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

Global Seasonal Influenza-associated Mortality Collaborator Network: Portugal: Susana Pereira da Silva, Emanuel Rodrigues, Baltazar Nunes, Ana Paula Rodrigues, Ausenda Machado (Epidemiology Department, National Health Institute Doutor Ricardo Jorge).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 ~ 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.This study was supported by the WHO on a contract with NIVEL (APW 201497873) and the MISMS influenza program led by in-house research division of the Fogarty International Center of the US NIHinfo:eu-repo/semantics/publishedVersio

Estimates of global seasonal influenza-associated respiratory mortality: a modelling study

BACKGROUND: Estimates of influenza-associated mortality are important for national and international decision making on public health priorities. Previous estimates of 250 000-500 000 annual influenza deaths are outdated. We updated the estimated number of global annual influenza-associated respiratory deaths using country-specific influenza-associated excess respiratory mortality estimates from 1999-2015. METHODS: We estimated country-specific influenza-associated respiratory excess mortality rates (EMR) for 33 countries using time series log-linear regression models with vital death records and influenza surveillance data. To extrapolate estimates to countries without data, we divided countries into three analytic divisions for three age groups (<65 years, 65-74 years, and ≥75 years) using WHO Global Health Estimate (GHE) respiratory infection mortality rates. We calculated mortality rate ratios (MRR) to account for differences in risk of influenza death across countries by comparing GHE respiratory infection mortality rates from countries without EMR estimates with those with estimates. To calculate death estimates for individual countries within each age-specific analytic division, we multiplied randomly selected mean annual EMRs by the country's MRR and population. Global 95% credible interval (CrI) estimates were obtained from the posterior distribution of the sum of country-specific estimates to represent the range of possible influenza-associated deaths in a season or year. We calculated influenza-associated deaths for children younger than 5 years for 92 countries with high rates of mortality due to respiratory infection using the same methods. FINDINGS: EMR-contributing countries represented 57% of the global population. The estimated mean annual influenza-associated respiratory EMR ranged from 0·1 to 6·4 per 100 000 individuals for people younger than 65 years, 2·9 to 44·0 per 100 000 individuals for people aged between 65 and 74 years, and 17·9 to 223·5 per 100 000 for people older than 75 years. We estimated that 291 243-645 832 seasonal influenza-associated respiratory deaths (4·0-8·8 per 100 000 individuals) occur annually. The highest mortality rates were estimated in sub-Saharan Africa (2·8-16·5 per 100 000 individuals), southeast Asia (3·5-9·2 per 100 000 individuals), and among people aged 75 years or older (51·3-99·4 per 100 000 individuals). For 92 countries, we estimated that among children younger than 5 years, 9243-105 690 influenza-associated respiratory deaths occur annually. INTERPRETATION: These global influenza-associated respiratory mortality estimates are higher than previously reported, suggesting that previous estimates might have underestimated disease burden. The contribution of non-respiratory causes of death to global influenza-associated mortality should be investigated.info:eu-repo/semantics/publishedVersio