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Journal of Clinical Microbiology, May 2009, p. 1424-1427, Vol. 47, No. 5
0095-1137/09/$08.00+0     doi:10.1128/JCM.02396-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Oseltamivir-Resistant Influenza A Viruses Circulating in Japan

Daisuke Tamura,^1* Keiko Mitamura,² Masahiko Yamazaki,³ Motoko Fujino,⁴ Mari Nirasawa,⁴ Kazuhiro Kimura,⁵ Maki Kiso,¹ Hideaki Shimizu,⁶ Chiharu Kawakami,⁷ Satoshi Hiroi,⁸ Kazuro Takahashi,⁸ Mami Hata,⁹ Hiroko Minagawa,⁹ Yoshiaki Kimura,¹⁰ Satoko Kaneda,¹⁰ Shigeo Sugita,¹¹ Taisuke Horimoto,¹ Norio Sugaya,¹² and Yoshihiro Kawaoka^1,13,14

Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo, Japan,¹ Department of Pediatrics, Eijyu General Hospital, Tokyo, Japan,² Department of Pediatrics, Zama Children's Clinic, Kanagawa, Japan,³ Department of Pediatrics, Saiseikai Central Hospital, Tokyo, Japan,⁴ Department of Pediatrics, Isehara Kyodo Hospital, Kanagawa, Japan,⁵ Kawasaki City Institute of Public Health, Kanagawa, Japan,⁶ Yokohama City Institute of Public Health, Kanagawa, Japan,⁷ Osaka Prefectural Institute of Public Health, Osaka, Japan,⁸ Aichi Prefectural Institute of Public Health, Aichi, Japan,⁹ Tottori Prefectural Institute of Public Health and Environmental Science, Tottori, Japan,¹⁰ Equine Research Institute, Japan Racing Association, Tochigi, Japan,¹¹ Department of Pediatrics, Keiyu Hospital, Kanagawa, Japan,¹² International Research Center for Infectious Disease, Institute of Medical Science, University of Tokyo, Tokyo, Japan,¹³ Department of Pathobiological Science, School of Veterinary Medicine, University of Wisconsin—Madison, Madison, Wisconsin,¹⁴

Received 14 December 2008/ Returned for modification 27 January 2009/ Accepted 17 February 2009

Surveillance studies of the influenza viruses circulating in Europe and other countries in 2007 and 2008 have revealed rates of resistance to oseltamivir of up to 67% among H1N1 viruses. In the present study, we examined 202 clinical samples obtained from patients infected with H1N1 virus in Japan in 2007 and 2008 for oseltamivir resistance and found that three were oseltamivir resistant (1.5%). The 50% inhibitory concentrations (IC₅₀s), as measured by a sialidase inhibition assay with these drug-resistant viruses, were >100-fold higher than those of the nonresistant viruses (median IC₅₀, 12.6 nmol/liter). The His274Tyr (strain N2 numbering) mutation of the neuraminidase protein, which is known to confer oseltamivir resistance, was detected in these three isolates. Phylogenetic analysis showed that one virus belonged to a lineage that is composed of drug-resistant viruses isolated in Europe and North America and that the other two viruses independently emerged in Japan. Continued surveillance studies are necessary to observe whether these viruses will persist.

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* Corresponding author. Mailing address: Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan. Phone: 81-3-5449-5310. Fax: 81-3-5449-5408. E-mail: kawaoka{at}ims.u-tokyo.ac.jp

Published ahead of print on 4 March 2009.

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Journal of Clinical Microbiology, May 2009, p. 1424-1427, Vol. 47, No. 5
0095-1137/09/$08.00+0     doi:10.1128/JCM.02396-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

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