Emerg Infect Dis. Rare Influenza A (H3N2) Variants with Reduced Sensitivity to Antiviral Drugs

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Rare Influenza A (H3N2) Variants with Reduced Sensitivity to Antiviral Drugs (Emerg Infect Dis., abstract, edited)

[Source Full PDF Document: LINK. EDITED.]

DOI: 10.3201/eid1603.091321
Suggested citation for this article: Dapat C, Suzuki Y, Saito R, Kyaw Y, Myint YY, Lin N, et al. Rare influenza A (H3N2) variants with reduced sensitivity to antiviral drugs. Emerg Infect Dis. 2010 Mar; [Epub ahead of print]

Rare Influenza A (H3N2) Variants with Reduced Sensitivity to Antiviral Drugs

Clyde Dapat,1 Yasushi Suzuki,1 Reiko Saito, Yadanar Kyaw, Yi Yi Myint, Nay Lin, Htun Naing Oo, Khin Yi Oo, Ne Win, Makoto Naito, Go Hasegawa, Isolde C. Dapat, Hassan Zaraket, Tatiana Baranovich, Makoto Nishikawa, Takehiko Saito, and Hiroshi Suzuki

Author affiliations: Niigata University, Niigata, Japan (C. Dapat, Y. Suzuki, R. Saito, M. Naito, G. Hasegawa, I.C. Dapat, H. Zaraket, T. Baranovich, H. Suzuki); National Institute of Animal Health, Tsukuba City, Japan (T. Saito); Niigata Prefectural Institute of Public Health and Environmental Sciences, Niigata (M. Nishikawa); Sanpya Hospital, Yangon, Myanmar (Y. Kyaw); National Health Laboratory, Yangon (K.Y. Oo, N. Win); and Central Myanmar Department of Medical Research, Nay Pyi Taw, Myanmar (Y.Y. Myint, N. Lin, H.N. Oo)
1These authors contributed equally to this article.


In 2007 and 2008 in Myanmar, we detected influenza viruses A (H3N2) that exhibited reduced sensitivity to both zanamivir and amantadine. These rare and naturally occurring viruses harbored a novel Q136K mutation in neuraminidase and S31N mutation in M2.

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Re: Emerg Infect Dis. Rare Influenza A (H3N2) Variants with Reduced Sensitivity to Antiviral Drugs

More snips from the study:

We searched the database for NA sequences of influenza viruses A (H3N2) with Q136K mutation that are available on GenBank. Of the 3,381 sequences obtained, 4 sequences from human influenza, which were isolated in 1995, 2003, 2004, and 2007, and 1 sequence from swine influenza, which was isolated in Japan in 1997, contained the Q136K substitution.

Sequences from Q136K mutants isolated before 2007 showed no mutations in the M2 gene. The data indicate that these viruses occur naturally because some of the isolates in the database were obtained before introduction of zanamivir into clinical practice in 1999 in Australia, New Zealand, United States, and Europe (9,13). In addition, Myanmar patients who shed these Q136K viruses did not receive any NAIs. The clinical relevance of Q136K mutants is unknown. Further study is needed to evaluate the effectiveness of zanamivir in patients infected with Q136K mutants.

Continued monitoring of viruses with reduced sensitivity to NAI and adamantanes is needed, and routine surveillance should include both phenotypic and genotypic assays. The Q136K substitution in NA should be used as a molecular marker associated with reduced NAI susceptibility not only in subtype H1N1 isolates but also among subtype H3N2 isolates.