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Leprosy is a slow but potentially devastating disease caused by the microbe Mycobacterium leprae. The pseudonym Hansen's disease (HD) is a mark of recognition of the work done by the Dutch microbiologist Gerhard Hansen on its etiology.
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3D illustration of Mycobacterium leprae – the bacteria which causes leprosy.
Mycobacterium leprae is an acid-fast organism i.e., its cell wall contains large amounts of mycolic acid and waxes, among other complex lipids. This imparts a waxy consistency to the cell wall and enables it to resist decolorization following staining with carbol fuchsin, which otherwise gives the cytoplasm a red color.
This characteristic retention of the red color following application of acidified alcohol gives rise to the term acid-fast. M. leprae is a fastidious organism, making its culture very difficult to grow in vitro. In fact it took decades to find a suitable medium in which to culture the organism, which led to considerable delays in establishing the etiological role of M. leprae. In the US, it is chiefly found in the nine-banded armadillo.
It is highly contagious but produces few clinical cases due to the natural immunity of most human beings to the bacterium. Approximately 95 percent of human beings are thought to be genetically immune to this infection.
However, this figure may vary with respect to discrete population groups and with a prolonged generational history of exposure to the disease or the microbe. For example, the prevalence in Micronesia is much higher than among most other population groups. This may be due to lack of previous exposure, as well as to differences in the native susceptibility.
Host, environmental, and pathogen factors interact in a complex and poorly understood way in Hansen’s disease. In most cases the genetic variability and virulence of the pathogen are not noticeably different between different clinical forms of the disease.
In other words, the variation in the manifestations of leprosy is due to differences in the genetic make-up of the susceptible host, mediated by the differential activation of metabolic pathways by the microbe, along with Schwann cell reprogramming and individual-specific differences in the contribution of innate and adaptive immunity. Each case may therefore be thought of as unique.
Close contact with an infected person over a long duration is required for transmission to occur to a susceptible individual. Flugge droplets in nasal secretions are responsible for transmission, via inhalation. Other than the nasal secretion, skin ulcers, blood, breast milk, insect bites, or vertical transmission, may all act less commonly as routes of transmission.
Carrier states are also thought to exist and to be involved in leprosy transmission.
Risk factors include:
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M. leprae produces chronic infection chiefly of the peripheral nerves and the skin, but also of the eyes, mucous membranes, bones, and testes. Its infection manifests along a spectrum with tuberculoid leprosy being at one end and lepromatous leprosy at the other.
M. leprae is harbored in the myelinating Schwann cells of the axons in peripheral nerves, but in the skin it migrates to the keratinocytes, macrophages, and histiocytes. Its attachment to the Schwann cells is based on the presence of specific adhesion molecules in the basal lamina of the cell membrane and ErbB2 or alpha-dystroglycan receptors on the cell surface. The bacillus enters the host cell and signals its dedifferentiation, causing it to take on the characteristics of immature cells. These foster bacillary proliferation.
The Schwann cell is not only dedifferentiated but transformed into something closely resembling a stem cell, which can then become a mesenchymal cell migrating to other parts of the body to spread the microbe. Or on the other hand, it could produce an inflammatory reaction resulting in granuloma formation, which then becomes a center from which repeated waves of bacilli invade the rest of the body.
Eventually axonal conduction is impaired and demyelination occurs, leading to loss of sensation in the affected limb. This results in repeated minor or major injuries and deformity, and ultimately permanent disability. In addition to this deadly cycle of nervous degeneration following M. leprae infection, another potent cause of the sensory loss is the periodic immune flare-ups called leprosy reactions, which further increase the inflammatory damage to the peripheral nerves.
Leprosy reactions are of two types, the type 1 (reversal reactions) and the type 2 reactions (erythema nodosum leprosum). They may precede, be concurrent with, or follow treatment. They are treated with corticosteroids, thalidomide, TNF inhibitors, or T cell inhibitors, among others, depending on the clinical signs and severity. They must be promptly diagnosed and treated to prevent further worsening of the sequelae, as they represent a drastic increase in immunologically-mediated inflammatory reactions around the peripheral nerves, leading to nerve compression and damage.
M. lepromatosis is a recently discovered species which was found in patients who had diffuse leprosy of Lucio and Latapi. This refers to a widespread form of HD associated with endothelial cell injury and necrotizing lesions.