Association between the 2008-09 Seasonal Influenza Vaccine and Pandemic H1N1 Illness during Spring-Summer 2009: Four Observational Studies from Canada

作者：Skowronski Danuta M^*; De Serres Gaston; Crowcroft Natasha S; Janjua Naveed Z; Boulianne Nicole; Hottes Travis S; Rosella Laura C; Dickinson James A; Gilca Rodica; Sethi Pam; Ouhoummane Najwa; Willison Donald J; Rouleau Isabelle; Petric Martin; Fonseca Kevin; Drews Steven J; Rebbapragada Anuradha; Charest Hugues; Hamelin Marie Eve; Boivin Guy; Gardy Jennifer L; Li Yan; Kwindt Trijntje L; Patrick David M; Brunham Robert C

来源：PLoS Medicine, 2010, 7(4): e1000258.

DOI：10.1371/journal.pmed.1000258

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.
Methods and Findings: Studies included: (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.

• 出版日期2010-4