Age-specific mortality risk from pandemic influenza

Younger age groups account for proportionally more mortality in influenza pandemics than in seasonal influenza epidemics. Mechanisms that might explain this include young people suffering from an over-reactive immune system (“cytokine storm”), older people benefiting from cross-immunity from a wider variety of previous influenza infections (“antigenic history”), and lifetime immune responses in all people being shaped by their first influenza A infection (“antigenic imprinting” or “original antigenic sin”). We examined whether these mechanisms can explain age-specific influenza mortality patterns, using the complete database of individual deaths in Canada from 1951 to 1999. The mortality pattern during the 1957 pandemic indicates that antigenic imprinting plays an important role in determining age-specific influenza virulence and that both shift years and major drift years contribute significantly to antigenic imprints. This information should help pandemic planners to identify age groups that might respond differently to novel influenza strains.

► We discuss the pattern of mortality with age from historical influenza pandemics.
► We compare and contrast several proposed explanations for this pattern.
► We evaluate these proposals using a database of Canadian deaths from 1951 to 1999.
► We find that “antigenic imprinting” is the simplest explanation of these patterns.
► These results should be useful for analyzing mortality patterns in future epidemics.