Monitoring and Characterization of Oseltamivir-Resistant Pandemic (H1N1)

DOI: 10.3201/eid1703.101188
Suggested citation for this article: Ujike M, Ejima M, Anraku A, Shimabukuro K, Obuchi M, Noriko Kishida N, et al. Monitoring and characterization of oseltamivir-resistant pandemic (H1N1) 2009 virus, Japan, 2009–2010 Emerg Infect Dis. 2011 Mar; [Epub ahead of print]

Monitoring and Characterization of Oseltamivir-Resistant Pandemic (H1N1)
2009 Virus, Japan, 2009–2010

Makoto Ujike, Miho Ejima, Akane Anraku, Kozue Shimabukuro, Masatsugu Obuchi, Noriko Kishida, Xu Hong, Emi Takashita, Seiichiro Fujisaki, Kazuyo Yamashita, Hiroshi Horikawa, Yumiko Kato, Akio Oguchi, Nobuyuki Fujita, Masato Tashiro, Takato Odagiri, and the Influenza Virus Surveillance Group of Japan1


Author affiliations: National Institute of Infectious Diseases, Tokyo, Japan (M. Ujike, M. Ejima, A. Anraku, K.
Shimabukuro, M. Obuchi, N. Kishida, X. Hong, E. Takashita, S. Fujisaki, K. Yamashita, M. Tashiro, T. Odagiri); and
National Institute of Technology and Evaluation, Tokyo, Japan (H. Horikawa, Y. Kato, A. Oguchi, N. Fujita)
1Members of the Influenza Virus Surveillance Group of Japan are listed at the end of this article.

To monitor and characterize oseltamivir-resistant (OR) pandemic (H1N1) 2009 virus with the H275Y mutation, we analyzed 4,307 clinical specimens from Japan by neuraminidase (NA) sequencing or inhibition assay; 61 OR pandemic (H1N1) 2009 viruses were detected. NA inhibition assay and M2 sequencing indicated that OR pandemic (H1N1) 2009 virus was resistant to M2 inhibitors, but sensitive to zanamivir. Full-genome sequencing showed OR and oseltamivir-sensitive (OS) viruses had high sequence similarity, indicating that domestic OR virus was derived from OS pandemic (H1N1) 2009 virus.

Hemagglutination inhibition test demonstrated that OR and OS pandemic (H1N1) 2009 viruses were antigenically similar to the A/California/7/2009 vaccine strain. Of 61 case-patients with OR viruses, 45 received oseltamivir in treatment, and 10 received it in prophylaxis, suggesting that most cases emerged sporadically from OS pandemic (H1N1) 2009, due to selective pressure. No evidence of sustained spread of OR pandemic (H1N1) 2009 was found in Japan; however, 2 suspected incidents of human-to-human transmission were reported.

full-text, pdf 24 pages:
http://www.cdc.gov/eid/content/17/3/pdfs/10-1188.pdf?source=govdelivery