Epidemiologic study of influenza infection in Okinawa, Japan, from 2001 to 2007: changing patterns of seasonality and prevalence of amantadine-resistant influenza A virus.

To clarify seasonal influenza patterns and the prevalence of amantadine-resistant influenza A viruses in Okinawa, located at the southern extremity of Japan in a subtropical climate, we conducted a laboratory-based study of influenza virus infections from 2001 to 2007. The annual outbreaks tended to show two peaks in Okinawa, in summer and winter, although the main islands of Japan, located in a temperate climate area, showed only winter influenza activity. Epidemic types and subtypes in Okinawa mostly matched those on the main islands of Japan in winter and those in Taiwan in summer. Rates of amantadine resistance dramatically increased, from 7.3% in the November 2002-to-March 2003 season to 90.0% in summer 2005, and a similarly high rate of resistance continued for the rest of the study period. Phylogenetic analysis of the hemagglutinin gene of A/H3N2 isolates collected from 2002 to 2007 revealed a monophyletic lineage that was divided into four period groups. Each group included amantadine-sensitive and -resistant viruses within independent clusters. In the November 2005-to-March 2006 season, all of the amantadine-resistant viruses were clustered in clade N, with dual (position 193 and 225) amino acid mutations in their HA1 subunits. In 2005, clade N amantadine-resistant viruses existed in Okinawa several months before the circulation of this clade on the main islands of Japan. In conclusion, surveillance in Okinawa to monitor influenza virus circulation is important for elucidating the dynamics of virus transmission in a border area between temperate and subtropical areas, as Okinawa is one of the best sentinel points in Japan.