Global mortality associated with seasonal influenza epidemics: New burden estimates and predictors from the GLaMOR Project

Background Until recently, the World Health Organization (WHO) estimated the annual mortality burden of influenza to be 250 000 to 500 000 all-cause deaths globally; however, a 2017 study indicated a substantially higher mortality burden, at 290 000-650 000 influenza-associated deaths from respiratory causes alone, and a 2019 study estimated 99 000-200 000 deaths from lower respiratory tract infections directly caused by influenza. Here we revisit global and regional estimates of influenza mortality burden and explore mortality trends over time and geography. Methods We compiled influenza-associated excess respiratory mortality estimates for 31 countries representing 5 WHO regions during 2002-2011. From these we extrapolated the influenza burden for all 193 countries of the world using a multiple imputation approach. We then used mixed linear regression models to identify factors associated with high seasonal influenza mortality burden, including influenza types and subtypes, health care and socio-demographic development indicators, and baseline mortality levels. Results We estimated an average of 389 000 (uncertainty range 294 000-518 000) respiratory deaths were associated with influenza globally each year during the study period, corresponding to similar to 2% of all annual respiratory deaths. Of these, 67% were among people 65 years and older. Global burden estimates were robust to the choice of countries included in the extrapolation model. For people <65 years, higher baseline respiratory mortality, lower level of access to health care and seasons dominated by the A(H1N1)pdm09 subtype were associated with higher influenza-associated mortality, while lower level of socio-demographic development and A(H3N2) dominance was associated with higher influenza mortality in adults >= 65 years. Conclusions Our global estimate of influenza-associated excess respiratory mortality is consistent with the 2017 estimate, despite a different modelling strategy, and the lower 2019 estimate which only captured deaths directly caused by influenza. Our finding that baseline respiratory mortality and access to health care are associated with influenza-related mortality in persons <65 years suggests that health care improvements in low and middle-income countries might substantially reduce seasonal influenza mortality. Our estimates add to the body of evidence on the variation in influenza burden over time and geography, and begin to address the relationship between influenza-associated mortality, health and development.