title: Adamantane resistance in circulating human influenza A viruses from Alberta, Canada (1970-2007).
abstract: Mutation in one of five key amino acid residues (positions 26, 27, 30, 31 and 34) within the M2 protein of influenza A viruses, leads to resistance against the adamantane class of anti-influenza drugs. To investigate the emergence and prevalence of adamantane resistance in Alberta, Canada (between 1970 and 2007), 381 influenza A positive samples (original patient specimens) or isolates (virus cultured from patient specimens) were analyzed for changes in these critical amino acid residues. Our results show a significant increase in adamantane resistance in circulating H3N2 viruses in Alberta from 2005 and 2006 when compared with those from 2004 (p<0.001). Adamantane resistance peaked at 74% in 2006 and then decreased (to 38%) in 2007 (p=0.001). All resistant H3N2 viruses contained the substitution Ser to Asn at amino acid position 31 of the M2 protein with two viruses having an additional Ala to Val substitution at position 30. Resistance was not observed in the H1N1 viruses tested. Results presented here are concordant with, and extend, previous reports of increased resistance to adamantanes in Asia and North America in recent years. It is important to continue studies to evaluate circulating influenza A viruses for antiviral resistance markers to ensure their optimal use for prophylaxis and treatment of influenza.
authors.affiliation: Provincial Laboratory for Public Health (Microbiology), 3030 Hospital Drive, Calgary site, Calgary, Alberta, Canada T2N 4W4. K.Pabbaraju@provlab.ab.ca
authors.forename: Kanti
authors.initials: K
authors.lastname: Pabbaraju
authors.forename: Kevin C Y
authors.initials: KC
authors.lastname: Ho
authors.forename: Sallene
authors.initials: S
authors.lastname: Wong
authors.forename: Sandy
authors.initials: S
authors.lastname: Shokoples
authors.forename: Xiao-Li
authors.initials: XL
authors.lastname: Pang
authors.forename: Kevin
authors.initials: K
authors.lastname: Fonseca
authors.forename: Julie D
authors.initials: JD
authors.lastname: Fox
mesh_terms: D000218:Adamantane / Q000494:pharmacology*; D000416:Alberta; D000998:Antiviral Agents / Q000494:pharmacology*; D024882:Drug Resistance, Viral / Q000235:genetics*; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects* / Q000302:isolation & purification; D053122:Influenza A Virus, H3N2 Subtype / Q000187:drug effects* / Q000302:isolation & purification; D007251:Influenza, Human / Q000821:virology*; D020125:Mutation, Missense; D013997:Time Factors; D014763:Viral Matrix Proteins / Q000235:genetics; D000086082:Viroporin Proteins
chemical_list: D000218:Adamantane; D000998:Antiviral Agents; D014763:Viral Matrix Proteins; C488937:M2 protein, Influenza A virus; D000086082:Viroporin Proteins