title: Integrated Sentinel Surveillance Linking Genetic, Antigenic, and Epidemiologic Monitoring of Influenza Vaccine-Virus Relatedness and Effectiveness During the 2013-2014 Influenza Season.
abstract: BACKGROUND
  Canada's Sentinel Physician Surveillance Network links genetic, antigenic, and vaccine effectiveness (VE) measures in an integrated platform of influenza monitoring, described here for the 2013-2014 influenza season of resurgent A(H1N1)pdm09 and late-season type B activity.
  
  
  METHODS
  VE was estimated as [1 - odds ratio] × 100% and compared vaccination status between individuals who tested positive (cases) and those who tested negative (controls) for influenza virus. Vaccine-virus relatedness was assessed by genomic sequence analysis and hemagglutination inhibition assays.
  
  
  RESULTS
  Analyses included 1037 controls (of whom 33% were vaccinated) and 663 cases (of whom 14% were vaccinated). A total of 415 cases tested positive for A(H1N1)pdm09 virus, 15 tested positive for A(H3N2) virus, 191 tested positive for B/Yamagata-lineage virus, 6 tested positive for B/Victoria-lineage virus, and 36 tested positive for viruses of unknown subtype or lineage. A(H1N1)pdm09 viruses belonged to clade 6B, distinguished by a K163Q substitution, but remained antigenically similar to the A/California/07/2009-like vaccine strain, with an adjusted VE of 71% (95% confidence interval [CI], 58%-80%). Most B/Yamagata-lineage viruses (83%) clustered phylogenetically with the prior (ie, 2012-2013) season's B/Wisconsin/01/2010-like clade 3 vaccine strain, while only 17% clustered with the current (ie, 2013-2014) season's B/Massachusetts/02/2012-like clade 2 vaccine strain. The adjusted VE for B/Yamagata-lineage virus was 73% (95% CI, 57%-84%), with a lower VE obtained after partial calendar-time adjustment for clade-mismatched B/Wisconsin/01/2010-like virus (VE, 63%; 95% CI, 41%-77%), compared with that for clade-matched B/Massachusetts/02/2012-like virus (VE, 88%; 95% CI, 48%-97%). No A(H3N2) viruses clustered with the A/Texas/50/2012-like clade 3C.1 vaccine strain, and more than half were antigenically mismatched, but sparse data did not support VE estimation.
  
  
  CONCLUSIONS
  VE corresponded with antigenically conserved A(H1N1)pdm09 and lineage-matched B/Yamagata viruses with clade-level variation. Surveillance linking genotypic, phenotypic, and epidemiologic measures of vaccine-virus relatedness and effectiveness could better inform predictions of vaccine performance and reformulation.
authors.affiliation: British Columbia Centre for Disease Control University of British Columbia, Vancouver.
authors.forename: Danuta M
authors.initials: DM
authors.lastname: Skowronski
authors.affiliation: British Columbia Centre for Disease Control.
authors.forename: Catharine
authors.initials: C
authors.lastname: Chambers
authors.affiliation: British Columbia Centre for Disease Control.
authors.forename: Suzana
authors.initials: S
authors.lastname: Sabaiduc
authors.affiliation: Institut national de santé publique du Québec Laval University, Québec.
authors.forename: Gaston
authors.initials: G
authors.lastname: De Serres
authors.affiliation: Public Health Ontario.
authors.forename: Anne-Luise
authors.initials: AL
authors.lastname: Winter
authors.affiliation: University of Calgary.
authors.forename: James A
authors.initials: JA
authors.lastname: Dickinson
authors.affiliation: Public Health Ontario University of Toronto, Ontario.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Gubbay
authors.affiliation: University of Calgary Provincial Laboratory of Public Health, Calgary, Alberta.
authors.forename: Kevin
authors.initials: K
authors.lastname: Fonseca
authors.affiliation: Institut national de santé publique du Québec Universite de Montréal, Québec.
authors.forename: Hugues
authors.initials: H
authors.lastname: Charest
authors.affiliation: British Columbia Centre for Disease Control University of British Columbia, Vancouver.
authors.forename: Mel
authors.initials: M
authors.lastname: Krajden
authors.affiliation: University of British Columbia, Vancouver.
authors.forename: Martin
authors.initials: M
authors.lastname: Petric
authors.affiliation: University of Manitoba.
authors.forename: Salaheddin M
authors.initials: SM
authors.lastname: Mahmud
authors.affiliation: University of Manitoba Cadham Provincial Laboratory.
authors.forename: Paul
authors.initials: P
authors.lastname: Van Caeseele
authors.affiliation: National Microbiology Laboratory, Winnipeg, Canada.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Bastien
authors.affiliation: Public Health Ontario.
authors.forename: Alireza
authors.initials: A
authors.lastname: Eshaghi
authors.affiliation: University of Manitoba National Microbiology Laboratory, Winnipeg, Canada.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002170:Canada / Q000453:epidemiology; D002648:Child; D002675:Child, Preschool; D062665:Epidemiological Monitoring; D005260:Female; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000145:classification / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D009981:Influenza B virus / Q000145:classification / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D007251:Influenza, Human / Q000453:epidemiology / Q000517:prevention & control* / Q000821:virology*; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000235:genetics; D018571:Sentinel Surveillance; D017422:Sequence Analysis, DNA; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D007252:Influenza Vaccines; D012367:RNA, Viral
keywords: antigenic site; clade; genomic sequencing; hemagglutination inhibition; influenza; influenza A subtype; influenza B lineage; influenza vaccine; vaccine effectiveness