Incidence of amantadine-resistant influenza A (genotype Ser-31-Asn) in nursing homes in Niigata, Japan

Abstract

The antiviral agent amantadine specifically inhibit influenza A virus infection, but the emergence of drug-resistant viruses occur more readily with amantadine treatment. In human influenza viruses, single amino acid changes at 4 sites spanning the transmembrane domain of the M2 protein can confer drug resistance. Amantadine was approved for treatment of Parkinson's disease in 1975, and for the influenza A virus infection in November 1998, in Japan. Annual consumption of amantadine for influenza treatment increased suddenly after the approval. According to our previous report, the predominant genotype of resistant virus is the substitution S-31-N in M2 both in vitro and in clinical samples, as in the other reports. Based on the above findings, we focused on single amino acid change at position 31 (genotype S-31-N) and applied polymerase chain-reaction restriction fragment length polymorphism (PCR-RFLP), directly from throat swab samples, by using primers that insert a restriction site for Sca I. With this technique, we surveyed the incidence of amantadine resistant viruses in nursing homes, Niigata, Japan. Thirty-one (22.0%) of 141 PCR positive samples from 8 nursing homes in 1998-99 season showed resistant patterns, and only 6 (19.4%) of them were after the administration of amantadine for treatment. All of these 8 nursing homes used amantadine for Parkinson's disease, but only half of them used the drug for influenza A infection. The incidence of resistant viruses was not significantly different from facilities with amantadine for influenza treatment to those without, 25.5% and 14.0% respectively. The occurrence of outbreaks and sporadic illness in those facilities, with different administration status were observed, but fortunately we could not find any evidence to relate the emergence of resistant viruses to the outbreaks. This is the first report that the resistant influenza viruses already exist in nursing facilities where amantadine was used for not only influenza but also Parkinson's disease in Japan.