Leprosy, first described in ancient Indian texts from the sixth century b.c., is a nonfatal, chronic infectious disease caused by Mycobacterium leprae, the clinical manifestations of which are largely confined to the skin, peripheral nervous system, upper respiratory tract, eyes, and testes. The unique tropism of M. leprae for peripheral nerves (from large nerve trunks to microscopic dermal nerves) and certain immunologically mediated reactional states are the major causes of morbidity in leprosy. The propensity of the disease, when untreated, to result in characteristic deformities and the recognition in most cultures that the disease is communicable from person to person have resulted historically in a profound social stigma. Today, with early diagnosis and the institution of appropriate and effective antimicrobial therapy, patients can lead productive lives in the community, and deformities and other visible manifestations can largely be prevented.
M. leprae is an obligate intracellular bacillus (0.3–1 μm wide and 1–8 μm long) that is confined to humans, armadillos in certain locales, and sphagnum moss. The organism is acid-fast, indistinguishable microscopically from other mycobacteria, and ideally detected in tissue sections by a modified Fite stain. Strain variability has been documented in this organism. M. leprae produces no known toxins and is well adapted to penetrate and reside within macrophages, yet it may survive outside the body for months. In untreated patients, only ∼1% of M. leprae organisms are viable. The morphologic index (MI), a measure of the number of acid-fast bacilli (AFB) in skin scrapings that stain uniformly bright, correlates with viability. The bacteriologic index (BI), a logarithmic-scaled measure of the density of M. leprae in the dermis, may be as high as 4–6+ in untreated patients and falls by 1 unit per year during effective antimicrobial therapy; the rate of decrease is independent of the relative potency of therapy. A rising MI or BI suggests relapse and perhaps—if the patient is being treated—drug resistance. Drug resistance can be confirmed or excluded in the mouse model of leprosy, and resistance to dapsone and rifampin can be documented by the recognition of mutant genes. However, the availability of these technologies is extremely limited.
As a result of reductive evolution, almost half of the M. leprae genome contains nonfunctional genes; only 1605 genes encode for proteins, and 1439 genes are shared with Mycobacterium tuberculosis. In contrast, M. tuberculosis uses 91% of its genome to encode for 4000 proteins. Among the lost genes in M. leprae are those for catabolic and respiratory pathways; transport systems; purine, methionine, and glutamine synthesis; and nitrogen regulation. The genome of M. leprae provides a metabolic rationale for its obligate intracellular existence and reliance on host biochemical support, a template for targets of drug development, and ultimately a pathway to cultivation. The finding of strain variability among M. leprae isolates has provided a powerful tool with which to address anew the organism's epidemiology and pathobiology and to determine whether relapse represents reactivation or reinfection. The bacterium's complex cell wall contains large amounts of an M. leprae–specific phenolic glycolipid (PGL-1), which is detected in serologic tests. The unique trisaccharide of M. leprae binds to the basal lamina of Schwann cells; this interaction is probably relevant to the fact that M. leprae is the only bacterium to invade peripheral nerves.
Although it was the first bacterium to be etiologically associated with human disease, M. leprae remains one of the few bacterial species that still has not been cultivated on artificial medium or tissue culture. The multiplication of M. leprae in mouse footpads (albeit limited, with a doubling time of ∼2 weeks) has provided a means to evaluate antimicrobial agents, monitor clinical trials, and screen vaccines. M. leprae grows best in cooler tissues (the skin, peripheral nerves, anterior chamber of the eye, upper respiratory tract, and testes), sparing warmer areas of the skin (the axilla, groin, scalp, and midline of the back).
Leprosy is almost exclusively a disease of the developing world, affecting areas of Asia, Africa, Latin America, and the Pacific (Fig. 166-1). While Africa has the highest disease prevalence, Asia has the most cases. More than 80% of the world's cases occur in a few countries: India, China, Myanmar, Indonesia, Brazil, Nigeria, Madagascar, and Nepal. Within endemic locales, the distribution of leprosy is quite uneven, with areas of high prevalence bordering on areas with little or no disease. In Brazil the majority of cases occur in the Amazon basin and two western states, while in Mexico leprosy is mostly confined to the Pacific coast. Except as imported cases, leprosy is largely absent from the United States, Canada, and northwestern Europe. In the United States, ∼4000 persons have leprosy and 100–200 new cases are reported annually, most of them in California, Texas, New York, and Hawaii among immigrants from Mexico, Southeast Asia, the Philippines, and the Caribbean. The comparative genomics of single-nucleotide polymorphisms support the likelihood that four distinct strains exist, having originated in East Africa or Central Asia. A mutation spread to Europe and subsequently underwent two separate mutations that were then followed by spread to West Africa and the Americas.
Estimated prevalence of leprosy at the turn of the millennium. Because data on leprosy prevalence in many endemic countries are unreliable, global prevalence is difficult to assess with any great degree of accuracy; however, it is not falling (see text). (Courtesy of Patrick J. Brennan, PhD, with permission.)
The global prevalence of leprosy is difficult to assess, given that many of the locales with high prevalence lack a significant medical or public health infrastructure. Estimates range from 0.6 to 8 million affected individuals. The lower estimate includes only persons who have not completed chemotherapy, excluding those who may be ...