Spatial-temporal excess mortality patterns of the 1918-1919 influenza pandemic in Spain

Abstract

Background: The impact of socio-demographic factors and baseline health on the mortality burden of seasonal and pandemic influenza remains debated. Here we analyzed the spatial-temporal mortality patterns of the 1918 influenza pandemic in Spain, one of the countries of Europe that experienced the highest mortality burden.

Methods: We analyzed monthly death rates from respiratory diseases and all-causes across 49 provinces of Spain, including the Canary and Balearic Islands, during the period January-1915 to June-1919. We estimated the influenza-related excess death rates and risk of death relative to baseline mortality by pandemic wave and province. We then explored the association between pandemic excess mortality rates and health and socio-demographic factors, which included population size and age structure, population density, infant mortality rates, baseline death rates, and urbanization.

Results: Our analysis revealed high geographic heterogeneity in pandemic mortality impact. We identified 3 pandemic waves of varying timing and intensity covering the period from Jan-1918 to Jun-1919, with the highest pandemic-related excess mortality rates occurring during the months of October-November 1918 across all Spanish provinces. Cumulative excess mortality rates followed a south-north gradient after controlling for demographic factors, with the North experiencing highest excess mortality rates. A model that included latitude, population density, and the proportion of children living in provinces explained about 40% of the geographic variability in cumulative excess death rates during 1918-19, but different factors explained mortality variation in each wave.

Conclusions: A substantial fraction of the variability in excess mortality rates across Spanish provinces remained unexplained, which suggests that other unidentified factors such as comorbidities, climate and background immunity may have affected the 1918-19 pandemic mortality rates. Further archeo-epidemiological research should concentrate on identifying settings with combined availability of local historical mortality records and information on the prevalence of underlying risk factors, or patient-level clinical data, to further clarify the drivers of 1918 pandemic influenza mortality.

Figure 1

Monthly respiratory deaths per 10,000 people in three representative provinces of Spain, Jan-1915 to June-1919. The black curve is the monthly number of respiratory deaths. Shaded areas highlight time periods of high mortality associated with the 1918–1919 pandemic in Spain. The Serfling seasonal regression model baseline (blue curve) and corresponding upper limit of the 95% confidence interval of the baseline (red curve) are also shown. Excess deaths are above the upper limit of the baseline mortality curve calibrated using mortality levels prior to the 1918 influenza pandemic.

Figure 2

Monthly respiratory deaths per 10,000 people in 49 provinces of Spain, Jan-1915 to June-1919. The black curve is the monthly number of respiratory deaths. Vertical green dashed lines indicate the presence of summer mortality waves whenever respiratory mortality rates exceeded the seasonal mortality baseline in any spring-summer month. The Serfling seasonal regression model baseline (blue curve) and corresponding upper limit of the 95% confidence interval of the baseline (red curve) are also shown. Excess deaths are above the upper limit of the baseline mortality curve calibrated using mortality levels prior to the 1918 influenza pandemic. Individual figures display different scales in the Y-axis.

Figure 3

Excess respiratory mortality rates per 10,000 across 49 provinces of Spain. Results are shown for three pandemic periods (May-July 1918, August 1918-December 1918, and January 1919-April 1919) and sorted from high to low excess death rates. Excess deaths are above the upper limit of the baseline mortality curve calibrated using respiratory monthly mortality levels prior to the 1918 influenza pandemic.

Figure 4

Maps of excess respiratory deaths rates per 10,000 across provinces of Spain. Maps are shown for three pandemic periods corresponding to spring (May 1918-July 1918), fall (August 1918-December 1918), and winter (January 1919-April 1919) pandemic waves and the cumulative excess respiratory death rate associated with the 1918–1919 influenza pandemic.