Oseltamivir-resistant influenza viruses A (H1N1) during 2007-2009 influenza seasons, Japan

• Published in: Emerging infectious diseases Vol. 16; no. 6; pp. 926 - 935
• Main Authors: Ujike, Makoto, Shimabukuro, Kozue, Mochizuki, Kiku, Obuchi, Masatsugu, Kageyama, Tsutomu, Shirakura, Masayuki, Kishida, Noriko, Yamashita, Kazuyo, Horikawa, Hiroshi, Kato, Yumiko, Fujita, Nobuyuki, Tashiro, Masato, Odagiri, Takato
• Format: Journal Article
• Language: English
• Published: United States U.S. National Center for Infectious Diseases 01.06.2010; Centers for Disease Control and Prevention
• Subjects: Amantadine - pharmacology; Amino Acid Substitution; Antiviral Agents - pharmacology; Consumption data; Control; Dosage and administration; Drug Resistance, Viral; drug resistant; Drug therapy; Epidemiology; Genetic aspects; Hemagglutination Inhibition Tests; Humans; influenza; influenza A (H1N1); Influenza A Virus, H1N1 Subtype - drug effects; Influenza A Virus, H1N1 Subtype - genetics; Influenza A Virus, H1N1 Subtype - isolation & purification; Influenza viruses; Influenza, Human - epidemiology; Influenza, Human - virology; Japan - epidemiology; neuraminidase; Neuraminidase - antagonists & inhibitors; Neuraminidase - genetics; oseltamivir; Oseltamivir - pharmacology; Oseltamivir phosphate; Phylogeny; Physiological aspects; Seasons; Sequence Analysis, Protein; Swine influenza; Time Factors; Viral drug resistance; Viral Matrix Proteins - genetics; Viruses; Zanamivir - pharmacology; Japan
• ISSN: 1080-6040; 1080-6059
• DOI: 10.3201/eid1606.091623

To monitor oseltamivir-resistant influenza viruses A (H1N1) (ORVs) with H275Y in neuraminidase (NA) in Japan during 2 influenza seasons, we analyzed 3,216 clinical samples by NA sequencing and/or NA inhibition assay. The total frequency of ORVs was 2.6% (45/1,734) during the 2007-08 season and 99.7% (1,477/1,482) during the 2008-09 season, indicating a marked increase in ORVs in Japan during 1 influenza season. The NA gene of ORVs in the 2007-08 season fell into 2 distinct lineages by D354G substitution, whereas that of ORVs in the 2008-09 season fell into 1 lineage. NA inhibition assay and M2 sequencing showed that almost all the ORVs were sensitive to zanamivir and amantadine. The hemagglutination inhibition test showed that ORVs were antigenetically similar to the 2008-09 vaccine strain A/Brisbane/59/2007. Our data indicate that the current vaccine or zanamivir and amantadine are effective against recent ORVs, but continuous surveillance remains necessary.