Lone Simonsen, PhD; Thomas A. Reichert, MD, PhD; Cecile Viboud, PhD; William C. Blackwelder, PhD; Robert J. Taylor, PhD; Mark A. Miller, MD. Impact of influenza vaccination on Seasonal Mortality in the US Elderly Population. Arch Intern Med. 2005;165:265-272.

Author Affiliations: National Institute of allergy and Infectious Diseases (NIAID) (Dr Simonsen) and Fogarty International Center (Drs Viboud and Miller), National Institutes of health, Bethesda, Md; and Entropy Research Institute, Boston, Mass (Dr Reichert).

Background Observational studies report that influenza vaccination reduces winter mortality risk from any cause by 50% among the elderly. influenza vaccination coverage among elderly persons (e65 years) in the United States increased from between 15% and 20% before 1980 to 65% in 2001. Unexpectedly, estimates of influenza-related mortality in this age group also increased during this period. We tried to reconcile these conflicting findings by adjusting excess mortality estimates for aging and increased circulation of influenza A(H3N2) viruses.

Methods We used a cyclical regression model to generate seasonal estimates of national influenza-related mortality (excess mortality) among the elderly in both pneumonia and influenza and all-cause deaths for the 33 seasons from 1968 to 2001. We stratified the data by 5-year age group and separated seasons dominated by A(H3N2) viruses from other seasons.

Results For people aged 65 to 74 years, excess mortality rates in A(H3N2)-dominated seasons fell between 1968 and the early 1980s but remained approximately constant thereafter. For persons 85 years or older, the mortality rate remained flat throughout. Excess mortality in A(H1N1) and B seasons did not change. All-cause excess mortality for persons 65 years or older never exceeded 10% of all winter deaths.

Conclusions We attribute the decline in influenza-related mortality among people aged 65 to 74 years in the decade after the 1968 pandemic to the acquisition of immunity to the emerging A(H3N2) virus. We could not correlate increasing vaccination coverage after 1980 with declining mortality rates in any age group. Because fewer than 10% of all winter deaths were attributable to influenza in any season, we conclude that observational studies substantially overestimate vaccination benefit.

And in a response to a critique of this paper, the authors write (in Arch Intern Med. Vol. 165 No. 17, September 26, 2005):

We disagree with Thompson and colleagues' assertion that our trends study is less robust compared with cohort studies. The strength of our approach is that, unlike cohort studies, we analyzed all deaths in the total elderly US population and are free of the biases to which cohort studies are subject. The comments by Thompson et al are surprising given that they used a similar study design and also found an increase in influenza-related mortality in recent years, which they suggested could be partially explained by aging of the population. Nevertheless, the critique by Thompson et al centers on our modeling assumptions, most of which were addressed in our article, including the duration of epidemic periods. We have provided age-adjusted excess mortality estimates, which addressed the paradoxical observation that mortality rates increased concomitant with a quadrupling in elderly vaccination coverage.