Purpose Neuraminidase inhibitors have been used for the treatment of both influenza A and B viral infections in children. Influenza viral infection occasionally shows pro- longed duration of the fever despite the use of neuraminidase inhibitors, suggesting drug resistance. It has been reported that mutations of the viruses are related with the drug resistance. Here, we studied association between prolonged fever and mutations in influenza B. Methods RNA was isolated from fixed nasopharyngeal swab of 206 patients with influenza in 2013/2014 season. The samples from ten patients having fever over 38˚C over 48hr were analyzed for neuraminidase sequences. Structural models reflecting the gene mutation of neuraminidase of influenza B virus (BNA) were analyzed. Results Patients infected with influenza B showed longer duration of fever on average than those with influenza A. Sequences of BNAs from the patients with prolonged fever were different from that of the strain for vaccine (B/ Massachusetts/02/2012). Two of the sequences in the samples M2-1 and K41-1 contained mutations for potential drug resistance: S99N, T106I, K125T and S295R in the sample M2-1 and I262M, V271T, K/E272Q, E320K, D342G and M375K in the K41-1. Structural models of BNA suggested that R295 of the M2-1 and Q272 and K375 of the K41-1 may be responsible for the drug resistance. Conclusions Drug-resistant mechanism of BNA was clarified by using structural model analysis. Proper use of neuraminidase inhibitors against influenza virus infection is necessary in clinical setting.

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