Mycobacterium leprae, the causative agent of leprosy, is an unusual organism that presents unique challenges to those studying the disease through molecular epidemiology. As a consequence, many basic aspects of disease transmission and biology remain unilluminated. In this review, we explore the general principles of molecular epidemiology, and the special difficulties surrounding the application of molecular epidemiology to M. leprae. We briefly discuss the computational tools commonly employed in molecular epidemiology studies. The past decade of developments in molecular strain typing approaches through VNTRs and SNP loci, and their merits and limitations, are discussed. We summarize what has been learned about the transmission and historical origins of leprosy through molecular epidemiology and Bacterial Population Genetics, to date. Lastly, we critically evaluate the strengths and shortcomings of leprosy research, and present recommendations for future work that will hopefully shed light on some of the disease's most fundamental mysteries.
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