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Previous Volume 361:2000-2001 November 12, 2009 Number 20 Next

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To the Editor: Early epidemiologic reports regarding the 2009 pandemic influenza A (H1N1) virus suggest that cases of infection and deaths are concentrated in adults between the ages of 20 and 40 years.¹ This finding could reflect age-related differences in susceptibility or differential testing and diagnosis in this age group. Increased susceptibility to infection in young persons is characteristic of influenza pandemics and has important implications for disease-control policy.² We examined whether the reported excess of cases in younger persons derives from testing practices or reflects a differential risk of infection in Ontario, Canada.

Our study sample included all persons who were tested for 2009 H1N1 virus infection under an enhanced, provincewide, laboratory-based surveillance regimen from April 20, 2009, to June 10, 2009. Patients with confirmed infection were compared with those who tested negative for the 2009 H1N1 virus. Using multivariate logistic regression and zero-inflated Poisson regression, we evaluated the association between age group (which was defined according to the relationship between birth year and the predominant circulating influenza strains) and the risk of infection with the 2009 H1N1 virus.

Of 11,560 patients who were tested, 1819 (15.7%) had positive results for the 2009 H1N1 virus. Persons who were born before 1957 had a reduced risk of infection, and estimates did not substantially change after adjustment for travel to Mexico, public health unit of residence, or calendar week (adjusted odds ratio for older age group, 0.15; 95% confidence interval [CI], 0.12 to 0.18; unadjusted odds ratio; 0.17; 95% CI, 0.14 to 0.21). Persons who were born between 1957 and 1975 were at intermediate risk for infection (adjusted odds ratio, 0.42; 95% CI, 0.37 to 0.48). Similar effects were seen in zero-inflated Poisson models that used testing volumes and population as model offsets. There was no significant relationship between age group and the risk of infection with seasonal influenza A viruses (either H3N2 or H1N1) (Figure 1).

View larger version (20K): [in this window] [in a new window]   Figure 1. Age-Related Probability of Seasonal Influenza A and 2009 H1N1 Influenza in 11,560 Tested Patients. Patients who were born after 1957 (i.e., 53 years of age) have an increased risk of infection with the 2009 pandemic influenza A (H1N1) virus. The results of testing show no significant relationship between age group and the risk of infection with seasonal influenza A viruses (either H3N2 or H1N1).

 
Among persons who were at risk for infection with 2009 H1N1 virus, being born before 1957 was associated with a lower infection risk. The reduced number of infections was not simply a reflection of decreased testing in this group. The mechanism for this association is unclear but is compatible with the reported age-related increase in the prevalence of neutralizing antibody titers against the 2009 H1N1 virus³ and may reflect some immunity to infection as a result of exposure to similar viruses in early life. Maximally effective host immune responses to influenza may be generated by early-life infections.⁴ These findings are consistent with the high frequency of outbreaks of 2009 H1N1 influenza in schools⁵ and the decreased frequency of outbreaks in long-term care facilities that have been associated with this pandemic virus to date.

David N. Fisman, M.D., M.P.H.
University of Toronto
Toronto, ON, Canada
david.fisman{at}gmail.com

Rachel Savage, M.Sc.
Jonathan Gubbay, M.B., B.S.
Camille Achonu, M.H.Sc.
Holy Akwar, D.V.M., Ph.D.
David J. Farrell, Ph.D.
Natasha S. Crowcroft, M.B., B.S., Ph.D.
Ontario Agency for Health Protection and Promotion
Toronto, ON, Canada

Phil Jackson, M.A.
468 Delaware Ave.
Toronto, ON, Canada

Dr. Fisman reports receiving research support from Sanofi Pasteur. No other potential conflict of interest relevant to this letter was reported.

References

1. Chowell G, Bertozzi SM, Colchero MA, et al. Severe respiratory disease concurrent with the circulation of H1N1 influenza. N Engl J Med 2009;361:674-679. [Free Full Text]
2. Miller MA, Viboud C, Olson DR, Grais RF, Rabaa MA, Simonsen L. Prioritization of influenza pandemic vaccination to minimize years of life lost. J Infect Dis 2008;198:305-311. [CrossRef][Web of Science][Medline]
3. Hancock K, Veguilla V, Lu X, et al. Cross-reactive antibody responses to the 2009 pandemic H1N1 influenza virus. N Engl J Med 2009;361:1945-1952. [Free Full Text]
4. Webster RG. Original antigenic sin in ferrets: the response to sequential infections with influenza viruses. J Immunol 1966;97:177-183. [Free Full Text]
5. Cutler J, Schleihauf E, Hatchette TF, et al. Investigation of the first cases of human-to-human infection with the new swine-origin influenza A (H1N1) virus in Canada. CMAJ 2009;181:159-63

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