The History of discovery
Mycobacterium leprae, the causative agent of leprosy, was discovered in 1874 by the Norwegian scientist G. Hansen.
Structure and Properties of Mycobacterium leprae
- M. leprae is similar to M. tuberculosis in many respects.
- They are acid-fast gram-positive pleomorphic bacteria that mostly appear as long straight or curved rods 1-8 μm in length. Granular, branching, and other forms also occur. These microorganisms don’t produce spores or flagella.
- The pathogens are enwrapped into a capsule-like layers made of glycolipids and mannosidase.
- M. leprae stain red by Ziehl-Neelsen method. They are determined intracellularly in tight bundles, resembling packets of cigars.
- The bacteria are not adapted to grow in artificial nutrient media. They are obligate intracellular parasites.
- M. leprae can propagate after inoculation into mouse footpad within 25-30 days. The most suitable model for bacterial culture in vivo is the experimental infection of armadillos, which produces high bacillary lepromatous leprosy.
- Biochemical properties of M. leprae are not fully investigated because of bacterial slow metabolism and absence of feasible methods for culturing.
- The bacteria pertain to microaerophils. They have the reduced number of enzymes in comparison with M. tuberculosis.
- M. leprae produces enzyme superoxide dismutase that protects it against phagocytosis.
Antigenic structure and virulence factors
- Bacterial antigenic structure, as well as virulence factor production, is also not completely elucidated. M. leprae contains antigenic polysaccharides and numerous lipids, including leprosinic oxy fatty acid, wax leprozine, and various phosphatides.
- Antigenic specificity of bacteria is related with phenolic glycolipid fraction PGL-1 of microbial cell wall.
- Toxic substances of bacteria are associated with microbial body and release upon its destruction.
- Glycolipid capsule-like layer protect M. leprae against phagocytosis. The enzyme superoxide dismutase inhibits respiratory burst in phagocytes.
- Phenolic glycolipid fraction PGL-1 suppresses the activity of dendritic cells and T lymphocytes and takes part in M. leprae binding to Schwann cells of myelinated nerve fibers.
- During infection bacteria cause the allergic sensitization of host with remarkable cellular immune suppression and demyelination of nerve tissue.
M. leprae shows similar resistance with M. tuberculosis and stays viable in tissues of human corpse for more than a year. Nevertheless, free bacterial cells rapidly lose viability in the environment.
Pathogenesis and Clinical Findings in Leprosy
- Leprosy is an anthroponotic torpid chronic disease.
- Due to the active strategy of treatment, the total number of patients with leprosy seriously decreased – from 805,000 persons in 1995 to about 175,000 affected individuals at the end of 2014 predominantly in Asia and Africa.
- People usually develop the disease after extremely long incubation period lasting from 3-5 years to several decades.
- Illness acquisition is possible only after close prolonged contact of a person with leprosy patient.
- It is generally considered that disease progression is strongly related with individual genetic predisposition. Natural resistance to leprosy is common and may cover about 95% of human population.
- Genetic mechanisms of the resistance are not well-elucidated. Probably, they are associated with genes controlling cellular immune response (antigen recognition, processing and presentation, cytokine production, microbial cell killing, etc.).
- The disease is transmitted via airborne or contact route through the nasopharynx epithelium or injured skin. Various fomites play a role of auxiliary vehicles in the disease transmission.
- M. leprae can persist only within living cells. The disease may be latent all over the life. Bacteria slowly disseminate throughout the body and affect skin, nasopharynx, larynx, eyes, peripheral nerves and other tissues. Microbial active propagation is possible in conditions of suppression of cellular immunity with inefficacy of phagocytosis.
- It is considered that M. leprae persist predominantly within demyelinated nervous tissue, where the bacteria are able to maintain favorable conditions for their survival.
- Within epineurium the bacteria target myelinating Schwann cells and macrophages and propagate. As the result, chronic granulomatous inflammation arises resulting in direct injury of peripheral nerves with their demyelination.
- Erythematous painless lesions with nodular infiltration appear in the skin. The damage of nerves is followed by paresthesia and polyneuritis. Trophic disorders lead to deep tissue lesions resulting in bone resorption. Sometimes it might be followed by phalanx self-amputations.
- Three main clinical forms of leprosy are observed: lepromatous, tuberculoid, and undifferentiated.
- WHO distinguishes multibacillary leprosy and paucibacillary leprosy.
- Lepromatous type of disease is characterized by malignant course of infection with active microbial propagation within myelinated nerve fibers that results in severe tissue lesions and neurologic disorders.
- The disease progression rests on the activation of suppressor immune cells and T helper 2 subsets. Together with deleterious effects of M. leprae itself (e.g., by the action of phenolic glycolipid PGL-1) it strongly inhibits cell-mediated immune response. This abrogates limitations for microbial growth.
- M. leprae in large amounts are determined in the sites of infection. Therefore, this clinical condition corresponds to multibacillary leprosy.
- The allergic skin test with lepromin (boiled extract of lepromatous node) is negative in this situation due to deep immune suppression.
- Tuberculoid type of the disease develops benign course with favorable prognosis. Skin lesions and peripheral nerves are involved in the process but only few or lack of bacteria can be found there (paucibacillary leprosy).
- Cell-mediated immunity is capable of controlling tuberculoid disease as T helper 1 cells remain active. They stimulate macrophages and dendritic cells that is followed by sufficient production of proinflammatory cytokines (IL-1, IL-12, IL-18, α-TNF, γ-interferon). The ongoing reactions of delayed hypersensitivity tackle the infection.
- Lepromin test is positive in this clinical condition.
- Undifferentiated type is usually related with the intermediate stage of the disease that may result in leprosy progression.
Laboratory Diagnosis of Leprosy
- Specimens from scrapings of nasal mucosa, skin lesions, lepromatous nodes and lymph node biopsies, patient’s sputum and ulcer discharges are used for examination.
- Microscopy is the basic method for laboratory diagnosis of leprosy. The slides are stained with Ziehl-Neelsen method. Intracellular bundles of acid-fast bacilli are observed.
- The detection of M. leprae is also performed by immunofluorescence.
- The advanced molecular tests for laboratory diagnosis of leprosy are based on PCR that detects microbial DNA.
- Allergic skin test with lepromin (Mitsuda reaction) is useful to distinguish lepromatous or tuberculoid type of the disease.
- Serological testing is of limited value due to the moderate titers of specific antibodies. Antibodies against PGL-1 are determined by ELISA.
Specific Treatment and Prophylaxis of Leprosy
- Recently WHO announced the Global Leprosy Strategy 2016–2020 under the common motto “Accelerating towards a leprosy-free world”. It has been stated that evident successes in leprosy management are essentially related to the availability of efficient disease treatment.
- Now MDT (or multidrug therapy) regimen is commonly used. It presumes the administration of sulfone drug dapsone, antimycobacterial agent rifampicin, and clofazimine.
- The course of therapy for multibacillary leprosy lasts for 12 months to provide complete elimination of pathogens.
- Prophylaxis is only non-specific, though numerous attempts of BCG vaccination were performed with contradictory results.
- Leprosy patients, who are active producers of mycobacteria, should be isolated and treated until complete clinical recovery.
- Healthy children need to be separated from sick parents and, if necessary, treated with antimicrobial drugs for disease chemoprophylaxis.