Searching for Sharp Drops in the Incidence of Pandemic A/H1N1 Influenza by Single Year of Age

Abstract

BackgroundDuring the 2009 H1N1 pandemic (pH1N1), morbidity and mortality sparing was observed among the elderly population; it was hypothesized that this age group benefited from immunity to pH1N1 due to cross-reactive antibodies generated from prior infection with antigenically similar influenza viruses. Evidence from serologic studies and genetic similarities between pH1N1 and historical influenza viruses suggest that the incidence of pH1N1 cases should drop markedly in age cohorts born prior to the disappearance of H1N1 in 1957, namely those at least 52–53 years old in 2009, but the precise range of ages affected has not been delineated.Methods and FindingsTo test for any age-associated discontinuities in pH1N1 incidence, we aggregated laboratory-confirmed pH1N1 case data from 8 jurisdictions in 7 countries, stratified by single year of age, sex (when available), and hospitalization status. Using single year of age population denominators, we generated smoothed curves of the weighted risk ratio of pH1N1 incidence, and looked for sharp drops at varying age bandwidths, defined as a significantly negative second derivative. Analyses stratified by hospitalization status and sex were used to test alternative explanations for observed discontinuities. We found that the risk of laboratory-confirmed infection with pH1N1 declines with age, but that there was a statistically significant leveling off or increase in risk from about 45 to 50 years of age, after which a sharp drop in risk occurs until the late fifties. This trend was more pronounced in hospitalized cases and in women and was independent of the choice in smoothing parameters. The age range at which the decline in risk accelerates corresponds to the cohort born between 1951–1959 (hospitalized) and 1953–1960 (not hospitalized).ConclusionsThe reduced incidence of pH1N1 disease in older individuals shows a detailed age-specific pattern consistent with protection conferred by exposure to influenza A/H1N1 viruses circulating before 1957.

Immune history and influenza virus susceptibility

“…Francis and others proposed that in 1918, primary exposures to previously circulating H1 subtypes lowered susceptibility in children and older adults [1,38]: although young adults had probably already been infected with other H1 viruses, their first exposure (presumably to an H3 virus that emerged in 1889–1890) may have precluded the development of a robust response to H1. Other evidence suggesting that the subtype of first exposure affects immunity to other subtypes in an original antigenic sin-like way comes from age-specific mortality patterns in 2009 [39] and the age distribution of H5N1 and H7N9 cases [40]. Neutralizing cross-reactive heterosubtypic antibodies appear uncommon [21], and thus a reduction in heterosubtypic antigen availability mediated by other cross-reactive immune responses, such as memory T cells, might explain this sin-like phenomenon.…”

Pandemic Influenza A/H1N1pdm in Italy: Age, Risk and Population Susceptibility

“…Several serological studies, conducted in different countries worldwide, have estimated overall attack rates and age-specific attack rates [4], comparing pre- and post-pandemic samples [5]. In Europe serial seroprevalence studies were carried out [6],[7], [8]–[19].…”

“…Among possible factors we hypothesized: i ) age-specific characteristics of the contact network might have determined differential age-specific risk of infection, e.g. much lower in elderly with respect to children and young adults [4], [26]; ii ) pre-pandemic immunity might have conferred a certain level of herd immunity in the population, thus limiting virus transmission, especially in elderly [6], [29].…”

Potential antigenic explanation for atypical H1N1 infections among middle-aged adults during the 2013–2014 influenza season

“…In 2009, an antigenically distinct H1N1 strain began infecting humans and caused a pandemic (1)(2)(3). Elderly individuals were less susceptible to 2009 pandemic H1N1 (pH1N1) viruses because of cross-reactive antibodies (Abs) elicited by infections with older sH1N1 strains (3)(4)(5)(6)(7). pH1N1 viruses have continued to circulate on a seasonal basis since 2009.…”