Correspondence

Amantadine-Resistant Influenza A (H3N2) Virus in Japan, 2005–2006

N Engl J Med 2007; 356:312-313January 18, 2007

Article

To the Editor:

Strains of influenza A (H3N2) virus with a specific mutation (Ser31Asn) have recently shown a dramatic increase in resistance to amantadine in communities in Asia and North America. This resistance in 70 to 90% of strains has occurred despite the absence of sustained selective drug pressure.1,2 We conducted a multicenter study to assess the prevalence of such resistance during the 2005–2006 influenza season in Japan. The study included molecular analysis of the hemagglutinin gene of resistant and sensitive influenza A (H3N2) viruses.

We examined a total of 415 isolates of influenza A virus, sampled from November 2005 to April 2006, for amantadine resistance. Of these samples, 231 of 354 influenza A (H3N2) viral isolates (65.3%) were amantadine resistant, with a Ser31Asn change in the M2 gene. The prevalence of resistance ranged from 36.8 to 100%, according to the area in Japan. However, none of 61 influenza A (H1N1) viral isolates were resistant. Analyses of the hemagglutinin gene in influenza A (H3N2) viral isolates showed two distinct clades: all amantadine-resistant viruses were in clade N, and all amantadine-sensitive viruses were in clade S.

The clinical presentation did not differ between patients shedding clade N virus and those shedding clade S virus. None of the patients had received previous treatment with amantadine. The numbers of patients with influenza at the medical facilities participating in the study were similar to those in the past, despite a high proportion of resistance. Clade N viruses were also found in other countries, suggesting that this strain predominated not only in Japan but also in other parts of Asia and in North America and Oceania during the 2005–2006 season.3,4

Reiko Saito, M.D., Ph.D.
Danjuan Li, M.D.
Hiroshi Suzuki, M.D., Ph.D.
Niigata University, Niigata City 951-8510, Japan
jasmine@med.niigata-u.ac.jp

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Citing Articles (16)

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   Jila Yavarian, Talat Mokhtari Azad, Xiang Zheng, Victoria Gregory, Yi Pu Lin, Alan Hay. (2010) Amantadine resistance in relation to the evolution of influenza A(H3N2) viruses in Iran. Antiviral Research 88:2, 193-196
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   S.-R. Shih, J.-T. Horng, L. L. M. Poon, T.-C. Chen, J.-Y. Yeh, H.-P. Hsieh, S.-N. Tseng, C. Chiang, W.-L. Li, Y.-S. Chao, J. T.-A. Hsu. (2010) BPR2-D2 targeting viral ribonucleoprotein complex-associated function inhibits oseltamivir-resistant influenza viruses. Journal of Antimicrobial Chemotherapy 65:1, 63-71
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   Varough Deyde, Rebecca Garten, Tiffany Sheu, Catherine Smith, Allison Myrick, John Barnes, Xiyan Xu, Michael Shaw, Alexander Klimov, Larisa Gubareva. (2009) Genomic events underlying the changes in adamantane resistance among influenza A(H3N2) viruses during 2006-2008. Influenza and Other Respiratory Viruses 3:6, 297-314
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   Natalia Goñi, José Russi, Juan Cristina. (2009) Human influenza A viruses isolated in South America: Genetic relations, adamantane resistance and vaccine strain match. Infection, Genetics and Evolution 9:2, 229-234
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   Varough M. Deyde, Margaret Okomo-Adhiambo, Tiffany G. Sheu, Teresa R. Wallis, Alicia Fry, Nila Dharan, Alexander I. Klimov, Larisa V. Gubareva. (2009) Pyrosequencing as a tool to detect molecular markers of resistance to neuraminidase inhibitors in seasonal influenza A viruses. Antiviral Research 81:1, 16-24
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    Julian W. Tang, Karry L.K. Ngai, Jasper C.L. Wong, Wai Y. Lam, Paul K.S. Chan. (2008) Emergence of adamantane-resistant influenza A(H3N2) viruses in Hong Kong between 1997 and 2006. Journal of Medical Virology 80:5, 895-901
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    Varough M. Deyde, Rebecca Garten, Tiffany G. Sheu, Larisa V. Gubareva, Alexander I. Klimov. (2008) Reply to Saito et al.. The Journal of Infectious Diseases 197:4, 632-633
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