title: Emergence and spread of oseltamivir-resistant A(H1N1) influenza viruses in Oceania, South East Asia and South Africa.
abstract: The neuraminidase inhibitors (NAIs) are an effective class of antiviral drugs for the treatment of influenza A and B infections. Until recently, only a low prevalence of NAI resistance (<1%) had been detected in circulating viruses. However, surveillance in Europe in late 2007 revealed significant numbers of A(H1N1) influenza strains with a H274Y neuraminidase mutation that were highly resistant to the NAI oseltamivir. We examined 264 A(H1N1) viruses collected in 2008 from South Africa, Oceania and SE Asia for their susceptibility to NAIs oseltamivir, zanamivir and peramivir in a fluorescence-based neuraminidase inhibition assay. Viruses with reduced oseltamivir susceptibility were further analysed by pyrosequencing assay. The frequency of the oseltamivir-resistant H274Y mutant increased significantly after May 2008, resulting in an overall proportion of 64% (168/264) resistance among A(H1N1) strains, although this subtype represented only 11.6% of all isolates received during 2008. H274Y mutant viruses demonstrated on average a 1466-fold reduction in oseltamivir susceptibility and 527-fold reduction in peramivir sensitivity compared to wild-type A(H1N1) viruses. The mutation had no impact on zanamivir susceptibility. Ongoing surveillance is essential to monitor how these strains may spread or persist in the future and to evaluate the effectiveness of treatments against them.
authors.affiliation: WHO Collaborating Centre for Reference and Research on Influenza, Victoria, Australia. aeron.hurt@influenzacentre.org
authors.forename: Aeron C
authors.initials: AC
authors.lastname: Hurt
authors.forename: Joanne
authors.initials: J
authors.lastname: Ernest
authors.forename: Yi-Mo
authors.initials: YM
authors.lastname: Deng
authors.forename: Pina
authors.initials: P
authors.lastname: Iannello
authors.forename: Terry G
authors.initials: TG
authors.lastname: Besselaar
authors.forename: Chris
authors.initials: C
authors.lastname: Birch
authors.forename: Philippe
authors.initials: P
authors.lastname: Buchy
authors.forename: Malinee
authors.initials: M
authors.lastname: Chittaganpitch
authors.forename: Shu-Chun
authors.initials: SC
authors.lastname: Chiu
authors.forename: Dominic
authors.initials: D
authors.lastname: Dwyer
authors.forename: Aurélie
authors.initials: A
authors.lastname: Guigon
authors.forename: Bruce
authors.initials: B
authors.lastname: Harrower
authors.forename: Ip Peng
authors.initials: IP
authors.lastname: Kei
authors.forename: Tuckweng
authors.initials: T
authors.lastname: Kok
authors.forename: Cui
authors.initials: C
authors.lastname: Lin
authors.forename: Ken
authors.initials: K
authors.lastname: McPhie
authors.forename: Apandi
authors.initials: A
authors.lastname: Mohd
authors.forename: Remigio
authors.initials: R
authors.lastname: Olveda
authors.forename: Tony
authors.initials: T
authors.lastname: Panayotou
authors.forename: William
authors.initials: W
authors.lastname: Rawlinson
authors.forename: Lesley
authors.initials: L
authors.lastname: Scott
authors.forename: David
authors.initials: D
authors.lastname: Smith
authors.forename: Holly
authors.initials: H
authors.lastname: D'Souza
authors.forename: Naomi
authors.initials: N
authors.lastname: Komadina
authors.forename: Robert
authors.initials: R
authors.lastname: Shaw
authors.forename: Anne
authors.initials: A
authors.lastname: Kelso
authors.forename: Ian G
authors.initials: IG
authors.lastname: Barr
mesh_terms: D000146:Acids, Carbocyclic; D019943:Amino Acid Substitution / Q000235:genetics; D000998:Antiviral Agents / Q000494:pharmacology*; D001210:Asia, Southeastern; D016000:Cluster Analysis; D003517:Cyclopentanes / Q000494:pharmacology; D024882:Drug Resistance, Viral; D006146:Guanidines / Q000494:pharmacology; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects* / Q000302:isolation & purification; D007251:Influenza, Human / Q000821:virology*; D008826:Microbial Sensitivity Tests; D020125:Mutation, Missense; D009439:Neuraminidase / Q000235:genetics / Q000378:metabolism; D044349:Oceania; D053139:Oseltamivir / Q000494:pharmacology*; D010802:Phylogeny; D012367:RNA, Viral / Q000235:genetics; D017422:Sequence Analysis, DNA; D017385:Sequence Homology; D013019:South Africa; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D053243:Zanamivir / Q000494:pharmacology
chemical_list: D000146:Acids, Carbocyclic; D000998:Antiviral Agents; D003517:Cyclopentanes; D006146:Guanidines; D012367:RNA, Viral; D014764:Viral Proteins; D053139:Oseltamivir; C487630:NA protein, influenza A virus; D009439:Neuraminidase; D053243:Zanamivir; C414210:peramivir