
chemical_list: D000547:Amantadine; D000998:Antiviral Agents; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D009439:Neuraminidase; D014763:Viral Matrix Proteins; D014764:Viral Proteins; C488937:M2 protein, Influenza A virus; D000086082:Viroporin Proteins; C483468:hemagglutinin, human influenza A virus