Emergence of amantadine-resistant influenza A viruses: Epidemiological study

Hiroshi Suzuki, Reiko Saito, Hiroki Masuda, Hitoshi Oshitani, Mizuho Sato, Isamu Sato

Research output: Contribution to journalReview articlepeer-review

163 Citations (Scopus)


At present, three licensed antiviral influenza agents are available in Japan: amantadine, zanamivir, and oseltamivir. These antiviral agents can be used for controlling and preventing influenza, but they are not a substitute for vaccination. Amantadine is an antiviral drug with activity against influenza A viruses, but not influenza B viruses. Persons who have influenza A infection and who are treated with amantadine can shed sensitive viruses early in the course of treatment and later shed drug-resistant viruses, especially after 5-7 days of therapy. Such persons can benefit from therapy even when resistant viruses emerge. In screening for amantadine susceptibility, enzyme-linked immunoassays, plaque reduction assays, and TCID50/0.2 ml titration are employed. The molecular changes associated with resistance have been identified as single-nucleotide changes, leading to corresponding amino acid substitutions in one of four critical sites, amino acids 26, 27, 30, and 31, in the transmembrane region of the M2 protein. The polymerase chain reaction (PCR)-restriction fragment length polymorphism analysis method is quite useful. Resistant viruses have been circulated in outbreak situations at nursing homes where amantadine was used not only for treating influenza virus infection but also for Parkinson's disease. Measures should be taken to reduce contact, as much as possible, between persons taking and those not taking antiviral drugs for treatment or chemoprophylaxis.

Original languageEnglish
Pages (from-to)195-200
Number of pages6
JournalJournal of Infection and Chemotherapy
Issue number3
Publication statusPublished - 2003 Sept


  • Amantadine
  • Influenza virus
  • Resistant virus


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