Leprosy

Leprosy is a chronic infectious disease caused by Mycobacterium leprae (Hansen's bacillus). The disease is not highly contagious (less than 1% of the population exposed to it becomes infected) and has a long incubation period (1–8 years). It is treatable, but there is no vaccine for it. Between 500 000 and 700 000 new cases are reported each year.

History
The Bible already writes about leprosy. Leprosy was known in ancient China, India, and Egypt. It is a disease that appeared in ancient times. The skin was soaking wet and there was a strong smell of festering wounds. Currently, this disease still occurs. It is estimated that 10-11 million people currently suffer from leprosy, mainly in Central Africa and Southeast Asia, but cases are also known from Southern Europe, especially Spain and also from Romania. It has been present in Romania since at least the 1950s, but it was kept secret by the Ceauşescu regime.

Basic distribution
There are two basic forms of leprosy – nervous (Lepromatous leprosy - LL) and cutaneous or nodular (Tuberculoid leprosy - TT). Most patients have symptoms of both forms (borderline forms are described: borderline tuberculoid - BT, borderline-borderline - BB and borderline lepromatous – BL forms). All variants eventually result in damage to the peripheral nerves in the extremities, causing loss of both sensory and motor function of the nerves. Research into this disease has been hampered by the fact that leprosy practically only affects humans (the other infectable species include only armadillos and three types of monkeys - chimpanzee, smoky mangabey and cynomolgus macaque), and also by the fact that the bacteria M. leprae cannot succeed in "extreme" conditions) be cultured in vitro. Armadillos and immunocompromised mice are used for research purposes. The genome of M. leprae was one of the first to be sequenced at the beginning of the 21st century.
 * The cutaneous form is characterized by a rapid, but time-delayed, immune response in the skin and nerves mediated by T-helper 1 (Th1) cells and hypersensitivity to M. leprae antigens
 * In the neural form, T-helper 2 (Th2) cells are active and there is an inability to respond to M. leprae antigens, so there is an abundant presence of this bacterium in the skin and nerves. Patients with this form, who are treated with antibiotics, are often (50% of cases) affected by inflammation of the subcutaneous tissue (or fat cells), in which hard, red, painful foci with a diameter of 1-5 cm appear ( erythema nodosum leprosum - ENL).

Manifestations and consequences
Leprosy usually does not show any significant symptoms and is also not highly contagious in most of its stages. The exception is the cutaneous formwhich producesulcerson the skin which tend to behighly infectious. Under unfavorable circumstances, a destructive form of leprosy may develop and endanger the patient's life. Leprosy mainly attacks Schwann cells and macrophages in the peripheral nervous system. It destroys the human immune system and causes disfigurement in the limbs and face. The skin and parts of the limbs remain numb. Lesions form on the skin (arms, legs, testicles) that look like an ulcer. The sebaceous glands stop working, the skin cracks. There is a violation of the integrity of the skin, which creates an entrance gate for infection. Due to the fact that hearing is impaired, the sufferer does not feel high temperature, e.g. fires caused burns in the Middle Ages. Another consequence of leprosy is blindness or impaired vision. The eyelid stops moving and the eye remains open.

Skin form
It manifests itself as a reddening of a part of the skin, most often in the face. This area is often symmetrical and appears around the nose, gradually darkeningto a gray-black color while its center fades, eventually being replaced by a white patch that resembles vitiligo. Lepromas begin to form in the affected part. This is often accompanied by fever and swelling of the local lymph nodes. Lepromas are formed not only on the face, but also on the limbs, where there is a loss of sensitivity in the affected areas - theis is why the skin is easily injured, ulcerated and necrosis occurs. As these nodules grow, they change the appearance of the face (called facies leonina or leontiasis).

Nerve form
It starts with the same rash, but the peripheral nervesin the trunk and limbs are also affected, where palpable lumps are formed. Over time, hyperesthesia develops, which is later replaced by anesthesia, first for heat and pain, and later for touch. Paralysis and skeletal muscle atrophy appear. In rare cases, lepromas also appear in internal organs (mainly lungs and spleen). The spleen is often enlarged due to the presence of amyloid.

Diagnostics

 * Lepromin test


 * It is not used to diagnose leprosy, but to distinguish whether the patient is affected by the LL or TT form. The application consists of a subcutaneous injection of a suspension of whole autoclaved (heat-killed) bacteria. If a granulomatous reaction develops in the skin after 4 weeks, it is a TT form ( APCs and T-lymphocytes reaction). The negative reaction is associated with the LL form (APC and T-lymphocytes do not react). As already said, this test is not used for diagnosis, because even a healthy person can have a positive reaction to the lepromin test.


 * Bacteria were used for this test directly from human lepromas, today they are obtained from infected armadillos. Currently, work is being done to identify protein antigens that would be used as reagents instead of whole bacteria, but none that are specific or sensitive enough have yet been found.

Skin biopsy, smear (possibly nerve biopsy)


 * Skin biopsy and subsequent histological analysis still plays an irreplaceable role in the diagnosis of leprosy. Classical hematoxylin-eosin staining and carbolfuchsin staining are used.


 * PCR

Complementary tests include a blood count, a liver and kidney function test.

Treatment
Until 1871, when the causative agent of the disease was discovered by the Norwegian microbiologist G. H. Armauer Hansen, the disease was believed to be either hereditary or a punishment from God. The sick (so-called lepers) were considered unclean and were concentrated in leprosariums. Since the description of this bacterium, the search for a treatment has begun. In the first half of the 20th century, chaulmoogra nut oil (a type of tree) was used by injection into the skin, but the effectiveness was debatable. In 1941, the drug Promin began to be used, which, although effective, required significant doses of anesthetics. Another drug, Dapsone, came on the market in the 1950s, but soon (1960-1970) bacteria developed resistance to it. Around 1970, they switched to a combination of three ATB (dapsone, rifampicin and clofazimine [Lamprene]) and this concept is still used today.

Etiology
As already stated, the causative agent of leprosy is Mycobacterium leprae, a non-motile, microaerophilic, non-sporulating, Gram-positive, acid-fast bacillus. The bacterium is contained in lepromas (nodules forming in the affected skin) intracellularly.

The route of infection is still not completely clear, but the mucous membrane of the nasopharynx and the skin are most often mentioned. Transmission by water has also been described. The source of infection is decayed ulcers, nasal mucus or stools of the sick person. Long-term close contact is necessary for transmission, so children are most at risk. The bacterium thrives best at temperatures lower than body temperature - therefore it mainly attacks the skin and peripheral nerves.

In the 1970s, at least two genes were hypothesized to control the immune response to leprosy and were later supported by subsequent research. Today, there is sufficient evidence for the existence of various genes controlling the immune response against M. leprae. This reaction is carried out on 2 levels. The first "package" of genes controls the monocyte mediated innate immune response. If this innate immunity is not effective enough, the infection takes root.

Subsequently, a second set of genes sets in that controls specific cellular immunity (antigen presenting cells (APC) and T-lymphocytes) and possibly delayed hypersensitivity to M. leprae antigens.

If leprosy has already stabilized in the body, what form of leprosy develops depends on the "quality" of the cellular immune response. If T-lymphocyte-mediated immunity is effective, a less severe form of TT develops, manifesting as white patches on the skin. This form can heal on its own. If this immunity is less "powerful", a more severe LL type of leprosy is usually manifested, in which symmetrical skin lesions, nodules, plaques, thinned dermis and frequent involvement of the nasal mucosa (bleeding) appear.

There are known cases where one family member has leprosy, but other close relatives do not get infected because they have a "good ability" to fight the infection.

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