Influenza vaccine effectiveness against influenza-related hospitalization during a season with mixed outbreaks of four influenza viruses: a test-negative case-control study in adults in Canada

Abstract

Background: The Serious Outcomes Surveillance (SOS) Network was established to monitor seasonal influenza complications among hospitalized Canadian adults and to assess the effectiveness of influenza vaccination against severe outcomes. Here we report age- and strain-specific vaccine effectiveness (VE) in preventing severe outcomes during a season characterized by mixed outbreaks of four different influenza strains.

Methods: This prospective, multicentre, test-negative case-control study evaluated the VE of trivalent influenza vaccine (TIV) in the prevention of laboratory-confirmed influenza-hospitalization in adults aged ≥16 years (all adults) and adults aged 16-64 years (younger adults). The SOS Network identified hospitalized patients with diagnoses potentially attributable to influenza during the 2011/12 influenza season. Swabs collected at admission were tested by reverse transcriptase polymerase chain reaction (RT PCR) or viral culture to discriminate influenza cases (positive) from controls (negative). VE was calculated as 1-odds ratio (OR) of vaccination in cases versus controls × 100.

Results: Overall, in all adults, the unadjusted and adjusted VEs of TIV against influenza-hospitalization were 41.8% (95% Confidence Interval [CI]: 26.0, 54.3), and 42.8% (95% CI: 23.8, 57.0), respectively. In younger adults (16-64 years), the unadjusted and adjusted VEs of TIV against influenza-hospitalization were 35.8% (95% CI: 4.5, 56.8) and 33.2% (95% CI: -6.7, 58.2), respectively. In the all adults group, adjusted VE against influenza A/H1N1 was 72.5% (95% CI: 30.5, 89.1), against A/H3N2 was 86.1% (95% CI: 40.1, 96.8), against B/Victoria was 40.5% (95% CI: -28.9, 72.6), and against B/Yamagata was 32.3% (95% CI: -8.3, 57.7). The adjusted estimate of early season VE (from November 1 to March 11) was 54.4% (95% CI: 29.7-70.4), which was higher than late season (from March 11 to May 25) VE estimate (VE: 29.7%, 95% CI: -5.3, 53.1).

Conclusions: These results suggest that TIV was highly effective against A viruses and moderately effective against B viruses during a mild season characterised by co-circulation of four influenza strains in Canada. Findings underscore the need to provide VE assessment by subtype/lineage as well as the timing of vaccination (early season vs late season) to accurately evaluate vaccine performance and thus guide public health decision-making.

Trial registration: ClinicalTrials.gov Identifier: NCT01517191. Registration was retrospective and the date of registration was January 17, 2012.

Keywords: Adults; Effectiveness; Hospitalization; Influenza; Vaccine.

Conflict of interest statement

Ethics approval and consent to participate

The protocol was approved by the Research Ethics Boards of participating institutions. The full names of individual Research Ethics Boards for each SOS Network participating center are listed here: Halifax site: Capital Health Research Ethics Board; Mount Sinai and TIBDN sites: Mount Sinai Hospital Research Ethics Board; Hamilton site: Hamilton Health Sciences/ McMaster Health Sciences Research Ethics Board; Vancouver site: The University of British Columbia Clinical Research Ethics Board; Ottawa site: Ottawa Health Science Network Research Ethics Board; Quebec City site: Comité d’éthique de la recherché du CHU de Québec; Sherbrooke site: Comité d’éthique de la recherché sur l’human du Centre Hospitalier universitaire de Sherbrooke; Saint John site: Horizon Health Network Research Ethics Board; Montreal site: Montreal General Hospital BMD Research Ethics Committee; North York site: North York General Research Ethics Board; Toronto East site: Toronto East General Hospital Research Ethics Board; William Osler site (Brampton, On): William Osler Health System Research Ethics Board; Sudbury site: Health Sciences North Research Ethics Board. All patients provided written informed consent for data and sample collection, and medical record screening in accordance with the local Research Ethics Boards requirements.

Consent for publication

N/A

Competing interests

MKA reports grant funding from the GSK group of companies, Pfizer and Sanofi Pasteur. VS reports he was employed by GSK Vaccines at the time of the study and is now employed by Novavax Vaccines, and holds shares in the GSK group of companies. TH reports grant funding from the GSK group of companies, and payments from Pfizer and Abbvie, outside the submitted work. AA has nothing to disclose. GB has nothing to disclose. WB has nothing to disclose. AC reports payments from Sanofi, outside the submitted work. GDS reports he was external consultant at Business & Decision Life Sciences (on behalf of GSK) at the time of the study, and is currently employed by the GSK group of companies and holds shares in the GSK group of companies. ME has nothing to disclose. KG has nothing to disclose. FH reports he is employed by the GSK group of companies. SAH reports payments from the GSK group of companies, during the conduct of the study and outside the submitted work. BI reports she was employed by the GSK group of companies at the time of the study. JJ has nothing to disclose. KK has nothing to disclose. JML reports payments from the GSK group of companies and CIHR, during the conduct of the study; and reports payment from the GSK group of companies, outside the submitted work. JL has nothing to disclose. ML has nothing to disclose. DM-C has nothing to disclose. AMcC has nothing to disclose. JM reports payments to her institution from GlaxoSmithKline Group of Companies, and Sanofi Pasteur, outside of the submitted work. AMcG reports payments to her institution from the GSK group of companies for the conduct of this study, and payments from Hoffman La Roche and Sanofi Pasteur, outside the submitted work. MKN has nothing to disclose. JP reports payments from the GSK group of companies, Merck, Roche and Synthetic Biologics, outside the submitted work. DR has nothing to disclose. MS reports payments from the GSK group of companies and Pfizer, during the conduct of the study. GS has nothing to disclose. ST reports payments from CIHR, during the conduct of the study. LV reports payments from the GSK group of companies, during the conduct of the study. DW has nothing to disclose. LY has nothing to disclose. SAM reports payments from the GSK group of companies, during the conduct of the study; and reports payments from Pfizer, Merck, Novartis and Sanofi, outside the submitted work.

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Figures

Fig. 1

Laboratory-confirmed influenza cases and test-negative controls by week and virus subtype, November 1, 2011 to May 25, 2012