title: Incidence of adamantane resistance among influenza A (H3N2) viruses isolated worldwide from 1994 to 2005: a cause for concern.
abstract: BACKGROUND
  Adamantanes have been used to treat influenza A virus infections for many years. Studies have shown a low incidence of resistance to these drugs among circulating influenza viruses; however, their use is rising worldwide and drug resistance has been reported among influenza A (H5N1) viruses isolated from poultry and human beings in Asia. We sought to assess adamantane resistance among influenza A viruses isolated during the past decade from countries participating in WHO's global influenza surveillance network.
  
  
  METHODS
  We analysed data for influenza field isolates that were obtained worldwide and submitted to the WHO Collaborating Center for Influenza at the US Centers for Disease Control and Prevention between Oct 1, 1994, and Mar 31, 2005. We used pyrosequencing, confirmatory sequence analysis, and phenotypic testing to detect drug resistance among circulating influenza A H3N2 (n=6524), H1N1 (n=589), and H1N2 (n=83) viruses.
  
  
  RESULTS
  More than 7000 influenza A field isolates were screened for specific aminoacid substitutions in the M2 gene known to confer drug resistance. During the decade of surveillance a significant increase in drug resistance was noted, from 0.4% in 1994-1995 to 12.3% in 2003-2004. This increase in the proportion of resistant viruses was weighted heavily by those obtained from Asia with 61% of resistant viruses isolated since 2003 being from people in Asia.
  
  
  CONCLUSIONS
  Our data raise concerns about the appropriate use of adamantanes and draw attention to the importance of tracking the emergence and spread of drug-resistant influenza A viruses.
authors.affiliation: Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Influenza Branch, Atlanta, GA, USA. rbright@cdc.gov
authors.forename: Rick A
authors.initials: RA
authors.lastname: Bright
authors.forename: Marie-jo
authors.initials: MJ
authors.lastname: Medina
authors.forename: Xiyan
authors.initials: X
authors.lastname: Xu
authors.forename: Gilda
authors.initials: G
authors.lastname: Perez-Oronoz
authors.forename: Teresa R
authors.initials: TR
authors.lastname: Wallis
authors.forename: Xiaohong M
authors.initials: XM
authors.lastname: Davis
authors.forename: Laura
authors.initials: L
authors.lastname: Povinelli
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Cox
authors.forename: Alexander I
authors.initials: AI
authors.lastname: Klimov
mesh_terms: D000218:Adamantane / Q000494:pharmacology*; D019943:Amino Acid Substitution; D000998:Antiviral Agents / Q000494:pharmacology*; D024882:Drug Resistance, Viral; D006801:Humans; D053122:Influenza A Virus, H3N2 Subtype; D009980:Influenza A virus / Q000187:drug effects* / Q000235:genetics; D014776:Virus Cultivation
chemical_list: D000998:Antiviral Agents; D000218:Adamantane