Title: Dynamics of tuberculosis infection in various populations during the 19th and 20th century: The impact of conservative and pharmaceutical treatments on epidemiological observations

Authors: Kara L. Holloway-Kew¹, Maciej Henneberg^2,3,4

Affiliations: ¹Deakin University, IMPACT – the Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Geelong, Australia; ²Biological and Comparative Anatomy Research Unit, School of Biomedicine, University of Adelaide, Adelaide, Australia; ³Institute of Evolutionary Medicine, University of Zurich, Zurich, Switzerland; ⁴Department of Archaeology, Flinders University, Adelaide, Australia

Abstract:

Background

Humans and the bacteria causing tuberculosis (Mycobacterium tuberculosis) have evolved together for thousands of years. This co-evolution of host and pathogen has now reached a state on the verge of commensalism, where many individuals are infected with the bacterium, but very few show signs and symptoms of tuberculosis. Pharmacotherapy to treat those who develop disease is useful, but has limitations. The development of drug resistance as well as patient non-compliance are significantly impacting the efficacy of pharmacological treatments. This leads to the question: what other options are available for treating tuberculosis? In the past, prior to the introduction of antibiotic therapies, the improvement of living conditions, sanitation and public health reforms were used in an attempt to reduce mortality from tuberculosis. This work examined the extent that these strategies were able to reduce mortality in 19th and 20th century populations and compare with the impact of the introduction of antibiotic treatments.

Methods

This work included previously published data gathered from historical records describing mortality from tuberculosis in several populations during the 19th and 20th centuries (Switzerland, England and Wales, USA, Norway, Japan and Brazil). Curvilinear regression fitting was used to examine the reduction in mortality before and after the introduction of the first antibiotic treatment for tuberculosis (streptomycin; 1946).

Results

Regression analyses showed a decline in tuberculosis mortality was already occurring in Switzerland, England and Wales, the USA and Norway prior to the introduction of antibiotic treatment. This occurred following a large number of public health interventions such as improved sanitation, public health acts, compulsory reporting of tuberculosis cases, sanatoria treatments and diagnostic techniques. Following the introduction of antibiotics, the mortality rate declined further, however, this had a smaller effect than the other strategies used previously. In Japan and Brazil, the reduction in mortality rate was largely driven by antibiotic treatments. Following the introduction of streptomycin, mortality rates declined rapidly in these countries, with a smaller contribution from public health strategies. The reduction in tuberculosis mortality observed in Switzerland, England and Wales, the USA and Norway was similar to that observed for Japan and Brazil. This suggests that public health measures may be just as effective as antibiotics for the treatment of tuberculosis disease.

Discussion

Mycobacterium tuberculosis has co-evolved with humans over time, changing into a relationship where the bacterium is more of a commensal organism than a pathogen. For the development of active disease, immune status is important, where individuals infected with the bacterium are not likely to develop signs and symptoms unless their immune function is reduced. Effective strategies against tuberculosis can therefore include enhancing immune function of the population such as by improving living conditions, nutrition and public health. This has been effective in the past; many individuals with active tuberculosis were able to recover from the disease after receiving treatment at a sanatorium. Improving immunity may be an important strategy against drug resistant tuberculosis, to help reduce mortality where the disease is re-emerging.