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

Abstract

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.

Age-Dependent Estimates of the Epidemiological Impact of Pandemic Influenza (H1N1-2009) in Japan

“…It has been well known that only a portion of ILI cases that are reported through the surveillance system are truly influenza, and those caused by other etiological agents (e.g., other viral infections) contribute to contaminating the number of cases [19, 20]. Thus, there is a possibility that some of the cases reported as ILI were actually attributed to other upper respiratory virus infections such as the respiratory syncytial virus (RSV).…”

Excess Mortality Associated with Influenza among Tuberculosis Deaths in South Africa, 1999–2009

“…Review of data from the 1918 influenza pandemic suggests that many individuals who died had active tuberculosis [14, 15] and that underlying tuberculosis infection may have contributed to the elevated mortality observed in young adults [15, 16]. However, limited data are available on excess mortality associated with seasonal influenza infection among patients with tuberculosis.…”

Influenza A Virus Impairs Control of Mycobacterium tuberculosis Coinfection Through a Type I Interferon Receptor–Dependent Pathway

“…Mathematical modeling, particularly of epidemiological data from influenza pandemics, point to an association between M. tuberculosis and IAV coinfection and increased mortality [7]. Only 1 study, published in 1947, has experimentally addressed the question of whether IAV increases susceptibility to tuberculosis in mice [8].…”