4. Pathogenesis of leprosy

Kalimantan, South Kalimantan, and East Java, leprosy remains prevalent. Tangerang District Health apparatuses in Banten province recently conducted a leprosy census and found that as many as 397 patients with leprosy were in need of serious attention. Leprosy remains a largely neglected disease, especially in the rural areas of the country, where little is known about it, and many suffer from the stigma and lack of knowledge surrounding the disease. East Java provincial Health Office Chief Dr. Harsono remarked in Surabaya that the local government would continue to take steps to reduce the number of leprosy patients and hoped that the figure will come down to less than one patient per 10,000 population. Leprosy has been around since the beginning of time, often surrounded by terrifying, negative stigma, and tales of leprosy patients being shunned as outcasts [9]. The 5-year strategy was launched previously: Strategy "The last impetus for eliminating leprosy as a public health problem" (2000–2005) aimed at eliminating leprosy as a public health problem at the country level. This is data-making and the general public, communications, and campaigns. All countries with a population of one million or more have achieved leprosy eradication as a

Two successive strategies—the "Global strategy to further reduce leprosy burden and maintain leprosy control activities" (Period of planning stage: 2006–2010) and "Improved global strategy to further reduce the burden of disease due to leprosy" (Period of planning stage: 2011–2015)—maintaining an emphasis on reducing disease burden by focusing on sustainability through integration. They have moved from the target of "elimination" in terms of the prevalence of disease to the target, which emphasizes the decline in the number of new cases

Leprosy has been linked to stigma throughout history [10]. Stigma manifestations, including self-stigma, social exclusion, and discrimination, although now more subtle with less exile, remain a reality for many affected people [12]. To help leprosy services become more responsive to problems surrounding leprosy-related stigma and reduce its impact, it is necessary to understand the stigma from the perspective of affected people and their family members. Also the views of key people in society, such as neighbors, teachers, religious leaders, and health workers, should be considered. The "human face of leprosy" edited by Gokhale and Sohoni in

Factors to consider are pathogenesis of germs, mode of transmission, environmental conditions, and genetic variants associated with susceptibility, immune change, and the possibility of reservoirs outside humans. Today's leprosy differs with environmental conditions, genetic variants associated with susceptibility, immune change, and the possibility of reservoirs outside humans. Today's leprosy differs from the leprosy of the past, but yet there are still many things that are not immediately known, so it is still a broad socioeconomic and challenge for scientists to solve. Research by Bakker et al. found that the risk factors of leprosy in Indonesia

with G2D to promote early detection and reduction of transmission [11].

public health problem at the national level [10].

8 Current Topics in Tropical Emerging Diseases and Travel Medicine

1999 has emphasized the need for such stories [13].

3. Risk factor

Leprosy onset is insidious. It is about the nerves, skin, and eyes. It can also attack the mucosa (mouth, nose, and pharynx), testes, kidneys, smooth/smooth muscle, reticulo-endothelial system, and vascular endothelium. Germs enter the body usually through the respiratory system. It has low pathogenicity, and only a small percentage of infected people show signs of the disease. Although infected, most of the population do not develop the disease. Upon entering the body, the bacilli will migrate to the neural network and enter Schwann cells. Bacteria can also be found in macrophages, muscle cells, and endothelial cells of the blood vessels. After entering Schwann/macrophage cells, the fate of the bacteria depends on the resistance of the infected individual to the infecting organism. Bacilli began to proliferate slowly (about 12–14 days for one bacteria split into two) inside the cell, released from the crushed cell and into the unaffected cells. Until this stage, people remain free from signs and symptoms of leprosy. When bacilli proliferate, the bacterial load increases in the body, and the infection is recognized by the immunological system. Lymphocytes and histiocytes (macrophages) invade infected tissue. At this stage, clinical manifestations may appear as nerve involvement with impaired sensation or skin patches. If not diagnosed and treated in the early stages, further progression of the disease is determined by the strength of the patient's immune response [14].

In people with strong cell-mediated immunity (CMI), granuloma formation occurs in skin nerves, and cutaneous nerve is enlarged and damaged. Often only a few infiltrated nerves are inflamed, but the inflammation inside the epineurium causes compression and destruction of the unmyelinated sensory and autonomous fibers. Myelinated motor fibers are affected last to produce motor damage. Severe inflammation can cause necrosis in the nerve. Clinical manifestations of sensory loss occur when nearly 30% of sensory fibers are destroyed. A good CMI manages to limit disease to nerve Schwann cells that result in pure leprosy. M. leprae can escape from nerves to adjacent skin all the time and causes classic skin lesions. Areas of the skin with relatively higher temperatures such as axilla, groin, perineum, and hairy scalp are usually spared. But in people with immature cell-cell immunity, the bacilli that enter Schwann cells multiply uncontrollably and destroy the nerves. Also, the bacilli released by infected and destroyed cells are swallowed by histiocytes. Histiocytes with bacilli in it become wandering macrophages. Bacilli multiply in this macrophage and run into other tissues through blood, lymph, or tissue fluid [14].

The modulation of lipid metabolism and reprogramming of mature Schwann cells have been suggested as a mechanism used by M. leprae to spread disease. New markers associated with local disease, dissemination, or occurrence leprosy reaction events include human interferon, CD163, microRNA-21, NOD2, galectin-3, and toll-like receptors. The role of keratinocytes other than macrophages is interesting to understand in the pathogenesis of leprosy. Adaptive immune reports focus on the role of regulatory T cells and cytokines secreted by T helper cells in leprosy. Finally, a newly identified species named M. lepromatosis has been detected in patients with severe leprosy and erythema nodosum leprosum [8].

M. leprae has a predilection for Schwann cells, for specific binding to the G domain of the laminin alpha-2 chain, which is expressed specifically in the basal lamina of peripheral nerves [19]. Development of the disease depends on the immune status of patients. The role of genetics, associated with a susceptibility locus at chromosome 10p13, near the mannose receptor on the surface macrophages, is important in the phagocytosis. The other role of major histocompatibility complex (class II HLA) genes at chromosome 6 has been implicated in the clinical type of patient leprosy. The lepromatous form affects the skin and peripheral nerve, causing well-defined infiltrated plaques that are annular or ovoid form. Immunohistochemical findings in skin biopsies show mainly interleukins 4 and 10. The immune response to M. leprae is variable and gives rise to spontaneously changing clinical manifestations that may present

Leprosy: The Ancient and Stubborn Disease http://dx.doi.org/10.5772/intechopen.79984 11

The steps in the transmission of the disease are not entirely clear. However, it is acceptable that the mycobacterium reservoir is exclusively human, and it is most often transmitted through the spread of basil aerosol. In many cases, the infection appears to occur during childhood, with an incubation period ranging from 6 months to several years. Rarely, very long incubation periods of up to 40 years have been reported, although infection rates in adults with close contact with infected individuals (e.g. spouse) are as low as 5% even in long-term investigations [20].

Leprosy usually begins as an indeterminate form that can heal spontaneously, remain unchanged for long periods, or progress to a more severe form. About 95% of contact with the bacillus will result in spontaneous resolution without the development of clinical symptoms. This initial indefinite form can produce patches or macules of the skin, which is not clear with little hypopigmentation. In parallel, such patches may coincide with hypoesthesia of the corresponding skin nerve. If the disease develops, tuberculoid leprosy can develop as long as the host immune response is preserved enough. At this stage, rapid skin sensation loss due to severe neurological damage can occur, as well as local paralysis, loss of sweat and sebaceous glands, and hair loss. The skin shows macular lesions with significant hypopigmentation; peripheral nerves are infiltrated and may present as thick subcutaneous bundles. Secondary symptoms include bruised skin under hypoesthesia due to local external damage and super-

The lepromatous stage occurs in individuals with poor immune reactions. Clinically, this is the most severe form and can lead to mutilation. Skin lesions may appear as macules, papules, or plaques with hypopigmentation. The most affected areas are the ears, the central face, the fingers, and toes, but the distal extremities, such as the extensor surfaces of the thighs and forearms, can also be affected. Severe skin infiltrations in the peri-nasal and periorbital areas lead to "facies leonine" or lion face, associated with loss of eyelashes and lateral eyebrows ("facies leprosy"). Often, blindness can occur when the eye is exposed. Osseous resorption of the nostrils and destruction of the bridge of the nose result in severe facial mutilation. The Mycobacterium leprae affected throat can cause a distinctive hoarseness. In fact, all other body areas can also be affected, leading to varying clinical features. The fourth stage, called the borderline stage, also exists, which is somewhat intermediate between tuberculoid and lepromatous stages in clinical symptoms. Considering the various clinical symptoms, especially the early stages and stages of minor illness, leprosy can easily be confused with various other diseases. This is often important for historical

as type 1 or 2 leprosy reactions [17].

infection with poor healing ulcers [21].
