The Relationship between Tuberculosis and Influenza Death during the Influenza (H1N1) Pandemic from 1918-19

The epidemiological mechanisms behind the W-shaped age-specific influenza mortality during the Spanish influenza (H1N1) pandemic 1918-19 have yet to be fully clarified. The present study aimed to develop a formal hypothesis: tuberculosis (TB) was associated with the W-shaped influenza mortality from 1918-19. Three pieces of epidemiological information were assessed: (i) the epidemic records containing the age-specific numbers of cases and deaths of influenza from 1918-19, (ii) an outbreak record of influenza in a Swiss TB sanatorium during the pandemic, and (iii) the age-dependent TB mortality over time in the early 20th century. Analyzing the data (i), we found that the W-shaped pattern was not only seen in mortality but also in the age-specific case fatality ratio, suggesting the presence of underlying age-specific risk factor(s) of influenza death among young adults. From the data (ii), TB was shown to be associated with influenza death (P = 0.09), and there was no influenza death among non-TB controls. The data (iii) were analyzed by employing the age-period-cohort model, revealing harvesting effect in the period function of TB mortality shortly after the 1918-19 pandemic. These findings suggest that it is worthwhile to further explore the role of TB in characterizing the age-specific risk of influenza death.