Age-Specific Mortality During the 1918 Influenza Pandemic: Unravelling the Mystery of High Young Adult Mortality

Abstract

The worldwide spread of a novel influenza A (H1N1) virus in 2009 showed that influenza remains a significant health threat, even for individuals in the prime of life. This paper focuses on the unusually high young adult mortality observed during the Spanish flu pandemic of 1918. Using historical records from Canada and the U.S., we report a peak of mortality at the exact age of 28 during the pandemic and argue that this increased mortality resulted from an early life exposure to influenza during the previous Russian flu pandemic of 1889–90. We posit that in specific instances, development of immunological memory to an influenza virus strain in early life may lead to a dysregulated immune response to antigenically novel strains encountered in later life, thereby increasing the risk of death. Exposure during critical periods of development could also create holes in the T cell repertoire and impair fetal maturation in general, thereby increasing mortality from infectious diseases later in life. Knowledge of the age-pattern of susceptibility to mortality from influenza could improve crisis management during future influenza pandemics.

Genesis and pathogenesis of the 1918 pandemic H1N1 influenza A virus

“…1), the only age group in 1918 whose childhood exposure would have been almost exclusively to a fully heterosubtypic virus (H3N8) (also ref. 33). Note that the peak in excess mortality in 1918 (Fig.…”

“…First, a mechanism akin to original antigenic sin (OAS) (36) may have interfered with immune responses in some of those infected in 1918 (33,37), peaking in those exposed to the 1889 virus. Although OAS has been traditionally considered a within-subtype phenomenon (36,(38)(39)(40), it is plausible that interactions between heterosubtypic viruses could also occur (41).…”

“…These other pandemics have occurred against a backdrop of widespread prior exposure of the human population to a homosubtypic NA (1968,2009) and/or HA (1977,2009), or to a heterosubtypic but phylogenetically closely related HA (SI Appendix, Fig. S13) with a very similar HA stalk (1957) (33).…”

Insights from unusual aspects of the 1918 influenza pandemic

“…There have been several hypothesis put forward. The most important aspect seems to be the 1918 pandemic's relationship to the 1890 pandemic as there is no other way to explain a mortality peak at 28 y [5,9,10]. Exposure in infancy to infectious agents has different immunological implications to infections occurring later in life.…”

Low-dose cadmium potentiates lung inflammatory response to 2009 pandemic H1N1 influenza virus in mice

“…http://dx.doi.org/10.1101/346866 doi: bioRxiv preprint first posted online Jun. 14, 2018; demographic factors, such as age and general health (25,26). In most cases, the pandemic 2009 influenza A (H1N1) virus caused an uncomplicated respiratory tract illness with symptoms similar to those caused by seasonal influenza viruses.…”