A systematic review of studies of influenza-associated mortality

Abstract

BACKGROUND: Influenza viruses are associated with a substantial global burden of morbidity and mortality every year. Reliable estimation of influenza associated disease burden sometimes can be difficult, and estimates of disease burden often vary between studies conducted in various settings and applying different methods and outcome measurements. We reviewed published studies which assessed the influenza-associated mortality burden. METHOD: We searched PubMed and Embase for articles evaluating the influenza-attributed mortality burden. Eligible articles were those that presented estimates of influenza-associated mortality at a population level. Gross domestic product (GDP) of each countries was obtained from the World Economic Outlook Database. A meta-regression was used to examine the impact of moderator variables on the estimate of mortality burden attributable to influenza. RESULTS: We identified 103 eligible articles for inclusion. The majority of studies were published within the past 10 years. Statistical methods used in the included studies could be classified into 2 groups, which were multiplier methods, and assessments of excess deaths from ecological data. Methods used in identified articles varied considerably. Estimates of excess mortality increased with age, and increased for broader cause of death classifications. Mortality burden was higher in countries of low GDP level after accounting for age differences with countries of high GDP level. In the meta-regression analysis, the Serfling-type model tended to give higher estimates and the estimate for 2009 pandemic influenza was lower than that for seasonal influenza. CONCLUSION: We identified important methodological differences in published studies, which did affect estimates of influenza-associated mortality. Standardization of methodology would permit more accurate comparisons of the estimates of mortality burden attributable to influenza. The impact of influenza may be greater in countries of low GDP level, after differences in age structure are taken into account. Mortality burden caused by seasonal influenza was higher than that caused by the 2009 pandemic influenza.