Lessons from the past: familial aggregation analysis of fatal pandemic influenza (Spanish flu) in Iceland in 1918

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.

Fig. 1.

Morbidity and fatality from the Spanish flu. (A) Morbidity in Reykjavik, Iceland, from October 28 to December 6, 1918. The number of new patient visits due to the illness is shown (n = 1,232), based on data from ref. . (B) Number of fatalities in Iceland from October 26 to December 6, 1918 (n = 448 with known date of death).

Fig. 2.

Age of fatal cases. (A) Age distribution of patients with fatal influenza in Iceland 1918. (B) Age-specific fatality proportion (%) of patients with fatal Spanish flu in Iceland, 1918 (n = 452). Three individuals had an unknown date of birth and are thus not included.

Fig. 3.

Geographical distribution by parish of fatalities (n = 437) due to Spanish influenza in Iceland in 1918. Parishes are color-coded to indicate the absolute number or range of fatalities. The black columns show the number of fatalities as a percentage of the total parish population (fatality proportion). For sake of clarity, columns were omitted in cases where there was only one fatality.