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Influenza Other Respir Viruses. 2013 Nov;7(6):1390-9. doi: 10.1111/irv.12132. Epub 2013 Jun 8.

Characterization of neuraminidase inhibitor-resistant influenza A(H1N1)pdm09 viruses isolated in four seasons during pandemic and post-pandemic periods in Japan.

Author information

1
Laboratory of Influenza Virus Surveillance, Influenza Virus Research Center, National Institute of Infectious Diseases, Tokyo, Japan.

Abstract

BACKGROUND/OBJECTIVES:

Japan has the highest frequency of neuraminidase (NA) inhibitor use against influenza in the world. Therefore, Japan could be at high risk of the emergence and spread of NA inhibitor-resistant viruses. The aim of this study was to monitor the emergence of NA inhibitor-resistant viruses and the possibility of human-to-human transmission during four influenza seasons in Japan.

METHODS:

To monitor antiviral-resistant A(H1N1)pdm09 viruses, we examined viruses isolated in four seasons from the 2008-2009 season through the 2011-2012 season in Japan by allelic discrimination, NA gene sequencing, and NA inhibitor susceptibility.

RESULTS:

We found that 157 (1·3%) of 12 026 A(H1N1)pdm09 isolates possessed an H275Y substitution in the NA protein that confers about 400- and 140-fold decreased susceptibility to oseltamivir and peramivir, respectively, compared with 275H wild-type viruses. The detection rate of resistant viruses increased from 1·0% during the pandemic period to 2·0% during the post-pandemic period. The highest detection rate of the resistant viruses was found in patients who were 0-9 years old. Furthermore, among the cases with resistant viruses, the percentage of no known exposure to antiviral drugs increased from 16% during the pandemic period to 44% during the post-pandemic period, implying that suspected human-to-human transmission of the resistant viruses gradually increased in the post-pandemic period.

CONCLUSIONS:

A(H1N1)pdm09 viruses resistant to oseltamivir and peramivir were sporadically detected in Japan, but they did not spread throughout the community. No viruses resistant to zanamivir and laninamivir were detected.

KEYWORDS:

Influenza A(H1N1)pdm09 virus; neuraminidase inhibitor resistant; neuraminidase inhibitor susceptibility

PMID:
23745712
PMCID:
PMC4634248
DOI:
10.1111/irv.12132
[Indexed for MEDLINE]
Free PMC Article

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