title: 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.
authors.affiliation: Landspitali University Hospital, 108 Reykjavik, Iceland. magnusgo@landspitali.is
authors.forename: Magnús
authors.initials: M
authors.lastname: Gottfredsson
authors.forename: Bjarni V
authors.initials: BV
authors.lastname: Halldórsson
authors.forename: Stefán
authors.initials: S
authors.lastname: Jónsson
authors.forename: Már
authors.initials: M
authors.lastname: Kristjánsson
authors.forename: Kristleifur
authors.initials: K
authors.lastname: Kristjánsson
authors.forename: Karl G
authors.initials: KG
authors.lastname: Kristinsson
authors.forename: Arthur
authors.initials: A
authors.lastname: Löve
authors.forename: Thorsteinn
authors.initials: T
authors.lastname: Blöndal
authors.forename: Cécile
authors.initials: C
authors.lastname: Viboud
authors.forename: Sverrir
authors.initials: S
authors.lastname: Thorvaldsson
authors.forename: Agnar
authors.initials: A
authors.lastname: Helgason
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Gulcher
authors.forename: Kári
authors.initials: K
authors.lastname: Stefánsson
authors.forename: Ingileif
authors.initials: I
authors.lastname: Jónsdóttir
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D004196:Disease Outbreaks; D005190:Family; D005260:Female; D020022:Genetic Predisposition to Disease; D049673:History, 20th Century; D006801:Humans; D007055:Iceland / Q000453:epidemiology; D007223:Infant; D007231:Infant, Newborn; D007251:Influenza, Human / Q000453:epidemiology / Q000235:genetics* / Q000266:history / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis