Leprosy or Hansen’s disease is a chronic infectious disease involving primarily the peripheral nervous system, skin, eyes, and mucous membranes. It is endemic in many countries in Asia, Africa, the Pacific Islands, Latin America, southern Europe, and the Middle East. There are endemic areas of infection in the United States as well, particularly in Gulf coast states and California. The major sequelae of leprosy are physical deformities involving the extremities, face, and eyes due primarily to damage to the sensory nerves from infection by organisms of the Mycobacterium leprae-complex (M. leprae and M. lepromatosis), and the immune reaction to those pathogens. The resultant deformities often lead to stigmatization that continues after the infection becomes inactive and the patient is not infectious.
Since several effective antileprosy drugs are now available, new cases of leprosy can be treated effectively and rendered noninfectious. Leprosy should not pose a significant public health problem once treatment is instituted. In fact, despite the recognized importation of 100–320 cases annually in the United States for the last few decades, the development of clinical leprosy among the contacts of these imported cases has not been documented.1
Leprosy is caused by M. leprae and its close relative, M. lepromatosis. These are weakly acid-fast bacteria that can be demonstrated in tissues using a modified acid-fast stain, the Fite-Faraco stain. M. leprae was originally identified in 1873 by Gerhard Henrik Armauer Hansen, and M. lepromatosis was recognized by DNA sequencing in 2008.2 These organisms have not yet been successfully cultivated in vitro.
M. leprae has one of the slowest replication cycles of any known bacteria: it divides only every 10–12 days during the log phase of growth, as determined from studies in mouse footpads. The organism replicates in mouse footpads,3 in thymectomized mice or rats, nude mice, severe combined immunodeficient mice, the nine-banded armadillo, and in several nonhuman primate species.4 Naturally occurring leprosy infections have been documented in nine-banded armadillos (Dasypus novemcinctus),5 chimpanzees, and sooty mangabeys.6 M. lepromatosis has recently been found in red squirrels in the United Kingdom.7–9 The complete genome sequences of M. leprae and M. lepromatosis have been reported, and they are very similar.10 The M. leprae genome contains 3.3 million base pairs compared to 4.4 million base pairs in the M. tuberculosis genome. However, in contrast with the M. tuberculosis genome, less than half of the M. leprae genome encodes functional genes, but pseudogenes with intact counterparts of M. tuberculosis are common. Gene deletion and decay eliminated many important metabolic activities, including part of the oxidative and most of the microaerophilic and anaerobic respiratory chains and numerous catabolic systems and regulatory circuits in M. leprae. The reductive evolution indicated by the M. leprae genome’s structure explains its slow growth and limited metabolic capability.11