Existing methods for estimation of mortality attributable to influenza are limited by methodological and data uncertainty. We have used proxies for disease incidence of the three influenza cocirculating subtypes (A/H3N2, A/H1N1, and B) that combine data on influenza-like illness consultations and respiratory specimen testing to estimate influenza-associated mortality in the United States between 1997 and 2007.
Weekly mortality rate for several mortality causes potentially affected by influenza was regressed linearly against subtype-specific influenza incidence proxies, adjusting for temporal trend and seasonal baseline, modeled by periodic cubic splines.
Average annual influenza-associated mortality rates per 100,000 individuals were estimated for the following underlying causes of death: for pneumonia and influenza, 1.73 (95% confidence interval = 1.53–1.93); for chronic lower respiratory disease, 1.70 (1.48–1.93); for all respiratory causes, 3.58 (3.04–4.14); for myocardial infarctions, 1.02 (0.85–1.2); for ischemic heart disease, 2.7 (2.23–3.16); for heart disease, 3.82 (3.21–4.4); for cerebrovascular deaths, 0.65 (0.51–0.78); for all circulatory causes, 4.6 (3.79–5.39); for cancer, 0.87 (0.68–1.05); for diabetes, 0.33 (0.26–0.39); for renal disease, 0.19 (0.14–0.24); for Alzheimer disease, 0.41 (0.3–0.52); and for all causes, 11.92 (10.17–13.67). For several underlying causes of death, baseline mortality rates changed after the introduction of the pneumococcal conjugate vaccine.
The proposed methodology establishes a linear relation between influenza incidence proxies and excess mortality, rendering temporally consistent model fits, and allowing for the assessment of related epidemiologic phenomena such as changes in mortality baselines.
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From the aDepartment of Epidemiology, Center for Communicable Disease Dynamics, Harvard School of Public Health, Boston, MA; bDivision of International Epidemiology and Population Studies, Fogarty International Center, National Institutes of Health, Bethesda, MD; cSchool of Medicine, Johns Hopkins University, Baltimore, MD; and dDepartment of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA.
Submitted 7 November, 2011; accepted 22 March, 2012; posted 18 September 2012.
Supported, in part, by the US National Institutes of Health Models of Infectious Disease Agent Study program through cooperative agreement 1 U54 GM088558 (M.L., E.G.), by the US National Institutes of Health K01 award 1K01AI101010-01 (E.G.), and by the influenza research program of the Fogarty International Center, US NIH (C.V., V.C.).
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Editors’ note: Related articles appear on pages 839 and 843.
Correspondence: Edward Goldstein, Harvard School of Public Health, Department of Epidemiology, 677 Huntington Ave, Kresge Room 506, Boston, MA 02115. E-mail: email@example.com.