Tuberculosis is an evolving disease: paleoepidemiological and historical evidence.

Abstract

Tuberculosis is a systemic infection responsible for approximately 20 to 25% of all deaths in Europe during the 18th century. The disease is spread by close contact with infected humans or animals (e.g. aerosol droplets generated through coughing, drinking infected milk). Even when persons become infected with tuberculosis, they may not show signs or symptoms. In fact, only approximately 10% of infected individuals will develop active disease. This is related to the levels of immunity of the patient; only when immunity has been lowered sufficiently will signs and symptoms develop. Active disease rarely leads to skeletal lesions (3-5% of active cases) but can occur if the bacterium enters the bloodstream. These lesions usually affect vertebrae, but also the hip and knee. At present, tuberculosis is re-emerging after a long decline and is developing resistance to drugs. The World Health Organization estimates that approximately one third of the world’s population is infected. There have been reports of strains with resistance to multiple drugs (MDR-TB) as well as extensive drug resistance (XDR-TB). This thesis seeks to show that tuberculosis is not just a disease, but a balance and co-evolution between host and pathogen. Previous literature has shown that when immunity is high enough, tuberculosis can have very low mortality rates. Pharmacotherapies (antibiotics plus isoniazid and PAS) are not necessary for this and conservative measures can be used instead. In order to accomplish this, this research involved several parts; each focussing on a separate time scale. The first analysis was over a long time period (7250 BCE to 1899) and involved the meta-analysis of all reported paleopathological cases of tuberculosis in the literature (N=531). Results showed frequency of skeletal lesions significantly decreased over time (P<0.05) and the distribution of skeletal lesions changed during this same period (P<0.01). The second analysis involved a much shorter time period (1840-1935) of the second epidemiological transition in Switzerland. This research examined the effect of specific factors in the decline of tuberculosis during the 19th and 20th centuries. This showed the impact of improved living conditions and general health on tuberculosis mortality. The third analysis further investigates the effects of good immunity on skeletal lesions. The Galler Collection contained skeletal remains and medical records of individuals with tuberculosis. This investigation showed how healthcare can result in “healing” of tuberculous skeletal lesions. This research also serves as a guide for paleopathological analyses. Finally, logistic modelling of tuberculosis mortality in six countries showed reasons for the decline in certain areas. This investigation allowed the understanding of effectiveness of strategies in controlling tuberculosis. Public health measures and sanitation were found to be useful, but antibiotic use resulted in the fastest rate of decline. Milk quality control was important where bovine tuberculosis was at high levels. The information gathered from these four investigations allows more efficient and cost effective treatment measures to be proposed for areas of the world where tuberculosis is re-emerging. These treatment strategies will also aid in the fight against strains of MDR and XDR tuberculosis.