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

Abstract

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 to 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 1918-19 and 1919-20 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 1918-19, 84% were reported in individuals 15-64 yrs. By contrast, seniors over 65 years of age experienced no measurable excess mortality during 1918-19 and moderate excess mortality in the recrudescent pandemic wave of 1919-20. The first post-pandemic season associated with high excess mortality rates in individuals over 65 yrs was 1928-29, 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 1918-20; 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 1918-19, 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 1919-20 may suggest the emergence of an early influenza A/H1N1 drift variant. Subsequent drift events may have been associated with the particularly severe 1928-29 epidemic in Denmark and elsewhere.

WITHDRAWN: Intense Seasonal A/H1N1 Influenza in Mexico, Winter 2013–2014

“…The observed gradual change in age distribution of hospitalization and deaths in the post 2009 pandemic period is reminiscent of the influenza seasons following the 1918 influenza pandemic (6,21,22) and the 1968 pandemic (23). A quantitative analysis of excess mortality prior to and after the 1918 influenza pandemic found that the age distribution of influenza-related mortality returned to pre-pandemic mortality levels a few years after the initial pandemic waves as a result of emerging drift variants (6,24).…”

“…Because past influenza pandemics have had substantial morbidity and mortality burden for several seasons after the initial pandemic waves (6–10), continued vigilance is prudent in the post-pandemic period. The 2013–2014 influenza season was dominated by A/H1N1 in North America and prompted alarm due to its unusual severity in young and middle-aged adults (11,12).…”

Insights from unusual aspects of the 1918 influenza pandemic

“…Although there is good epidemiological evidence from Europe and genomic information from the USA to indicate that the lethal form of the virus was circulating months prior to its recognition in late 1918, there is no good explanation for how such a virus could suddenly and nearly simultaneously increase its lethality in multiple places across the globe [47,48]. Perhaps the "purulent bronchitis" epidemics observed in First World War soldiers from 1914 to 17 were actually the beginnings of the 1918 pandemic virus indicating that the virus had years to spread globally through the massive movement of people associated with the war [41,49e52].…”

“…The distinctive W mortality pattern of the 1918 virus disappeared early in the 1920s although influenza viruses with less mortality continued to circulate [47]. Recent genomic analyses based on all H1N1 viruses available indicate that what became seasonal influenza in the 1920s was quite different from the pandemic virus of 1918 [43].…”

COBRA-Based Dengue Tetravalent Vaccine Elicits Neutralizing Antibodies Against All Four Dengue Serotypes

“…However, a highly attractive potential vaccine candidate would be a non-infectious virus-like particle, which has been successfully used as a vaccine delivery platform for many viruses, as reviewed in [16].The sub viral particles (SVP) entities present structures physically similar to virions, but lack infectious RNA genome.…”