Abstract

Data on influenza vaccine effectiveness (IVE) against mortality are limited, with no Australian data to guide vaccine uptake. We aimed to assess IVE against influenza-related mortality in Australian hospitalized patients, assess residual confounding in the association between influenza vaccination and mortality, and assess whether influenza vaccination reduces the severity of influenza illness. Data were collected between 2010 and 2017 from a national Australian hospital-based sentinel surveillance system using a case-control design. Adults and children admitted to the 17 study hospitals with acute respiratory symptoms were tested for influenza using nucleic acid testing; all eligible test-positive cases, and a subset of test-negative controls, were included. Propensity score analysis and multivariable logistic regression were used to determine the adjusted odds ratio (aOR) of vaccination, with IVE = 1 - aOR × 100%. Residual confounding was assessed by examining mortality in controls. Over 8 seasons, 14038 patients were admitted with laboratory-confirmed influenza. The primary analysis included 9298 cases and 6451 controls, with 194 cases and 136 controls dying during hospitalization. Vaccination was associated with a 31% (95% confidence interval [CI], 3%-51%; P = .033) reduction in influenza-related mortality, with similar estimates in the National Immunisation Program target group. Residual confounding was identified in patients ≥65 years old (aOR, 1.92 [95% CI, 1.06-3.46]; P = .031). There was no evidence that vaccination reduced the severity of influenza illness (aOR, 1.07 [95% CI, .76-1.50]; P = .713). Influenza vaccination is associated with a moderate reduction in influenza-related mortality. This finding reinforces the utility of the Australian vaccination program in protecting those most at risk of influenza-related deaths.

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