title: Characteristics of a widespread community cluster of H275Y oseltamivir-resistant A(H1N1)pdm09 influenza in Australia.
abstract: BACKGROUND
  Oseltamivir resistance in A(H1N1)pdm09 influenza is rare, particularly in untreated community cases. Sustained community transmission has not previously been reported.
  
  
  METHODS
  Influenza specimens from the Asia-Pacific region were collected through sentinel surveillance, hospital, and general practitioner networks. Clinical and epidemiological information was collected on patients infected with oseltamivir-resistant viruses.
  
  
  RESULTS
  Twenty-nine (15%) of 191 A(H1N1)pdm09 viruses collected between May and September 2011 from Hunter New England (HNE), Australia, contained the H275Y neuraminidase substitution responsible for oseltamivir resistance. Only 1 patient had received oseltamivir before specimen collection. The resistant strains were genetically very closely related, suggesting the spread of a single variant. Ninety percent of cases lived within 50 kilometers. Three genetically similar oseltamivir-resistant variants were detected outside of HNE, including 1 strain from Perth, approximately 4000 kilometers away. Computational analysis predicted that neuraminidase substitutions V241I, N369K, and N386S in these viruses may offset the destabilizing effect of the H275Y substitution.
  
  
  CONCLUSIONS
  This cluster represents the first widespread community transmission of H275Y oseltamivir-resistant A(H1N1)pdm09 influenza. These cases and data on potential permissive mutations suggest that currently circulating A(H1N1)pdm09 viruses retain viral fitness in the presence of the H275Y mutation and that widespread emergence of oseltamivir-resistant strains may now be more likely.
authors.affiliation: WHO Collaborating Centre for Reference and Research on Influenza, North Melbourne, Victoria, Australia. aeron.hurt@influenzacentre.org
authors.forename: A C
authors.initials: AC
authors.lastname: Hurt
authors.forename: K
authors.initials: K
authors.lastname: Hardie
authors.forename: N J
authors.initials: NJ
authors.lastname: Wilson
authors.forename: Y M
authors.initials: YM
authors.lastname: Deng
authors.forename: M
authors.initials: M
authors.lastname: Osbourn
authors.forename: S K
authors.initials: SK
authors.lastname: Leang
authors.forename: R T C
authors.initials: RT
authors.lastname: Lee
authors.forename: P
authors.initials: P
authors.lastname: Iannello
authors.forename: N
authors.initials: N
authors.lastname: Gehrig
authors.forename: R
authors.initials: R
authors.lastname: Shaw
authors.forename: P
authors.initials: P
authors.lastname: Wark
authors.forename: N
authors.initials: N
authors.lastname: Caldwell
authors.forename: R C
authors.initials: RC
authors.lastname: Givney
authors.forename: L
authors.initials: L
authors.lastname: Xue
authors.forename: S
authors.initials: S
authors.lastname: Maurer-Stroh
authors.forename: D E
authors.initials: DE
authors.lastname: Dwyer
authors.forename: B
authors.initials: B
authors.lastname: Wang
authors.forename: D W
authors.initials: DW
authors.lastname: Smith
authors.forename: A
authors.initials: A
authors.lastname: Levy
authors.forename: R
authors.initials: R
authors.lastname: Booy
authors.forename: R
authors.initials: R
authors.lastname: Dixit
authors.forename: T
authors.initials: T
authors.lastname: Merritt
authors.forename: A
authors.initials: A
authors.lastname: Kelso
authors.forename: C
authors.initials: C
authors.lastname: Dalton
authors.forename: D
authors.initials: D
authors.lastname: Durrheim
authors.forename: I G
authors.initials: IG
authors.lastname: Barr
mesh_terms: D000293:Adolescent; D000328:Adult; D000998:Antiviral Agents / Q000494:pharmacology*; D001315:Australia / Q000453:epidemiology; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D017714:Community-Acquired Infections; D004279:DNA, Viral / Q000737:chemistry; D004196:Disease Outbreaks; D024882:Drug Resistance, Viral; D005260:Female; D006801:Humans; D007223:Infant; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects* / Q000235:genetics; D007251:Influenza, Human / Q000453:epidemiology / Q000821:virology*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D009439:Neuraminidase / Q000235:genetics; D053139:Oseltamivir / Q000494:pharmacology*; D010802:Phylogeny; D016415:Sequence Alignment; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D053139:Oseltamivir; D009439:Neuraminidase