The Role of Tuberculosis in Characterizing the Age-specific Risk of Severe Influenza from 1918-19
Welling Oei, ..
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The W-shaped age-specific mortality curve from the latest influenza pandemic in 2009, caused by the new influenza A (H1N1), has only been previously seen in one other flu epidemic, the highly fatal influenza pandemic of 1918, referred to as Spanish flu. An understanding of this atypical W-shaped feature of the Spanish flu, compared to the usual U-shape seen in other pandemics, is required to improve decision making. The aim of our study is to develop a formal hypothesis that tuberculosis (TB) was responsible for the W-shaped mortality in the Spanish flu pandemic. We obtained data from published epidemic records of Spanish flu in the United States of America, Japan, Iceland and the Netherlands, an epidemiological investigation of Spanish flu in TB and non-TB individuals in a Swiss sanatorium and TB mortality data across age, time and space in the three countries during the period 1900-1940. Three distinct steps of analyses were performed: Descriptive analyses of influenza mortality, morbidity, and case fatality ratio; Causal inference 2x2 table of TB infection vs influenza deaths; And analyses of epidemiological trends of TB mortality that separate the effect of age, period, and cohort. The study shows that the W-shaped pattern was seen not only in the mortality, but also in the case fatality, suggesting an underlying risk factor elevating the risk of influenza death. Causal inference between TB and influenza mortality given influenza infection showed that among those non-TB individuals, none died of influenza. The Age-Period-Cohort (APC) model was the best model to explain trends of TB mortality. The model showed that TB was 'washed out' during 1918, i.e. deaths resulting from the Spanish flu was in fact subtracted from future TB mortality, which was illustrated by a spike and followed by a constant decline thereafter. We concluded our study demonstrated, through various theoretical exercises, that TB may have been responsible for the W-shaped mortality curve of the Spanish flu.