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 Previous estimates of 250 000-500 000 annual influenza deaths are outdated.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. FUNDING: None.

All India Institute of Medical Sciences New Delhi India

Centers for Disease Control and Prevention Kenya Nairobi Kenya

Centre for Respiratory Diseases and Meningitis National Institute for Communicable Diseases National Health Laboratory Service Johannesburg South Africa

Department for Infectious Disease Epidemiology Robert Koch Institute Berlin Germany

Department of Biostatistics and Bioinformatics Rollins School of Public Health Emory University Atlanta GA USA

Department of Biostatistics and Bioinformatics University of New South Wales Sydney NSW Australia

Department of Epidemiology National Health Institute Doutor Ricardo Jorge Lisbon Portugal

Department of Infectious Disease Epidemiology Statens Serum Institut Copenhagen Denmark

Department of Infectious Diseases Epidemiology Ministry of Health Singapore

Department of Infectious Diseases Epidemiology National Institute of Public Health Prague Czech Republic

Department of Virology Medical University of Vienna Vienna Austria

Infection Disease Prevention and Control Branch Public Health Agency Canada Ottawa ON Canada

Influenza Division Centers for Disease Control and Prevention Atlanta GA USA

International Health Policy Program Ministry of Public Health Nonthaburi Thailand

Key Laboratory of Surveillance and Early warning on Infectious Disease Division of Infectious Disease Chinese Center for Disease Control and Prevention Beijing China

National Institute for Public Health and the Environment Bilthoven Netherlands

Oslo Centre for Biostatistics and Epidemiology Oslo University Hospital and University of Oslo Norway; Domain for Infection Control and Environmental Health Norwegian Institute of Public Health Oslo Norway

Pan American Health Organization Washington DC USA

WHO Collaborating Centre for Infectious Disease Epidemiology and Control School of Public Health Li Ka Shing Faculty of Medicine The University of Hong Kong Hong Kong Special Administrative Region China

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WHO. [accessed May 10, 2016];Influenza (seasonal) fact sheet. 2016 http://www.who.int/mediacentre/factsheets/fs211/en/

UN Population Division. [accessed May 12, 2016];World population prospects. 2017 http://esa.un.org/unpd/wpp/Download/Standard/Population/

Simonsen L, Spreeuwenberg P, Lustig R, et al. Global mortality estimates for the 2009 influenza pandemic from the GLaMOR project: a modeling Study. PLoS Med. 2013;10:e1001558. PubMed PMC

Chow A, Ma S, Ling AE, Chew SK. Influenza-associated deaths in tropical Singapore. Emerg Infect Dis. 2006;12:114–21. PubMed PMC

Foppa IM, Hossain MM. Revised estimates of influenza-associated excess mortality, United States, 1995 through 2005. Emerg Themes Epidemiol. 2008;5:26. PubMed PMC

Gran JM, Kacelnik O, Grjibovski AM, Aavitsland P, Iversen BG. Counting pandemic deaths: comparing reported numbers of deaths from influenza A(H1N1)pdm09 with estimated excess mortality. Influenza Other Respir Viruses. 2013;7:1370–79. PubMed PMC

Green HK, Andrews N, Fleming D, Zambon M, Pebody R. Mortality attributable to influenza in England and Wales prior to, during and after the 2009 pandemic. PLoS One. 2013;8:e79360. PubMed PMC

Kuo HW, Schmid D, Liu YL, Lachner P, Allerberger F. Influenza-related excess mortality, Austria 2001 till 2009. Wein Klin Wochenschr. 2011;123:593–98. PubMed

Kyncl J, Prochazka B, Goddard NL, et al. A study of excess mortality during influenza epidemics in the Czech Republic, 1982–2000. Eur J Epidemiol. 2005;20:365–71. PubMed

Lee VJ, Yap J, Ong JB, et al. Influenza excess mortality from 1950–2000 in tropical Singapore. PLoS One. 2009;4:e8096. PubMed PMC

Lemaitre M, Carrat F, Rey G, Miller M, Simonsen L, Viboud C. Mortality burden of the 2009 A/H1N1 influenza pandemic in France: comparison to seasonal influenza and the A/H3N2 pandemic. PLoS One. 2012;7:e45051. PubMed PMC

Linhart Y, Shohat T, Bromberg M, Mendelson E, Dictiar R, Green MS. Excess mortality from seasonal influenza is negligible below the age of 50 in Israel: implications for vaccine policy. Infection. 2011;39:399–404. PubMed PMC

Lopez-Cuadrado T, de Mateo S, Jimenez-Jorge S, Savulescu C, Larrauri A. Influenza-related mortality in Spain, 1999–2005. Gac Sanit. 2012;26:325–29. PubMed

Muscatello DJ, Newall AT, Dwyer DE, Macintyre CR. Mortality attributable to seasonal and pandemic influenza, Australia, 2003 to 2009, using a novel time series smoothing approach. PLoS One. 2014;8:e64734. PubMed PMC

Nunes B, Viboud C, Machado A, et al. Excess mortality associated with influenza epidemics in Portugal, 1980 to 2004. PLoS One. 2011;6:e20661. PubMed PMC

Rizzo C, Bella A, Viboud C, et al. Trends for influenza-related deaths during pandemic and epidemic seasons, Italy, 1969–2001. Emerg Infect Dis. 2007;13:694–99. PubMed PMC

Schanzer DL, Sevenhuysen C, Winchester B, Mersereau T. Estimating influenza deaths in Canada, 1992–2009. PLoS One. 2013;8:e80481. PubMed PMC

Wu P, Goldstein E, Ho LM, et al. Excess mortality associated with influenza A and B virus in Hong Kong, 1998–2009. J Infect Dis. 2012;206:1862–71. PubMed PMC

Zucs P, Buchholz U, Haas W, Uphoff H. Influenza associated excess mortality in Germany, 1985–2001. Emerg Themes Epidemiol. 2005;2:6. PubMed PMC

Estimates of deaths associated with seasonal influenza—United States, 1976–2007. MMWR Morb Mortal Wkly Rep. 2010;59:1057–62. PubMed

Freitas FT, Souza LR, Azziz-Baumgartner E, et al. Influenza-associated excess mortality in southern Brazil, 1980–2008. Epidemiol Infect. 2013;141:1731–40. PubMed PMC

Redlberger-Fritz M, Aberle JH, Popow-Kraupp T, Kundi M. Attributable deaths due to influenza: a comparative study of seasonal and pandemic influenza. Eur J Epidemiol. 2012;27:567–75. PubMed

Nielsen J, Mazick A, Glismann S, Molbak K. Excess mortality related to seasonal influenza and extreme temperatures in Denmark, 1994–2010. BMC Infect Dis. 2011;11:350. PubMed PMC

Wijngaard CC, Asten L, Koopmans MP, et al. Comparing pandemic to seasonal influenza mortality: moderate impact overall but high mortality in young children. PLoS One. 2012;7:e31197. PubMed PMC

Park M, Wu P, Goldstein E, Joo Kim W, Cowling BJ. Influenza-associated excess mortality in South Korea. Am J Prev Med. 2016;50:e111–19. PubMed PMC

Cohen C, Walaza S, Treurnicht FK, et al. In- and out-of-hospital mortality associated with seasonal and pandemic influenza and respiratory syncytial virus in South Africa, 2009–2013. Clin Infect Dis. 2017 doi: 10.1093/cid/cix740. published online Oct 10. PubMed DOI PMC

Polansky LS, Outin-Blenman S, Moen AC. Improved global capacity for influenza surveillance. Emerg Infect Dis. 2016;22:993–1001. PubMed PMC

Aungkulanon S, Cheng P-Y, Kusreesakul K, et al. Influenza-associated mortality in Thailand, 2006–2011. Influenza Other Respir Viruses. 2015;9:298–304. PubMed PMC

Cheng PY, Palekar R, Azziz-Baumgartner E, et al. Burden of influenza-associated deaths in the Americas, 2002–2008. Influenza Other Respir Viruses. 2015;9(suppl 1):13–21. PubMed PMC

Tempia S, Walaza S, Viboud C, et al. Deaths associated with respiratory syncytial and influenza viruses among persons ≥5 years of age in HIV-prevalent area, South Africa, 1998–2009. Emerg Infect Dis. 2015;21:600–08. PubMed PMC

Feng L, Shay DK, Jiang Y, et al. Influenza-associated mortality in temperate and subtropical Chinese cities, 2003–2008. Bull World Health Organ. 2012;90:279–88b. PubMed PMC

Goldstein E, Viboud C, Charu V, Lipsitch M. Improving the estimation of influenza-related mortality over a seasonal baseline. Epidemiology. 2012;23:829–38. PubMed PMC

Serfling RE. Methods for current statistical analysis of excess pneumonia-influenza deaths. Public Health Rep. 1963;78:494–506. PubMed PMC

Simonsen L, Clarke MJ, Stroup DF, Williamson GD, Arden NH, Cox NJ. A method for timely assessment of influenza-associated mortality in the United States. Epidemiology. 1997;8:390–95. PubMed

Thompson WW, Weintraub E, Dhankhar P, et al. Estimates of US influenza-associated deaths made using four different methods. Influenza Other Respir Viruses. 2009;3:37–49. PubMed PMC

Nicoll A, Ciancio BC, Lopez Chavarrias V, et al. Influenza-related deaths—available methods for estimating numbers and detecting patterns for seasonal and pandemic influenza in Europe. Euro Surveill. 2012;17:20162. PubMed

Nicholson KG, Wood JM, Zambon M. Influenza. Lancet. 2003;362:1733–45. PubMed PMC

Mathers CD, Fat DM, Inoue M, Rao C, Lopez AD. Counting the dead and what they died from: an assessment of the global status of cause of death data. Bull World Health Organ. 2005;83:171–77. PubMed PMC

Muscatello DJ, Amin J, MacIntyre CR, et al. Inaccurate ascertainment of morbidity and mortality due to influenza in administrative databases: a population-based record linkage study. PLoS One. 2014;9:e98446. PubMed PMC

Thompson WW, Shay DK, Weintraub E, et al. Mortality associated with influenza and respiratory syncytial virus in the United States. JAMA. 2003;289:179–86. PubMed

Simonsen L, Clarke MJ, Williamson GD, Stroup DF, Arden NH, Schonberger LB. The impact of influenza epidemics on mortality: introducing a severity index. Am J Public Health. 1997;87:1944–50. PubMed PMC

Katz MA, Schoub BD, Heraud JM, Breiman RF, Njenga MK, Widdowson M-A. Influenza in Africa: uncovering the epidemiology of a long-overlooked disease. J Infect Dis. 2012;206(suppl 1):S1–4. PubMed

Johnson LEA, Muir-Paulik SA, Kennedy P, et al. Capacity building in national influenza laboratories—use of laboratory assessments to drive progress. BMC Infect Dis. 2015;15:501. PubMed PMC

The GATHER Working Group. [accessed April 10, 2017];Guidelines for accurate and transparent health estimates reporting. 2016 http://gather-statement.org/

Stevens GA, Alkema L, Black RE, et al. Guidelines for accurate and transparent health estimates reporting: the GATHER statement. Lancet. 2016;388:e19–23. PubMed

United States Census Bureau. International programs. [accessed May 12, 2016];International data base. http://www.census.gov/population/international/data/idb/informationGateway.php.

WHO. Estimates for 2000–2015. [accessed Feb 22, 2017];Cause specific mortality. 2017 http://www.who.int/healthinfo/global_burden_disease/estimates/en/index1.html.

Centers for Disease Control and Prevention. [accessed March 3, 2012];Classification of Diseases and Injuries. (9). ftp://ftp.cdc.gov/pub/Health_Statistics/NCHS/Publications/ICD-9/ucod.txt.

WHO. [accessed March 3, 2012];International statistical classification of diseases and related health problems. 2011 10th revision. http://www.who.int/classifications/icd/ICD10Volume2_en_2010.pdf.

WHO. [accessed Feb 22, 2017];WHO methods and data sources for country-level causes of death 2000–2015. 2017 http://www.who.int/healthinfo/global_burden_disease/GlobalCOD_method_2000_2015.pdf?ua=1.

Dawood FS, Iuliano AD, Reed C, et al. Estimated global mortality associated with the first 12 months of 2009 pandemic influenza A H1N1 virus circulation: a modelling study. Lancet Infect Dis. 2012;12:687–95. PubMed

The World Bank. [accessed April 3, 2015];World Bank country and lending Groups. 2015 https://datahelpdesk.worldbank.org/knowledgebase/articles/906519-world-bank-country-and-lending-groups.

GBD 2015 Mortality and Causes of Death Collaborators. Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980–2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet. 2016;388:1459–544. PubMed PMC

Douglas RG., Jr Influenza: the disease and its complications. Hosp Pract. 1976;11:43–50. PubMed

Thompson WW, Comanor L, Shay DK. Epidemiology of seasonal influenza: use of surveillance data and statistical models to estimate the burden of disease. J Infect Dis. 2006;194(suppl 2):S82–91. PubMed

Nair H, Brooks WA, Katz M, et al. Global burden of respiratory infections due to seasonal influenza in young children: a systematic review and meta-analysis. Lancet. 2011;378:1917–30. PubMed

Wong KK, Jain S, Blanton L, et al. Influenza-associated pediatric deaths in the United States, 2004–2012. Pediatrics. 2013;132:796–804. PubMed PMC

WHO. [accessed April 1, 2015];Influenza transmission zones. 2011 http://www.who.int/csr/disease/swineflu/Influenza_transmission_zones.pdf?ua=1.

UN Statistics Division. [accessed April 1, 2015];Millennium development indicators: world and regional groupings. 2014 http://mdgs.un.org/unsd/mdg/Host.aspx?Content=Data/RegionalGroupings.htm.

UNICEF. [accessed April 1, 2015];Where we work. https://www.unicef.org/where-we-work.

Fleming DM. The contribution of influenza to combined acute respiratory infections, hospital admissions, and deaths in winter. Commun Dis Public Health. 2000;3:32–38. PubMed

Fleming DM, Cross KW, Pannell RS. Influenza and its relationship to circulatory disorders. Epidemiol Infect. 2005;133:255–62. PubMed PMC

Reichert TA, Simonsen L, Sharma A, Pardo SA, Fedson DS, Miller MA. Influenza and the winter increase in mortality in the United States, 1959–1999. Am J Epidemiol. 2004;160:492–502. PubMed

Simonsen L, Clarke MJ, Williamson GD, Stroup DF, Arden NH, Schonberger LB. The impact of influenza epidemics on mortality: introducing a severity index. Am J Public Health. 1997;87:1944–50. PubMed PMC

Collins SD. Excess mortality from causes other than influenza and pneumonia during influenza epidemics. Public Health Rep. 1932;47:2159–79. PubMed

Warren-Gash C, Bhaskaran K, Hayward A, et al. Circulating influenza virus, climatic factors, and acute myocardial infarction: a time series study in England and Wales and Hong Kong. J Infect Dis. 2011;203:1710–18. PubMed PMC

Kostova D, Reed C, Finelli L, et al. Influenza illness and hospitalizations averted by influenza vaccination in the United States, 2005–2011. PLoS One. 2013;8:e66312. PubMed PMC

Vaccines against influenza WHO position paper—November 2012. Wkly Epidemiol Rec. 2012;87:461–76. No authors listed. PubMed

Predictors of Severity of Influenza-Related Hospitalizations: Results From the Global Influenza Hospital Surveillance Network (GIHSN)

Amphiphilic Sialic Acid Derivatives as Potential Dual-Specific Inhibitors of Influenza Hemagglutinin and Neuraminidase

Synthesis and In Vitro Evaluation of C-7 and C-8 Luteolin Derivatives as Influenza Endonuclease Inhibitors

Recommendations for vaccination in multiple myeloma: a consensus of the European Myeloma Network

Complicated hospitalization due to influenza: results from the Global Hospital Influenza Network for the 2017-2018 season

Determinants of Fatal Outcome in Patients Admitted to Intensive Care Units With Influenza, European Union 2009-2017

Neutrophils-related host factors associated with severe disease and fatality in patients with influenza infection

DNA-linked inhibitor antibody assay (DIANA) as a new method for screening influenza neuraminidase inhibitors