Leprosy agent

Morphology and Physiology

The bacterium Mycobacterium leprae (discovered by G.A. Hansen in 1874) belongs to the family Mycobacteriaceae. It is a straight or slightly curved rod that is acid- and alcohol-fast. The bacterium does not form true spores or capsules, but is protected by a microcapsule and a strong, rigid cell wall resistant to chemical agents and deformation. The microorganism's cytoplasm contains volutin granules and lipid inclusions.

In tissues, the pathogen demonstrates polymorphism: in addition to homogeneously stained forms, fragmented and granular variants may occur. When therapy is unsuccessful, spore-like bodies can form in the patient's body. Moreover, even after lysis, mycobacteria are able to preserve structures surrounded by a dense three-layer membrane that can potentially revert back into vegetative forms.

In smears stained using the Ziehl–Neelsen method, bacteria are found localized in the cytoplasm of host cells. There they form spherical clusters within which the rods are arranged strictly parallel to each other—this phenomenon is often referred to as the "cigar bundle" sign.

The leprosy pathogen is a strict aerobe. It metabolizes glucose and glycerol, but does not grow on artificial nutrient media. Its reproduction rate is extremely low—about 12 days are required for a single division. A critical physiological feature is the production of the enzyme O-diphenoloxidase. This enzyme oxidizes DOPA in human melanocytes, which disrupts pigment synthesis and leads to a characteristic clinical symptom—hypopigmentation of affected skin areas.

Epidemiology and pathogenicity factors

Leprosy is an anthroponotic infection with a low degree of contagiousness. The only source and reservoir of infection is a sick human. Transmission requires massive infection and prolonged, close contact with the patient.

Main transmission routes of the pathogen:

• Airborne (primary): bacteria are released into the environment with sputum and mucus during sneezing, coughing, or talking.
• Contact: transmission occurs through discharge from ulcers during the breakdown of lepromas, as well as through biological fluids (semen, blood).

For successful invasion and survival in the host organism, M. leprae uses a number of pathogenicity factors. A special fibronectin-binding protein ensures cell entry. Once inside, the mycobacterium effectively resists phagocytosis due to a lipid-rich microcapsule, a cell wall (which protects against lysosomal enzymes), specific wax (leprosin), and species-specific phenolic glycolipid (PGL-I). The pathogen's survival is also facilitated by genetic defects in the patient's own macrophages, causing the phagocytosis process to be incomplete.

Pathogenesis and clinical forms

The entry portals of the infection are the mucous membranes of the respiratory tract and damaged skin, while no visible changes occur at the site of primary introduction (no primary affect). Then dissemination of the pathogen throughout the body occurs via lymphohematogenous routes.

Leprosy mycobacteria are tropic to low-temperature tissues: the skin, nasal mucosa, and superficial nerves. The basis of nervous system damage is the selective binding of bacteria to the G-domain of laminin-2, a component of the basement membrane of Schwann cells. Since the phagocytic activity of these cells is extremely low, bacteria multiply inside them for years. Over time, pathogen antigens activate T-lymphocytes, triggering chronic inflammation. Edema develops within the perineurium, leading to ischemia, fibrosis, and axonal death. Clinically, this manifests as complete loss of pain, temperature, and tactile sensitivity.

The development of a specific clinical form depends on the state of the body's resistance:

1. Tuberculoid form: occurs with strong cellular immunity. It has a benign course. It manifests as hypopigmented spots, erythematous plaques, and loss of sensitivity. Histologically, epithelioid granulomas are detected, and the pathogen itself is extremely rare.
2. Lepromatous form: develops with low resistance. This is a malignant process with persistent bacteremia and high epidemiological danger. Abundant infiltrates and nodules (lepra) form on the skin, and the upper respiratory tract is affected. The rashes contain a huge number of mycobacteria.
3. Borderline forms: undifferentiated and borderline states that can eventually transform into one of the two main poles of the disease.

Diagnostics and treatment

Since M. leprae cannot be cultured in vitro, animals with low body temperature are used for experimental study: mice (inoculation into footpads via the Shepard method) and nine-banded armadillos.

In clinical practice, bacterioscopy is the basis of diagnostics. Materials include sputum, lymph node punctates, tissue fluid (skin scrapings taken from at least 6 sites, including earlobes and superciliary arches), and biopsies. The specimens are stained using Ziehl–Neelsen to search for intracellular clusters of acid-fast rods. Histological examination of skin biopsies not only confirms the diagnosis, but also serves as the main criterion for a patient's complete cure. Additional methods include PCR and ELISA (looking for antibodies to phenolic glycolipid).

For the differential diagnosis of forms and assessment of immune status, the lepromin test (a suspension of autoclaved bacteria isolated from armadillos) is performed. In the tuberculoid form, it is positive; in the lepromatous form, it is negative. The test is not suitable for confirming primary infection.

Etiotropic treatment for leprosy is always complex. Combinations of sulfones (dapsone), rifampicin, clofazimine, and fluoroquinolones are used. For paucibacillary forms, the course lasts from 6 months; for multibacillary forms, at least 2 years, until biopsies are completely cleared of the pathogen. There is no specific vaccine for leprosy, but the BCG vaccine has a certain protective effect in endemic regions.

Class and exam questions

What else to study on this topic

• Features of the immune response in tuberculoid and lepromatous forms of leprosy
• Experimental models of leprosy: nine-banded armadillos and the Shepard method
• Molecular mechanisms of mycobacterial interaction with Schwann cells
• Combination antibiotic therapy regimens for leprosy (WHO recommendations)

Other topics in the section "Irregular Gram-positive rods (Diphtheria, Mycobacteria/tuberculosis and leprosy, Actinomycetes, Nocardia, Bifidobacteria, Gardnerella, etc.)"

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