title: A sentinel platform to evaluate influenza vaccine effectiveness and new variant circulation, Canada 2010-2011 season.
abstract: BACKGROUND
  During the 2010-2011 winter, a large number of outbreaks due to influenza A/H3N2 at long-term care facilities, including higher-than-expected attack rates among vaccinated staff, were reported in some regions of Canada. Interim analysis from the community-based sentinel surveillance system showed circulating H3N2 variants and suboptimal vaccine effectiveness (VE), assessed here for the entire season's data set.
  
  
  METHODS
  Nasal/nasopharyngeal swabs and epidemiologic details were collected from patients presenting to sentinel sites within 7 days of onset of influenza-like illness. Cases tested positive for influenza by real-time reverse-transcription polymerase chain reaction; controls tested negative. Odds ratios for medically attended, laboratory-confirmed influenza in vaccinated vs nonvaccinated participants were used to derive adjusted VE. Viruses were characterized by hemagglutination inhibition (HI), and the hemagglutinin genes of a subset were sequenced to explore vaccine relatedness.
  
  
  RESULTS
  Final 2010-2011 VE analysis included 1718 participants (half aged 20-49 years), 93 with A(H1N1)pdm09, 408 with A/H3N2, and 199 with influenza B. Among adults aged 20-49 years, adjusted VE was 65% (95% confidence interval [CI], 8%-87%) for A(H1N1)pdm09 and 66% (95% CI, 10%-87%) for influenza B. Vaccine effectiveness was substantially lower for A/H3N2, at 39% (95% CI, 0%-63%). Phylogenetic analysis identified 2 circulating H3N2 variant clades, A/HongKong/2121/2010 (87%) and A/Victoria/208/2009 (11%), bearing multiple amino acid substitutions at antigenic sites (12 and 8, respectively) compared with the H3N2 vaccine component used in Canada (A/Victoria/210/2009[NYMC X-187]). However, HI characterized all H3N2 isolates as well matched to the vaccine.
  
  
  CONCLUSIONS
  Public health observations of increased facility H3N2 outbreaks were consistent with the sentinel network's detection of genetic variants and suboptimal VE but not with conventional HI characterization. We highlight the utility of a multicomponent sentinel surveillance platform that incorporates genotypic, phenotypic, and epidemiologic indicators into the assessment of influenza virus, new variant circulation, vaccine relatedness, and VE.
authors.affiliation: British Columbia Centre for Disease Control, Provincial Health Services Authority, Vancouver, Canada. danuta.skowronski@bccdc.ca
authors.forename: Danuta M
authors.initials: DM
authors.lastname: Skowronski
authors.forename: Naveed Z
authors.initials: NZ
authors.lastname: Janjua
authors.forename: Gaston
authors.initials: G
authors.lastname: De Serres
authors.forename: Anne-Luise
authors.initials: AL
authors.lastname: Winter
authors.forename: James A
authors.initials: JA
authors.lastname: Dickinson
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Gardy
authors.forename: Jonathan
authors.initials: J
authors.lastname: Gubbay
authors.forename: Kevin
authors.initials: K
authors.lastname: Fonseca
authors.forename: Hugues
authors.initials: H
authors.lastname: Charest
authors.forename: Natasha S
authors.initials: NS
authors.lastname: Crowcroft
authors.forename: Monique Douville
authors.initials: MD
authors.lastname: Fradet
authors.forename: Nathalie
authors.initials: N
authors.lastname: Bastien
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Mel
authors.initials: M
authors.lastname: Krajden
authors.forename: Suzana
authors.initials: S
authors.lastname: Sabaiduc
authors.forename: Martin
authors.initials: M
authors.lastname: Petric
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002170:Canada / Q000453:epidemiology; D002648:Child; D002675:Child, Preschool; D005260:Female; D006385:Hemagglutination Inhibition Tests; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D053122:Influenza A Virus, H3N2 Subtype / Q000145:classification / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D007251:Influenza, Human / Q000453:epidemiology* / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D008297:Male; D008875:Middle Aged; D009305:Nasopharynx / Q000821:virology; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018571:Sentinel Surveillance; D017422:Sequence Analysis, DNA; D055815:Young Adult
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines