ETIOLOGY OF LEPROSY

M. leprae is an obligate intracellular bacillus (0.3 to 1 µm wide and 1 to 8 µm long) that is acid-fast, indistinguishable microscopically from other mycobacteria, and ideally detected in tissue sections by a modified Fite stain. Strain variability was recently discovered 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+ to 6+ in untreated patients, falling by one unit per year during effective therapy; the rate of fall is independent of the relative potency of effective antimicrobial therapy. A rising MI or BI suggests relapse and perhaps—if the patient is being treated—drug resistance; the latter possibility can be confirmed or excluded in the mouse model.

As a result of reductive evolution, almost half of the M. leprae genome contains nonfunctional genes; only 1605 genes encode for proteins. 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 recent finding of strain variability among M. leprae isolates provides a powerful tool with which to address anew the organism’s epidemiology and pathobiology. The bacterium’s complex cell wall has a peptidoglycan backbone, which is linked to arabinogalactan and mycolic acids. Lipoarabinomannan is a key component of the cell membrane, and the outer capsule contains large amounts of an M. leprae–specific phenolic glycolipid (PGL-1), which is detected in serologic tests.

Among the mycobacteria, M. leprae is unique in exhibiting dopa oxidase activity and an acid-fastness that is pyridine-extractable. 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).

Source: Harrison_s_Principles_of_Internal_Medicine_16th_Edition