Incidence of amantadine-resistant influenza A viruses in sentinel surveillance sites and nursing homes in Niigata, Japan

We surveyed the incidence of amantadine-resistant influenza A viruses both at sentinel surveillance sites and at nursing homes, and verified their typ es of change by partial nucleotide sequence analysis of the M2 protein. Fif ty-five influenza A viruses from 27 sentinel surveillance sites during six influenza seasons from 1993 to 1999, and 26 influenza A viruses from 5 nurs ing homes from 1996 to 1999 were examined for susceptibility to the drug by virus titration in the presence or absence of amantadine, While amantadine -resistant viruses were not found in sentinel surveillance sites, a high fr equency of resistance (8/26, 30.8%) in nursing homes was observed. Resistan t viruses can occur quickly and be transmitted when used in an outbreak sit uation at nursing homes, where amantadine is used either for neurologic ind ications or for influenza treatment. Eight resistant viruses had a single a mino acid change of the M2 protein at residue 30 or 31, In vitro, all 11 se nsitive viruses turned resistant after 3 or 5 passages in the presence of 2 mu g/ml amantadine, and they showed an amino acid change at residue 27, 30 , or 31, The predominant amino acid substitution in the M2 protein of resis tant viruses is Ser-31-Asp (a change at 31, serine to asparagine), The resu lts indicate that a monitoring system for amantadine-resistant influenza vi ruses should be established without delay in Japan.