title: Association between the 2008-09 seasonal influenza vaccine and pandemic H1N1 illness during Spring-Summer 2009: four observational studies from Canada.
abstract: BACKGROUND
  In late spring 2009, concern was raised in Canada that prior vaccination with the 2008-09 trivalent inactivated influenza vaccine (TIV) was associated with increased risk of pandemic influenza A (H1N1) (pH1N1) illness. Several epidemiologic investigations were conducted through the summer to assess this putative association.
  
  
  RESULTS
  
  
  
  METHODS
  (1) test-negative case-control design based on Canada's sentinel vaccine effectiveness monitoring system in British Columbia, Alberta, Ontario, and Quebec; (2) conventional case-control design using population controls in Quebec; (3) test-negative case-control design in Ontario; and (4) prospective household transmission (cohort) study in Quebec. Logistic regression was used to estimate odds ratios for TIV effect on community- or hospital-based laboratory-confirmed seasonal or pH1N1 influenza cases compared to controls with restriction, stratification, and adjustment for covariates including combinations of age, sex, comorbidity, timeliness of medical visit, prior physician visits, and/or health care worker (HCW) status. For the prospective study risk ratios were computed. Based on the sentinel study of 672 cases and 857 controls, 2008-09 TIV was associated with statistically significant protection against seasonal influenza (odds ratio 0.44, 95% CI 0.33-0.59). In contrast, estimates from the sentinel and three other observational studies, involving a total of 1,226 laboratory-confirmed pH1N1 cases and 1,505 controls, indicated that prior receipt of 2008-09 TIV was associated with increased risk of medically attended pH1N1 illness during the spring-summer 2009, with estimated risk or odds ratios ranging from 1.4 to 2.5. Risk of pH1N1 hospitalization was not further increased among vaccinated people when comparing hospitalized to community cases.
  
  
  CONCLUSIONS
  Prior receipt of 2008-09 TIV was associated with increased risk of medically attended pH1N1 illness during the spring-summer 2009 in Canada. The occurrence of bias (selection, information) or confounding cannot be ruled out. Further experimental and epidemiological assessment is warranted. Possible biological mechanisms and immunoepidemiologic implications are considered.
authors.affiliation: British Columbia Centre for Disease Control (BCCDC), Vancouver, British Columbia, Canada. danuta.skowronski@bccdc.ca
authors.forename: Danuta M
authors.initials: DM
authors.lastname: Skowronski
authors.forename: Gaston
authors.initials: G
authors.lastname: De Serres
authors.forename: Natasha S
authors.initials: NS
authors.lastname: Crowcroft
authors.forename: Naveed Z
authors.initials: NZ
authors.lastname: Janjua
authors.forename: Nicole
authors.initials: N
authors.lastname: Boulianne
authors.forename: Travis S
authors.initials: TS
authors.lastname: Hottes
authors.forename: Laura C
authors.initials: LC
authors.lastname: Rosella
authors.forename: James A
authors.initials: JA
authors.lastname: Dickinson
authors.forename: Rodica
authors.initials: R
authors.lastname: Gilca
authors.forename: Pam
authors.initials: P
authors.lastname: Sethi
authors.forename: Najwa
authors.initials: N
authors.lastname: Ouhoummane
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Willison
authors.forename: Isabelle
authors.initials: I
authors.lastname: Rouleau
authors.forename: Martin
authors.initials: M
authors.lastname: Petric
authors.forename: Kevin
authors.initials: K
authors.lastname: Fonseca
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Drews
authors.forename: Anuradha
authors.initials: A
authors.lastname: Rebbapragada
authors.forename: Hugues
authors.initials: H
authors.lastname: Charest
authors.forename: Marie-Eve
authors.initials: ME
authors.lastname: Hamelin
authors.forename: Guy
authors.initials: G
authors.lastname: Boivin
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Gardy
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Trijntje L
authors.initials: TL
authors.lastname: Kwindt
authors.forename: David M
authors.initials: DM
authors.lastname: Patrick
authors.forename: Robert C
authors.initials: RC
authors.lastname: Brunham
mesh_terms: D002170:Canada / Q000453:epidemiology; D004196:Disease Outbreaks; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000472:pathogenicity*; D007252:Influenza Vaccines / Q000009:adverse effects*; D007251:Influenza, Human / Q000453:epidemiology* / Q000821:virology; D019370:Observation
chemical_list: D007252:Influenza Vaccines
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