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

Alain Gagnon,Joaquín Madrenas,David JD. Earn,D. Ann Herring,Robert Bourbeau,Stacey A. Hallman,Matthew S. Miller,Paul Digard

doi:10.1371/journal.pone.0069586

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.

Highlights

The atypically high mortality among young adults during the 1918 influenza pandemic remains unexplained and continues to trouble virologists and immunologists [1]
Following the ‘‘original antigenic sin’’ [4,5] or the ‘‘antigenic imprinting’’ [6] hypotheses, and adding insights from Shanks and Brundage [7] on T-cell dysregulation, we propose that development of immunological memory to a specific influenza strain early in life may dysregulate the immune response and increase the risk of death when encountering a novel and highly antigenically dissimilar strain in later life
Emergence of virulent influenza viruses through antigenic shift and drift remains a significant threat to public health [18]

Summary

Introduction

The atypically high mortality among young adults during the 1918 influenza pandemic remains unexplained and continues to trouble virologists and immunologists [1]. Exploring the shape of the distribution of deaths leads us to propose immunological mechanisms that may help explain the atypically high young adult mortality in 1918, and relate that unusual pattern to prior exposure to the Russian influenza pandemic in 1889–90.

Results

Conclusion