Pathogenesis

The earliest detectable finding in human infection with M. leprae is generally the invasion of the small nerves of the skin demonstrated by biopsy of skin lesions. Indeed, M. leprae is the only known human pathogen that preferentially attacks the peripheral nerves. The bacterium also initially grows very well within macrophages, before delayed hypersensitivity develops. The course of the infection depends on the immune response of the host. In most cases, cellular immunity and delayed hyper-sensitivity develop against the invading bacteria. Immune macrophages limit the growth of M. leprae, and the bacteria therefore do not become numerous. The attack of immune cells against chronically infected nerve cells can progressively damage the nerves, however, which leads to disabling deformity, resorption of bone, and skin ulceration. The disease often spontaneously stops progressing, and thereafter the nerve damage, although permanent, does not worsen. This limited type of Hansen's disease in which cellular immunity suppresses proliferation of the bacilli is called tuberculoid leprosy. People with tuberculoid leprosy rarely, if ever, transmit the disease to others. In many cases of tuberculoid leprosy, however, the immune system is gradually overwhelmed by the growth of M. leprae, leading to the more serious lepromatous form of the disease discussed in further detail next. Early treatment is important to prevent the disease from progressing. ■ macrophage, pp. 377,385 ■ delayed hypersensitivity, p. 449

When cellular immunity and delayed hypersensitivity to M. leprae fail to develop or are suppressed, unrestricted growth of M. leprae occurs in the cooler tissues of the body, notably in skin macrophages and peripheral nerves. This relatively uncommon

10 mm

Figure 26.10 Masses of Mycobacterium leprae in a Biopsy Specimen from a Person with Lepromatous Leprosy

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Figure 26.10 Masses of Mycobacterium leprae in a Biopsy Specimen from a Person with Lepromatous Leprosy form of Hansen's disease is called lepromatous leprosy. The tissues and mucous membranes contain billions of M. leprae, but there is almost no inflammatory response to them. The mucus of the nose and throat is loaded with the bacteria, which can readily be transmitted to others. Lymphocytes are present in the lesions but there is little or no evidence of macrophage activation.

In lepromatous leprosy, cell-mediated immunity to M. leprae is absent, although immunity and delayed hypersensitivity to other infectious agents are usually normal. Normal immune function tends to return when the disease is controlled by medication.

The very long generation time of this bacterium most likely accounts for the long incubation period of Hansen's disease, usually about 3 years (range 3 months to 20 years). ■ generation time, p. 85

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