Gradual changes in the age distribution of excess deaths in the years following the 1918 influenza pandemic in Copenhagen: using epidemiological evidence to detect antigenic drift

Background: The 1918 influenza pandemic was associated with an unusual age pattern of mortality, with most deaths occurring among young adults. Few studies have addressed changes in the age distribution for influenza-related mortality in the pre-pandemic and post-pandemic period, which has implications for pandemic preparedness. In the present paper, we analyse the age patterns of influenza-related excess mortality in the decades before and after the 1918 pandemic, using detailed historic surveillance data from Copenhagen.

Methods: Weekly age-specific rates of respiratory mortality and influenza-like-illnesses were compiled for 1904-1937. Seasonal excess rates of morbidity and mortality attributable to influenza were calculated using a seasonal regression approach. To characterize the age patterns of influenza-related deaths in individual seasons, we used two rate ratio (RR) measures representing ratios of excess mortality rates between age groups and influenza seasons.

Results: Individuals aged 15-64 years experienced sharply elevated excess respiratory mortality rates in the 1918-1919 and 1919-1920 pandemic periods, compared to pre-pandemic seasons (RR for excess mortality in the fall of 1918 = 67 relative to inter-pandemic seasons). Of all excess respiratory deaths occurring during 1918-1919, 84% were reported in individuals 15-64 years. By contrast, seniors over 65 years of age experienced no measurable excess mortality during 1918-1919 and moderate excess mortality in the recrudescent pandemic wave of 1919-1920. The first post-pandemic season associated with high excess mortality rates in individuals over 65 years was 1928-1929, with 73% of excess deaths occurring among seniors. We estimate that the age patterns of influenza-related mortality returned to pre-pandemic levels after 1925, based on trends in the rate ratio of excess respiratory mortality in people under and over 65 years.

Conclusions: The unusual elevation of excess respiratory mortality rates in young and middle-aged adults was confined to the first three years of A/H1N1 virus circulation 1918-1920; the rapid return to "epidemic" mortality pattern in this age group was probably due to high attack rates and build-up of immunity. In contrast, seniors were completely spared from pandemic mortality during 1918-1919, likely due to childhood exposure to an A/H1-like influenza virus. The rise in excess mortality rates in seniors in the recrudescent pandemic wave of 1919-1920 may suggest the emergence of an early influenza A/H1N1 drift variant. Subsequent drift events may have been associated with the particularly severe 1928-1929 epidemic in Denmark and elsewhere.