title: Searching for sharp drops in the incidence of pandemic A/H1N1 influenza by single year of age.
abstract: BACKGROUND
  During 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.
  
  
  RESULTS
  To 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).
  
  
  CONCLUSIONS
  The 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.
authors.affiliation: Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, United States of America. jhartman44@gmail.com
authors.forename: Jessica Hartman
authors.initials: JH
authors.lastname: Jacobs
authors.forename: Brett Nicholas
authors.initials: BN
authors.lastname: Archer
authors.forename: Michael G
authors.initials: MG
authors.lastname: Baker
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Cowling
authors.forename: Richard T
authors.initials: RT
authors.lastname: Heffernan
authors.forename: Geoff
authors.initials: G
authors.lastname: Mercer
authors.forename: Osvaldo
authors.initials: O
authors.lastname: Uez
authors.forename: Wanna
authors.initials: W
authors.lastname: Hanshaoworakul
authors.forename: Cécile
authors.initials: C
authors.lastname: Viboud
authors.forename: Joel
authors.initials: J
authors.lastname: Schwartz
authors.forename: Eric
authors.initials: E
authors.lastname: Tchetgen Tchetgen
authors.forename: Marc
authors.initials: M
authors.lastname: Lipsitch
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D005260:Female; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D015994:Incidence; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007251:Influenza, Human / Q000453:epidemiology*; D008297:Male; D008875:Middle Aged; D058873:Pandemics; D012737:Sex Factors; D055815:Young Adult