title: Surveillance of resistance to adamantanes among influenza A(H3N2) and A(H1N1) viruses isolated worldwide.
abstract: Our previous reports demonstrated an alarming increase in resistance to adamantanes among influenza A(H3N2) viruses isolated in 2001-2005. To continue monitoring drug resistance, we conducted a comprehensive analysis of influenza A(H3N2) and A(H1N1) viruses isolated globally in 2005-2006. The results obtained by pyrosequencing indicate that 96.4% (n=761) of A(H3N2) viruses circulating in the United States were adamantane resistant. Drug resistance has reached 100% among isolates from some Asian countries. Analysis of correlation between the appearance of drug resistance and the evolutionary pathway of the hemagglutinin (HA) gene suggests at least 2 separate introductions of resistance into circulating populations that gave rise to identifiable subclades. It also indicates that resistant A(H3N2) viruses may have emerged in Asia in late 2001. Among A(H1N1) viruses isolated worldwide, resistance reached 15.5% in 2005-2006; in the United States alone, it was 4.0%. Phylogenetic analysis of the HA and M genes indicates that the acquisition of resistance in A(H1N1) viruses can be linked to a specific genetic group and was not a result of reassortment between A(H3N2) and A(H1N1) viruses. The results of the study highlight the necessity of close monitoring of resistance to existing antivirals as wells as the need for new therapeutics.
authors.affiliation: Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
authors.forename: Varough M
authors.initials: VM
authors.lastname: Deyde
authors.forename: Xiyan
authors.initials: X
authors.lastname: Xu
authors.forename: Rick A
authors.initials: RA
authors.lastname: Bright
authors.forename: Michael
authors.initials: M
authors.lastname: Shaw
authors.forename: Catherine B
authors.initials: CB
authors.lastname: Smith
authors.forename: Ye
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yuelong
authors.initials: Y
authors.lastname: Shu
authors.forename: Larisa V
authors.initials: LV
authors.lastname: Gubareva
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Cox
authors.forename: Alexander I
authors.initials: AI
authors.lastname: Klimov
mesh_terms: D000547:Amantadine / Q000494:pharmacology*; D000998:Antiviral Agents / Q000494:pharmacology*; D024882:Drug Resistance, Viral; D014943:Global Health; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects* / Q000235:genetics; D053122:Influenza A Virus, H3N2 Subtype / Q000187:drug effects* / Q000235:genetics; D008826:Microbial Sensitivity Tests; D010802:Phylogeny; D012299:Rimantadine / Q000494:pharmacology*; D018571:Sentinel Surveillance
chemical_list: D000998:Antiviral Agents; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D012299:Rimantadine; D000547:Amantadine