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To access, purchase, authenticate, or subscribe to the full-text of this article, please visit this link: http://dx.doi.org/10.1016/S0140-6736(17)33293-2 Byline: A Danielle Iuliano, PhD [aiuliano@cdc.gov] (a,*), Katherine M Roguski, MPH (a), Howard H Chang, PhD (b), David J Muscatello, PhD (c), Rakhee Palekar, MD (d), Stefano Tempia, PhD (a), Cheryl Cohen, PhD (e), Jon Michael Gran, PhD (f,g), Dena Schanzer, MSc (h), Prof Benjamin J Cowling, PhD (i), Peng Wu, PhD (i), Jan Kyncl, MD (j), Li Wei Ang, MSc (k), Minah Park, MPH (i), Monika Redlberger-Fritz, MD (l), Hongjie Yu, MD (m), Laura Espenhain, MPHS (n), Prof Anand Krishnan, PhD (o), Gideon Emukule, PhD (p), Liselotte van Asten, PhD (q), Susana Pereira da Silva, MSc (r), Suchunya Aungkulanon, MSc (s), Udo Buchholz, MD (t), Marc-Alain Widdowson, VetMB (p), Joseph S Bresee, MD (a), Eduardo Azziz-Baumgartner, Po-Yung Cheng, Fatimah Dawood, Ivo Foppa, Sonja Olsen, Michael Haber, Caprichia Jeffers, C Raina MacIntyre, Anthony T Newall, James G Wood, Michael Kundi, Therese Popow-Kraupp, Makhdum Ahmed, Mahmudur Rahman, Fatima Marinho, C Viviana Sotomayor Proschle, Natalia Vergara Mallegas, Feng Luzhao, Li Sa, Juliana Barbosa-Ramirez, Diana Malo Sanchez, Leandra Abarca Gomez, Xiomara Badilla Vargas, aBetsy Acosta Herrera, Maria Josefa Llanes, Thea Kolsen Fischer, Tyra Grove Krause, Kare Molbak, Jens Nielsen, Ramona Trebbien, Alfredo Bruno, Jenny Ojeda, Hector Ramos, Matthias an der Heiden, Leticia del Carmen Castillo Signor, Carlos Enrique Serrano, Rohit Bhardwaj, Mandeep Chadha, Venkatesh Narayan, Soewarta Kosen, Michal Bromberg, Aharona Glatman-Freedman, Zalman Kaufman, Yuzo Arima, Kazunori Oishi, Sandra Chaves, Bryan Nyawanda, Reem Abdullah Al-Jarallah, Pablo A Kuri-Morales, Cuitlahuac Ruiz Matus, Maria Eugenia Jimenez Corona, Alexander Burmaa, Oyungerel Darmaa, Majdouline Obtel, Imad Cherkaoui, Cees C van den Wijngaard, Wim van der Hoek, Michael Baker, Don Bandaranayake, Ange Bissielo, Sue Huang, Liza Lopez, Claire Newbern, Elmira Flem, Gry M Groneng, Siri Hauge, Federico G de Cosio, Yadira de Molto, Lourdes Moreno Castillo, Maria Agueda Cabello, Marta von Horoch, Jose Medina Osis, Ausenda Machado, Baltazar Nunes, Ana Paula Rodrigues, Emanuel Rodrigues, Cristian Calomfirescu, Emilia Lupulescu, Rodica Popescu, Odette Popovici, Dragan Bogdanovic, Marina Kostic, Konstansa Lazarevic, Zoran Milosevic, Branislav Tiodorovic, Mark Chen, Jeffery Cutter, Vernon Lee, Raymond Lin, Stefan Ma, Adam L Cohen, Florette Treurnicht, Woo Joo Kim, Concha Delgado-Sanz, Salvador de mateo Ontanon, Amparo Larrauri, Inmaculada Leon Leon, Fernando Vallejo, Rita Born, Christoph Junker, Daniel Koch, Jen-Hsiang Chuang, Wan-Ting Huang, Hung-Wei Kuo, Yi-Chen Tsai, Kanitta Bundhamcharoen, Malinee Chittaganpitch, Helen K Green, Richard Pebody, Natalia Goni, Hector Chiparelli, Lynnette Brammer, Desiree Mustaquim Summary 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 ( 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. Author Affiliation: (a) Influenza Division, Centers for Disease Control and Prevention, Atlanta, GA, USA (b) Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA, USA (c) Department of Biostatistics and Bioinformatics, University of New South Wales, Sydney, NSW, Australia (d) Pan American Health Organization, Washington, DC, USA (e) Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases, National Health Laboratory Service, Johannesburg, South Africa (f) Oslo Centre for Biostatistics and Epidemiology, Oslo University Hospital and University of Oslo, Norway (g) Domain for Infection Control and Environmental Health, Norwegian Institute of Public Health, Oslo, Norway (h) Infection Disease Prevention and Control Branch, Public Health Agency Canada, Ottawa, ON, Canada (i) 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 (j) Department of Infectious Diseases Epidemiology, National Institute of Public Health, Prague, Czech Republic (k) Department of Infectious Diseases Epidemiology, Ministry of Health, Singapore (l) Department of Virology, Medical University of Vienna, Vienna, Austria (m) Key Laboratory of Surveillance and Early-warning on Infectious Disease, Division of Infectious Disease, Chinese Center for Disease Control and Prevention, Beijing, China (n) Department of Infectious Disease Epidemiology, Statens Serum Institut, Copenhagen, Denmark (o) All India Institute of Medical Sciences, New Delhi, India (p) Centers for Disease Control and Prevention-Kenya, Nairobi, Kenya (q) National Institute for Public Health and the Environment, Bilthoven, Netherlands (r) Department of Epidemiology, National Health Institute Doutor Ricardo Jorge, Lisbon, Portugal (s) International Health Policy Program, Ministry of Public Health, Nonthaburi, Thailand (t) Department for Infectious Disease Epidemiology, Robert Koch-Institute, Berlin, Germany * Correspondence to: Dr A Danielle Iuliano, Influenza Division, Centers for Disease Control and Prevention, Atlanta, GA 30329-4027, USA (footnote)[Dagger] Members of the Global Seasonal Influenza-associated Mortality Collaborator Network are listed in the