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American Journal of Epidemiology Advance Access originally published online on January 27, 2008
American Journal of Epidemiology 2008 167(7):814-819; doi:10.1093/aje/kwm376
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American Journal of Epidemiology © The Author 2008. Published by the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org.

ORIGINAL CONTRIBUTIONS

Genetic Susceptibility to Severe Infection in Families with Invasive Pneumococcal Disease

Thomas Hjuler1, Gry Poulsen1, Jan Wohlfahrt1, Margit Kaltoft2, Robert J. Biggar1,3 and Mads Melbye1

1 Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark
2 Department of Bacteriology, Mycology and Parasitology, Statens Serum Institut, Copenhagen, Denmark
3 Viral Epidemiology Branch, National Cancer Institute, Bethesda, MD

Correspondence to Dr. Thomas Hjuler, Department of Epidemiology Research, Statens Serum Institut, Artillerivej 5, DK-2300 Copenhagen S, Denmark (e-mail: tta{at}ssi.dk).

Received for publication June 30, 2007. Accepted for publication December 3, 2007.

Severe infections may be influenced by genetic constitution. The authors examined familial aggregation of invasive infections, using invasive pneumococcal disease (IPD) as the index condition to ascertain families at risk. From Danish national registers, they identified relatives of persons with IPD from 1977 through 2005. Risks of IPD, bacterial meningitis, septicemia, and any invasive infection were analyzed for relatives of IPD cases in a prospective cohort study (23 million person-years). In total, 43,134 persons were found to have an IPD case in the family. The authors observed an increased risk of invasive infections in relatives of IPD cases most likely sharing the same household (parents, offspring, siblings, half-siblings), but only regarding those events within 1 year of the index IPD diagnosis (rate ratio = 7.4, 95% confidence interval: 2.4, 23.0). After 1 year, there were no increased risks of severe infections, including IPD, in close relatives. For other relatives, no increased risks of severe infections were observed at any time. No aggregation of invasive infections in IPD relatives was found, other than for close events among relatives who most likely shared the same household. Thus, at the population level, genetic constitution appears of little importance in the development of IPD and other severe infections.

cohort studies; genetic predisposition to disease; pneumococcal infections; population

Abbreviations: ICD-8, International Classification of Diseases, Eighth Revision; ICD-10, International Statistical Classification of Diseases and Related Health Problems, Tenth Revision; IPD, invasive pneumococcal disease


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