www.thelancet.com/infection Published online June 26, 2012 http://dx.doi.org/10.1016/S1473-3099(12)70121-4 1 Articles Published Online June 26, 2012 http://dx.doi.org/10.1016/ S1473-3099(12)70121-4 See Online/Comment http://dx.doi.org/10.1016/ S1473-3099(12)70152-4 Influenza Division, Centers for Disease Control and Prevention, Atlanta, GA, USA (F S Dawood MD, A D Iuliano PhD, C Reed DSc, D K Shay MD, P-Y Cheng PhD, R Lal PhD, J M Montgomery PhD, J Bresee MD, M-A Widdowson VetMB); Scientific and Program Services Branch, Division of Preparedness and Emerging Infections, Centers for Disease Control and Prevention, Atlanta, GA, USA (M I Meltzer PhD); National Centre for Biosecurity and Infectious Disease, Environmental Science and Research Institute, Upper Hutt, New Zealand (D Bandaranayake MBBS, Q S Huang PhD); Global Disease Detection Division, Kenya Medical Research Institute/Centers for Disease Control and Prevention, Nairobi, Kenya (R F Breiman MD, D R Feikin MD, M A Katz MD); International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh (W A Brooks MD); Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA (W A Brooks); National Influenza Center, Phnom Penh, Cambodia (P Buchy MD); University of Alabama, Birmingham, AL, USA (K B Fowler DrPH); University of California, Berkeley, CA, USA (A Gordon PhD); John E Fogarty International Center, National Institutes of Health, Bethesda, MD, USA (A Gordon); National Institute for Hygiene and Epidemiology, Hanoi, Vietnam Estimated global mortality associated with the first 12 months of 2009 pandemic influenza A H1N1 virus circulation: a modelling study Fatimah S Dawood, A Danielle Iuliano, Carrie Reed, Martin I Meltzer, David K Shay, Po-Yung Cheng, Don Bandaranayake, Robert F Breiman, W Abdullah Brooks, Philippe Buchy, Daniel R Feikin, Karen B Fowler, Aubree Gordon, Nguyen Tran Hien, Peter Horby, Q Sue Huang, Mark A Katz, Anand Krishnan, Renu Lal, Joel M Montgomery, Kåre Mølbak, Richard Pebody, Anne M Presanis, Hugo Razuri, Anneke Steens, Yeny O Tinoco, Jacco Wallinga, Hongjie Yu, Sirenda Vong, Joseph Bresee, Marc-Alain Widdowson Summary Background 18 500 laboratory-conirmed deaths caused by the 2009 pandemic inluenza A H1N1 were reported worldwide for the period April, 2009, to August, 2010. This number is likely to be only a fraction of the true number of the deaths associated with 2009 pandemic inluenza A H1N1. We aimed to estimate the global number of deaths during the irst 12 months of virus circulation in each country. Methods We calculated crude respiratory mortality rates associated with the 2009 pandemic inluenza A H1N1 strain by age (0–17 years, 18–64 years, and >64 years) using the cumulative (12 months) virus-associated symptomatic attack rates from 12 countries and symptomatic case fatality ratios (sCFR) from ive high-income countries. To adjust crude mortality rates for diferences between countries in risk of death from inluenza, we developed a respiratory mortality multiplier equal to the ratio of the median lower respiratory tract infection mortality rate in each WHO region mortality stratum to the median in countries with very low mortality. We calculated cardiovascular disease mortality rates associated with 2009 pandemic inluenza A H1N1 infection with the ratio of excess deaths from cardiovascular and respiratory diseases during the pandemic in ive countries and multiplied these values by the crude respiratory disease mortality rate associated with the virus. Respiratory and cardiovascular mortality rates associated with 2009 pandemic inluenza A H1N1 were multiplied by age to calculate the number of associated deaths. Findings We estimate that globally there were 201 200 respiratory deaths (range 105 700–395 600) with an additional 83 300 cardiovascular deaths (46 000–179 900) associated with 2009 pandemic inluenza A H1N1. 80% of the respiratory and cardiovascular deaths were in people younger than 65 years and 59% occurred in southeast Asia and Africa. Interpretation Our estimate of respiratory and cardiovascular mortality associated with the 2009 pandemic inluenza A H1N1 was 15 times higher than reported laboratory-conirmed deaths. Although no estimates of sCFRs were available from Africa and southeast Asia, a disproportionate number of estimated pandemic deaths might have occurred in these regions. Therefore, eforts to prevent inluenza need to efectively target these regions in future pandemics. Funding None. Introduction Inluenza pandemics are typically characterised by higher, but widely varying, number of deaths than are seasonal epidemics. 1 The emergence of pandemic inluenza A H1N1 in April, 2009, led WHO to request that countries report all laboratory-conirmed deaths associated with it. For the period up to August, 2010, 18 500 deaths associated with laboratory-conirmed 2009 pandemic inluenza A H1N1 have been reported. 2 This number is likely to be an underestimate because diagnostic specimens are not always obtained from people who die with inluenza and the viruses might no longer be detectable by the time of death in some people. Estimation of the 2009-pandemic-associated mortality presents several challenges. First, data for inluenza in many countries are sparse and obtained through virological surveillance without standardised case re- porting or population denominators needed to estimate incidence. Second, the level and timing of the circulation of the pandemic virus might vary by region and country. 3–5 Third, the severity of inluenza might vary by region and country due to diferences in access to and quality of health care, nutritional status, prevalence of underlying chronic disorders, age distribution of the populations, and the use of inluenza vaccines and antiviral drugs. 6–10 Inluenza-associated mortality is often estimated indirectly, by use of statistical models, as the number of excess deaths during periods of circulation of the virus. 11–13 Inluenza-associated deaths that might be missed by direct counts of only laboratory-conirmed deaths are taken into account with the use of these indirect approaches. However, indirect estimation might not be