A two-year survey of the oseltamivir-resistant influenza A(H1N1) virus in Yamagata, Japan and the clinical effectiveness of oseltamivir and zanamivir

• Published in: Virology journal 2010-03, Vol.7 (1), p.53-53, Article 53
• Main Authors: Matsuzaki, Yoko, Mizuta, Katsumi, Aoki, Yoko, Suto, Asuka, Abiko, Chieko, Sanjoh, Kanako, Sugawara, Kanetsu, Takashita, Emi, Itagaki, Tsutomu, Katsushima, Yuriko, Ujike, Makoto, Obuchi, Masatsugu, Odagiri, Takato, Tashiro, Masato
• Format: Article
• Language: English
• Subjects: Adolescent; Amino Acid Substitution - genetics; Animals; Antiviral Agents - pharmacology; Antiviral Agents - therapeutic use; Cell Line; Child, Preschool; Dogs; Drug Resistance, Viral; Experiments; Genes; Humans; Infant; Infections; Infectious diseases; Influenza; Influenza A Virus, H1N1 Subtype - classification; Influenza A Virus, H1N1 Subtype - drug effects; Influenza A Virus, H1N1 Subtype - growth & development; Influenza A Virus, H1N1 Subtype - isolation & purification; Influenza, Human - drug therapy; Influenza, Human - virology; Japan; Molecular Epidemiology; Molecular Sequence Data; Mutation; Mutation, Missense; Neuraminidase - genetics; Oseltamivir - pharmacology; Oseltamivir - therapeutic use; Pediatrics; Phylogenetics; Phylogeny; Seasons; Sequence Analysis, DNA; Software; Studies; Treatment Outcome; Trees; University faculty; Viral Proteins - genetics; Virulence; Viruses; Zanamivir - therapeutic use
• ISSN: 1743-422X; 1743-422X
• DOI: 10.1186/1743-422x-7-53

Oseltamivir is the preferred antiviral drug for influenza, but oseltamivir-resistant A(H1N1) viruses have circulated worldwide since the 2007-2008 influenza season. We aimed to determine the rate of oseltamivir resistance among A(H1N1) isolates from Yamagata, Japan, to compare the virological characteristics between isolates from the 2007-2008 and 2008-2009 seasons, and to evaluate the clinical effectiveness of oseltamivir. Oseltamivir resistance, determined by detecting the H275Y mutation in the neuraminidase (NA) gene, was observed in 2.5% (2 of 79) and 100% (77 of 77) of isolates from the 2007-2008 and 2008-2009 seasons, respectively. Antigenic analysis suggested that antigenically different variants of A(H1N1) viruses circulated in the 2008-2009 season. Growth testing demonstrated that the ability of the 2008-2009 isolates to replicate in MDCK cells was similar to those of the oseltamivir-susceptible isolates from the 2007-2008 season. A phylogenetic analysis revealed that two oseltamivir-resistant viruses isolated in the 2007-2008 season were closely related to other oseltamivir-susceptible viruses in Yamagata but were different from oseltamivir-resistant viruses isolated in Europe and North America in the 2007-2008 season. The oseltamivir-resistant viruses isolated in Japan in the 2008-2009 season were phylogenetically similar to oseltamivir-resistant isolates from Europe and North America during the 2007-2008 season. Furthermore, the median duration of fever after the start of oseltamivir treatment was significantly longer in oseltamivir-resistant cases (2 days; range 1-6 days) than in oseltamivir-susceptible cases (1.5 days: range 1-2 days) (P = 0.0356). Oseltamivir-resistant A(H1N1) isolates from Yamagata in the 2007-2008 season might have acquired resistance through the use of oseltamivir, and the 2008-2009 oseltamivir-resistant isolates might have been introduced into Japan and circulated throughout the country. Influenza surveillance to monitor oseltamivir-resistance would aid clinicians in determining an effective antiviral treatment strategy.