Morphology and Physiology
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 lacks true spores and capsules, but it is protected by a microcapsule and a robust, rigid cell wall resistant to chemical agents and deformation. The cytoplasm contains volutin granules and lipid inclusions.
In tissues, the pathogen exhibits polymorphism: alongside uniformly stained forms, fragmented and granular variants may be seen. In cases of unsuccessful therapy, spore-like bodies can form within the host. Furthermore, even after lysis, mycobacteria can retain structures surrounded by a dense trilaminar membrane that have the potential to revert to vegetative forms.
In Ziehl-Neelsen-stained smears, the bacteria are found localized within the cytoplasm of host cells. There, they form spherical clusters where the rods lie strictly parallel to one another—a phenomenon often referred to as the "cigar packet" appearance.
The leprosy bacillus is an obligate aerobe. It metabolizes glucose and glycerol, but it does not grow on artificial nutrient media. Its replication rate is extremely slow, with a single division taking about 12 days. A crucial physiological feature is the production of the enzyme O-diphenoloxidase. This enzyme oxidizes DOPA in human melanocytes, disrupting pigment synthesis and leading to a characteristic clinical sign: hypopigmentation of affected skin areas.
Epidemiology and Pathogenicity Factors
Leprosy is an anthroponotic infection with a low degree of contagiousness. The sole source and reservoir of infection is an infected human. Transmission requires massive exposure and prolonged, close contact with a patient.
Main routes of transmission:
- Aerogenic (primary): bacteria are released into the environment with sputum and nasal mucus during sneezing, coughing, or speaking.
- Contact: transmission occurs via discharge from ulcerating lepromas, as well as through bodily fluids (semen, blood).
To successfully invade and survive within the host organism, M. leprae utilizes several pathogenicity factors. A special fibronectin-binding protein mediates cell entry. Once inside, the mycobacterium effectively resists phagocytosis due to a lipid-rich microcapsule, a complex cell wall (which protects against lysosomal enzymes), specific wax components (leprosin), and species-specific phenolic glycolipid-1 (PGL-1). The pathogen's survival is also facilitated by genetic defects in the patient's macrophages, rendering the phagocytic process incomplete.
Pathogenesis and Clinical Forms
The portal of entry consists of the mucous membranes of the upper respiratory tract and damaged skin, with no visible changes occurring at the primary site of inoculation (no primary affect). The pathogen then disseminates throughout the body via the lymphohematogenous route.
M. leprae exhibits a strong tropism for cooler tissues: the skin, nasal mucosa, and superficial nerves. The basis of nervous system involvement is the selective binding of bacteria to the G-domain of laminin-2, a component of the basal lamina of Schwann cells. Because the phagocytic activity of these cells is extremely low, bacteria replicate 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 a complete loss of pain, temperature, and tactile sensitivity.
The development of a specific clinical form depends on the host's immune resistance:
- Tuberculoid leprosy: occurs in the presence of strong cell-mediated immunity. It has a benign course and presents with hypopigmented macules, erythematous plaques, and sensory loss. Histologically, epithelioid granulomas are found, while the pathogen itself is extremely rare.
- Lepromatous leprosy: develops when resistance is low. This is a malignant process characterized by persistent bacteremia and high epidemiological risk. Extensive infiltrates and lepromas form on the skin, and the upper respiratory tract is affected. Lesions contain an immense number of mycobacteria.
- Borderline forms: undifferentiated and intermediate states that may eventually evolve toward either of the two main polar forms of the disease.
Diagnosis and Treatment
Because M. leprae cannot be cultured in vitro, animals with lower body temperatures are used for experimental study: mice (inoculated in the footpads via the Shepard method) and nine-banded armadillos.
In clinical practice, the cornerstone of diagnosis is bacterioscopy. Samples include sputum, lymph node aspirates, and tissue fluid (skin slit smears taken from at least 6 sites, including the earlobes and eyebrows) along with biopsies. Specimens are stained using the Ziehl-Neelsen technique to detect intracellular clusters of acid-fast bacilli. Histological examination of skin biopsies not only confirms the diagnosis but also serves as the primary criterion for complete patient cure. Additional methods include PCR and ELISA (detecting antibodies to phenolic glycolipid).
For differential diagnosis of clinical forms and assessment of immune status, the lepromin test (a suspension of autoclaved bacteria harvested from armadillos) is performed. It is positive in tuberculoid leprosy and negative in lepromatous leprosy. This test is not suitable for confirming primary infection.
Specific treatment for leprosy is always multidrug therapy. Combinations of sulfones (dapsone), rifampicin, clofazimine, and fluoroquinolones are used. For paucibacillary forms, the course lasts at least 6 months; for multibacillary forms, it lasts at least 2 years, until skin biopsies are completely cleared of the pathogen. There is no specific vaccine against leprosy, though the BCG vaccine confers some cross-protective effect in endemic regions.