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.

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.