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

Abstract

BACKGROUND:

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.

RESULTS:

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).

CONCLUSION:

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.

• Authors: Yoko Matsuzaki, Katsumi Mizuta, Yoko Aoki, Asuka Suto, Chieko Abiko, Kanako Sanjoh, Kanetsu Sugawara, Emi Takashita, Tsutomu Itagaki, Yuriko Katsushima, Makoto Ujike, Masatsugu Obuchi, Takato Odagiri, Masato Tashiro
• Journal: Virology journal (Virol J) Vol. 7 Pg. 53 (Mar 05 2010) ISSN: 1743-422X [Electronic] England
• PMID: 20202225 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antiviral Agents
• Viral Proteins
• Oseltamivir
• NA protein, influenza A virus
• Neuraminidase
• Zanamivir

Topics

• Adolescent
• Amino Acid Substitution (genetics)
• Animals
• Antiviral Agents (pharmacology, therapeutic use)
• Cell Line
• Child, Preschool
• Dogs
• Drug Resistance, Viral
• Humans
• Infant
• Influenza A Virus, H1N1 Subtype (classification, drug effects, growth & development, isolation & purification)
• Influenza, Human (drug therapy, virology)
• Japan
• Molecular Epidemiology
• Molecular Sequence Data
• Mutation, Missense
• Neuraminidase (genetics)
• Oseltamivir (pharmacology, therapeutic use)
• Phylogeny
• Sequence Analysis, DNA
• Treatment Outcome
• Viral Proteins (genetics)
• Virulence
• Zanamivir (therapeutic use)