Influenza vaccination and mortality benefits: new insights, new opportunities.

Influenza vaccination control strategies in most countries rely on vaccination of seniors and other high risk groups. Although placebo-controlled randomized trials show influenza vaccine is effective in younger age groups, few seniors >70 years were studied even though they suffer >90% of influenza-related deaths. Excess mortality studies could not confirm a national decline in influenza-related mortality while vaccine coverage quadrupled. Cohort studies have consistently reported that vaccination reduces all-cause winter mortality by approximately 50%, an astonishing claim given only approximately 5% of all winter deaths are attributable to influenza. This VE overestimation has now been attributed to profound confounding frailty selection bias. A way forward includes a new generation of unbiased studies with laboratory endpoints, and requires an agreement that the evidence base was flawed. The latter may clear the way for more immunogenic vaccines for seniors and exploration of other influenza control strategies.