Mycobacterium leprae

Mycobacterium leprae was discovered by Hansen in 1874 (Hansen's bacillus).

Mycobacterium leprae (from Greek mykes = fungus, bakterion = rod) and the recently discovered Mycobacterium lepromatosis (Han et al., 2008) are the causative agents of leprosy in humans and animals (Schilling et al. 2019; Tió-Coma et al., 2019). Leprosy is a complex infectious disease that often leads to severe, lifelong disability and is still a serious health threat in low- and middle-income countries (World Health Organization 2019).

Bacteria of the species Mycobacterium leprae have a curved, rod-shaped form. They are immobile and do not form spores. Under tropical conditions, the bacteria can survive outside the human body for up to 9 days. In the body, they behave similarly to Mycobacterium tuberculosis. They are obligatory intracellular and need about 10 to 14 days to divide (E. coli bacteria need only about 20 minutes for this). The organism's defence consists exclusively of a T-cell-mediated immune reaction. Histopathologically, the infection manifests itself in the organization of epithelioid cell granulomas.

Due to its enzymatic composition, the bacterium has a unique tropism for peripheral nerves, skin and mucosal membranes and is thus particularly well able to infect and multiply in these tissues. M. leprae can be detected mainly in the nasal secretions of infected persons.

Prevalences: Despite effective medications, approximately 210,000 new cases are still diagnosed annually, and this incidence rate has remained stable over the past decade (World Health Organization, 2019). Leprosy diseases are favoured by poor social living conditions, as these are often also associated with unfavourable hygienic conditions. Thus, leprosy cases occur mainly in rural areas of developing countries in Southeast Asia, China, South America and tropical Africa.

Transmission: The portal of entry of Mycobacterium leprae into the human organism has not yet been identified beyond doubt. However, the main reservoir of Mycobacterium appears to be humans.Aerosol transmission via the respiratory tract is generally accepted as the most likely route of bacterial dissemination. In addition to bacterial exposure, other risk factors have been associated with the development of leprosy, such as genetic polymorphisms, clinical type of leprosy, immunosuppression, and nutritional factors (Dwivedi et al.2019). Zoonotic transmission by infected armadillos has been reported in the literature.

Latency: There are significant differences in the incidence of latent and apparant infections on the one hand and non-contagious and contagious infections on the other. Latent infections may persist asymptomatically for years or possibly even decades, but they may also pass into spontaneous healing at any time. If they lead to manifest disease, the average incubation period is about four years. In endemic areas, considerable parts of the population are infected with the pathogen, whereby even the manifest diseases in the early stages heal spontaneously to a high percentage. The decisive factor is the cell-mediated immunocompetence of the infected person. Only a relevant immunological deficiency paves the way for active infection.

In the common staining according to Ziehl-Neelsen, the initially used red staining agent carbolfuchsin cannot be washed out by hydrochloric or sulfuric acid, other substrates are subsequently stained with methylene blue. Mycobacterium leprae has a Gram-positive cell wall composed of multilayered peptidoglycans. The peptidoglycan layer contains a polymer of arabinose and galactose (arabino-galactan), to which various long-chain lipids, the mycolic acids, are bound. This peculiarity means that Mycobacterium leprae (and other mycobacteria) cannot be stained with the usual Gram stain, but that dyes penetrate the bacteria only through the action of heat and phenol. Accordingly, mycobacteria are also more difficult to decolorize; penetrated dye is not washed out again even by treatment with a mixture of acid and alcohol.

M. leprae is an obligate parasite that can apparently survive outside the human body for up to ten days. It cannot be grown on any known culture medium, but can be grown in the paw of the immunosuppressed mouse and in the nine-banded armadillo, the armadillo. The armadillo, as well as the body regions preferentially affected in humans and mice, are characterized by a comparatively low temperature, which favors the growth of M. leprae. The germ divides only about every twelve days and does not form spores.

The incubation period is months to years

The following clinical forms are distinguished (see below Leprosy):

• Indeterminate leprosy (L.indeterminata)
• Lepromatous leprosy (L.lepromatosa)
• Tuberculoid leprosy
• Bordeline leprosy

Cultivation is not possible. Therefore, the clinical findings and the detection of the acid-fast rods are decisive.

Microscopic detection in skin or mucous membrane scrapings after staining according to n. Ziehl-Neelsen.

Detection of M. leprae-specific DNA from skin samples using PCR diagnostics confirms the diagnosis.

The assessment of the amount of mycobacteria is important for the prognosis. The evaluation is made as "multibacillary", pathogen-rich (therapy duration over 12 months) and "paucibacillary", pathogen-poor (therapy duration 6 months).

1. Braet S et al. (2018) The repetitive element RLEP is a highly specific target for detection of Mycobacterium leprae. J Clin Microbiol 56:e01924-17.
2. Cole ST et al (2001) Massive gene decay in the leprosy bacillus. Nature 409: 1007-1011.
3. Donoghue H D (2019). Tuberculosis and leprosy associated with historical human population movements in Europe and beyond - an overview based on mycobacterial ancient DNA. Ann Hum Biol 46: 120-128.
4. Donoghue H D et al (2001). PCR primers that can detect low levels of Mycobacterium leprae DNA. J Med Microbiol 50: 177-182.
5. Dwivedi VP et al. (2019) Diet and nutrition: an important risk factor in leprosy. Microb. Pathog 137:103714.
6. Kumar B et al.(2017) "Clinical diagnosis of leprosy," in International Textbook of Leprosy, eds D. M. Scollard and T. P. Gills. www.internationaltextbookofleprosy.org (accessed March 2021).
7. Ridley DS et al. (1966) Classification of leprosy according to immunity. A five-group system. Int J Lepr Other Mycobact. Dis 34: 255-273.
8. Schilling AK et al.(2019) Detection of humoral immunity to mycobacteria causing leprosy in Eurasian red squirrels (Sciurus vulgaris) using a quantitative rapid test. Eur. J. Wildl Res. 65:49.
9. Singh P et al.(2011) Mycobacterium leprae: genes, pseudogenes and genetic diversity. Future Microbiol 6: 57-71
10. Tió-Coma M et al. (2019) Lack of evidence for the presence of leprosy bacilli in red squirrels from North-West Europe. Transbound Emerg Dis 67: 1032-1034.
11. Tió-Coma et al. (2019) Detection of Mycobacterium leprae DNA in soil: multiple needles in the haystack. Sci. Rep. 9:3165.
12. World Health Organization (2017). A Guide for Surveillance of Antimicrobial Resistance in Leprosy. New Delhi: World Health Organization, Region Office for South-East Asia.
13. World Health Organization (2019). Global leprosy update, 2018: moving towards a leprosy-free world. Weekly Epidemiol Rec 94: 389-412.