Lessons from the past: Familial aggregation analysis of fatal pandemic influenza (Spanish flu) in Iceland in 1918
- Magnús Gottfredsson*,†,‡,
- Bjarni V. Halldórsson§,
- Stefán Jónsson§,¶,
- Már Kristjánsson*,
- Kristleifur Kristjánsson§,
- Karl G. Kristinsson*,†,
- Arthur Löve*,†,
- Thorsteinn Blöndal*,
- Cécile Viboud‖,
- Sverrir Thorvaldsson§,
- Agnar Helgason†,§,
- Jeffrey R. Gulcher§,
- Kári Stefánsson†,§, and
- Ingileif Jónsdóttir*,†,§,‡
- *Landspitali University Hospital, 108 Reykjavik, Iceland;
- †Faculty of Medicine, University of Iceland, 101 Reykjavik, Iceland;
- §deCODE Genetics, 101 Reykjavik, Iceland; and
- ‖Fogarty International Center, National Institutes of Health, Bethesda, MD 20892
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Edited by Burton H. Singer, Princeton University, Princeton, NJ, and approved November 21, 2007 (received for review August 14, 2007)
Abstract
The pandemic influenza of 1918 (Spanish flu) killed 21–50 million people globally, including in Iceland, where the characteristics and spread of the epidemic were well documented. It has been postulated that genetic host factors may have contributed to this high mortality. We identified 455 individuals who died of the Spanish flu in Iceland during a 6-week period during the winter of 1918, representing >92% of all fatal domestic cases mentioned by historical accounts. The highest case fatality proportion was 2.8%, and peak excess mortality was 162/100,000/week. Fatality proportions were highest among infants, young adults, and the elderly. A genealogical database was used to study relatedness and relative risk (RR) of the fatal influenza victims and relatives of their unaffected mates. The significance of these RR computations was assessed by drawing samples randomly from the genealogical database matched for age, sex, and geographical distribution. Familial aggregation of fatalities was seen, with RRs for death ranging from 3.75 for first-degree relatives (P < 0.0001) to 1.82 (P = 0.005), 1.12 (P = 0.252), and 1.47 (P = 0.0001) for second- to fourth-degree relatives of fatal influenza victims, respectively. The RRs within the families of unaffected mates of fatal influenza victims were 2.95 (P < 0.0001), 1.27 (P = 0.267), 1.35 (P = 0.04), and 1.42 (P = 0.001), for first- to fourth-degree relatives, respectively. In conclusion, the risk of death from the Spanish flu was similar within families of patients who succumbed to the illness and within families of their mates who survived. Our data do not provide conclusive evidence for the role of genetic factors in susceptibility to the Spanish flu.
Footnotes
- ‡To whom correspondence may be addressed. E-mail: magnusgo{at}landspitali.is or ingileif.jonsdottir{at}decode.is
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Author contributions: M.G., B.V.H., K.S., and I.J. designed research; M.G. and B.V.H. performed research; M.G., B.V.H., C.V., A.H., K.S., and I.J. contributed new reagents/analytic tools; M.G., B.V.H., S.J., C.V., S.T., A.H., and I.J. analyzed data; and M.G., B.V.H., S.J., M.K., K.K., K.G.K., A.L., T.B., C.V., A.H., J.R.G., K.S., and I.J. wrote the paper.
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↵ ¶Deceased July 27, 2007.
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The authors declare no conflict of interest.
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This article is a PNAS Direct Submission.
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See Commentary on page 1109.
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Freely available online through the PNAS open access option.
- © 2008 by The National Academy of Sciences of the USA
