Tuberculosis and leprosy in perspective.

Two of humankind's most socially and psychologically devastating diseases, tuberculosis and leprosy, have been the subject of intensive paleopathological research due to their antiquity, a presumed association with human settlement and subsistence patterns, and their propensity to leave characteristic lesions on skeletal and mummified remains. Despite a long history of medical research and the development of effective chemotherapy, these diseases remain global health threats even in the 21st century, and as such, their causative agents Mycobacterium tuberculosis and M. leprae, respectively, have recently been the subject of molecular genetics research. The new genome-level data for several mycobacterial species have informed extensive phylogenetic analyses that call into question previously accepted theories concerning the origins and antiquity of these diseases. Of special note is the fact that all new models are in broad agreement that human TB predated that in other animals, including cattle and other domesticates, and that this disease originated at least 35,000 years ago and probably closer to 2.6 million years ago. In this work, we review current phylogenetic and biogeographic models derived from molecular biology and explore their implications for the global development of TB and leprosy, past and present. In so doing, we also briefly review the skeletal evidence for TB and leprosy, explore the current status of these pathogens, critically consider current methods for identifying ancient mycobacterial DNA, and evaluate coevolutionary models. Copyright 2009 Wiley-Liss, Inc.