**2. History and epidemiology**

M. leprae is an intracellular microorganism and an acid-resistant bacilli leading to a loss of sensibility, innervation, intraepidermal impairment and lesions due to the absence of myelin in Schwann cells. If the bacilli are numerous, they can be grouped in parallel or arranged in parallel.

M. leprae has high infectivity and low pathogenicity. The incubation period is from 2 to 7 years.

An individual is infected by inhalation of infectious aerosol or through the skin while contacting with nasal secretions and/or skin changes of the infected individual.

Children are more susceptible to leprosy than adults. Due to the slow proliferation of leprosy (the time of one generation is 14 days), the incubation period of the disease is quite prolonged (2–5 years).

Due to infiltration of the peripheral nerves, neuritis, anesthesia, trophic ulcerations, muscle atrophy and bone resorption occur.

### **3. Basic scientific considerations and pathology**

Leprosy is an infectious neurodegenerative disorder of the peripheral nervous system. Thus, leprosy is the major cause of human disability due to neurological damage.

To this date, M. leprae has not been cultivated on artificial nutrients.

Nerve injury-associated tissue damage is the most prominent clinical consequence of leprosy.

In the process of leprosy-associated neuropathy, the presence of bacilli in nerve endings and Schwann cells induces a response mediated by macrophages and other cells that eventually leads to the appearance of immune-mediated lesions.

The most important cytokines are TNF-α, IL-6, IL-17 that are involved in the progression of neural lesions (**Figure 3**).

According to Antunes et al., it was concluded that in the individuals with neuritic leprosy, NGF-R immunoexpression was lower (nerve fiber, Schwann cells) than in control group (normal individuals). In the leprosy group, hypoesthesia was associated with decreased expression of NGF-R and PGP (protein gene product) 9.5.

TrkA receptors are detected in subepidermal fibers. TrkA receptor messenger RNA is produced in the skin. NGF are also present in keratinocytes and are in correlation with deficient thermal sensation [3].

NGF levels are depleted in nerve and skin lesions in leprosy the loss of NGFdependent nociceptive fibers in damaged skin. An additional cause of decreased NGF is an impaired interaction between keratinocytes and nerves in affected skin.

**Figure 3.** *Pathogenesis of leprosy [4].*

Higher levels of NGF are observed in the lepromatous forms, while lower NGF levels are present in tuberculoid forms.

High levels of NGF are associated with lepromatous and decreased levels are associated with tuberculoid forms [5].
