Age-specific mortality during the 1918 influenza pandemic: unravelling the mystery of high young adult mortality

PLoS One. 2013 Aug 5;8(8):e69586. doi: 10.1371/journal.pone.0069586. Print 2013.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age Distribution
  • Aged
  • Aged, 80 and over
  • Canada / epidemiology
  • Child
  • Child, Preschool
  • Female
  • Humans
  • Infant
  • Infant, Newborn
  • Influenza, Human / epidemiology
  • Influenza, Human / mortality*
  • Male
  • Middle Aged
  • Pandemics / statistics & numerical data
  • United States / epidemiology
  • Young Adult

Grant support

This work was supported by the Social Science and Humanity and Research council of Canada (AG, SAH, DAH, and RB), the Canadian Institutes of Health Research (AG, MSM, DJDE, and JM) and the Natural Sciences and Engineering Research Council of Canada (DJDE). JM holds a Tier I Canada Research Chair in Human Immunology. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.