leprosy.pptx

ok

1. Lepr o sy i s an infec t ious disea s e t h at causes p a i n f u l whi t e areas on th e sk i n and can dest r oy n erves and fle s h (epithelium). Leprosy (Hansen's disease) is a nonfatal, chronic infectious disease caused by Mycobacterium leprae , whose clinical manifestations are largely confined to the skin, peripheral nervous system, upper respiratory tract, eyes, and testes. The unique tropism of M. leprae for peripheral nerves and certain immunologically mediated reactional states are the major causes of morbidity in leprosy.

2. It occurs in two forms: Lepromatous leprosy and  the skin, mucous membrane, etc are involved. Tuberculoid leprosy  infiltration of nerves results in subcutaneous nodules, anaesthesia and bleaching of the skin , trophic ulcers, and various deformities. Between these two forms there are borderline leprosy and indeterminate leprosy.

3. For the purpose of convenience in the treatment , leprosy has been divided into two forms: Multibacillary leprosy: It i s th e infectious fo r m o f th e disease and i n c ludes lepromatous and borderline cases. Paucibacillary leprosy: It i s th e no n-infec t i o u s fo r m and i n cludes smear negative, intermediate, tuberculoid and borderline cases.

4. The disease is endemic in areas with hot and moist climates and in poor tropical countries . According to the WHO, 8 countries—India, China, Nepal, Brazil, Indonesia, Myanmar (Burma), Madagascar and Nigeria, together constitute about 80% of leprosy cases, of which India accounts for one-third of all registered leprosy cases globally. In India, the disease is seen more commonly in regions like Tamil Nadu, Bihar, Pondicherry, Andhra Pradesh, Orissa, West Bengal and Assam. Very few cases are now seen in Europe and the United States.

5. It is caused by Mycobacterium leprae. It affects mainly peripheral nerves. It also a f fects the sk i n, m u s cle s , eye, b o nes, te s tes a nd internal organs.

6. Leprosy is a slow communicable disease and the incubation period between first exposure and appearance of signs of the disease varies from 2 to 20 years (average about 3 years). The infectivity may be from the following sources: 1. Direct contact with untreated leprosy patients who shed numerous bacilli from damaged skin, nasal secretions, mucous membrane of mouth and hair follicles. 2. Materno-foetal t ransmission across the placenta. 3. Transmission from milk of leprosy patient to the infant.

7. Schwann cells (SCs) are a major target for infection by M. leprae leading to injury of the nerve , demyelination , and consequent disability and loss of axonal conductance. M. leprae can invade SCs by a specific laminin-binding protein. Macrophages are one of the most abundant host cells to come in contact with mycobacteria. Phagocytosis of M. leprae by monocyte-derived macrophages can be mediated by complement receptors CR1 (CD35), CR3 (CD11b/CD18), and CR4 (CD11c/CD18).

8. Leprosy is associated with an evolution from asymmetric localized macules (discolored area of skin) and plaques to nodular and indurated symmetric generalized skin manifestations, and increasing bacterial load, and loss of M. leprae– specific cellular immunity. Distinguishing dermatopathologic characteristics include the number of lymphocytes, giant cells, and AFB (Acid-Fast Bacillus) as well as the nature of epithelioid cell differentiation.

9. The immune response in leprosy is T cell-mediated delayed hypersensitivity (type IV reaction). M. leprae do not produce any toxins but instead the damage to tissues is immune-mediated. This is due to following peculiar aspects in immunology of leprosy:

10. 1. Antigens of leprosy bacilli. The bacterial cell wall contains large amount of M. leprae- specific phenolic glycolipid (PGL-1) and another surface antigen, lipo-arabinomannan (LAMN). These antigens of the bacilli determine the immune reaction of host lymphocytes and macrophages. Another unique feature of leprosy bacilli is invasion in peripheral nerves which is due to the binding of trisaccharide of M. leprae to basal lamina of Schwann cells

11. 2. Genotype of the host. Genetic composition of the host as known by MHC class (or HLA type) determines which antigen of leprosy bacilli shall interact with host immune cells. Accordingly, the host response to the leprosy bacilli in different individuals is variable.

12. 3. T cell response. There i s va r iation i n T cell res p onse i n di f f ere n t i n divid u a ls infected with leprosy bacilli: i) activation of CD4+ T cells qnd CD8+ T cells. ii) CD4+ T cells in lepra bacilli infected persons act not only as helper and promoter cells but also assume the role of cytotoxicity. iii) The two subpopulations of CD4+ T cells (or T helper cells)—TH 1 cells and TH 2 cells, elaborate different types of cytokines in response to stimuli from the lepra bacilli and macrophages. iv) In tuberculoid leprosy, the response is largely by CD4+ T cells, while in lepromatous leprosy although there is an excess of CD8+ T cells (suppressor T) but the macrophages and suppressor T cells fail to destroy the bacilli due to CD8+ T cell defect.

13. 4. Humoral response. Though the patients of lepromatous leprosy have humoral components like high levels of immunoglobulins (IgG, IgA, IgM) and antibodies to mycobacterial antigens but these antibodies do not have any protective role against lepra bacilli.

14. Tuberculoid Leprosy It is less severe form, which encompasses Tuberculoid (TT) Leprosy and borderline Tuberculoid (BT) Leprosy disease. In general, these forms of leprosy result in symptoms confined to the skin and peripheral nerves . The skin lesions of tuberculoid leprosy consist of one or a few hypopigmented macules or plaques that are sharply defined and hypesthetic, often have erythematous or raised borders, and are devoid of the normal skin organs (sweat glands and hair follicles) and thus are dry, scaly, and anhidrotic. AFB are generally absent or few in number. Tuberculoid leprosy patients may have asymmetric enlargement of one or a few peripheral nerves.

15. In tuberculoid le p r o s y , T cells br e a c h (p e r f or a te) the perineurium, and destruction of Schwann cells and axons may be evident, resulting in fibrosis of the epineurium, replacement of the endoneurium with epithelial granulomas, and occasionally caseous necrosis. Such invasion and destruction of nerves in the dermis by T cells are pathognomonic for leprosy.

16. Lepromatous Leprosy Lepromatous leprosy patients present with symmetrically distributed skin nodules, raised plaques, or diffuse dermal infiltration. Late manifestations include loss of eyebrows and eyelashes, pendulous earlobes, and dry scaling skin, particularly on the feet. In LL leprosy, bacilli are numerous in the skin, where they are often found in large clumps (globi), and in peripheral nerves, where they initially invade Schwann cells, resulting in foamy degenerative myelination and axonal degeneration and later in Wallerian degeneration. In addition, bacilli are plentiful in circulating blood and in all organ systems except the lungs and the central nervous system.

17. In lepromatous leprosy, nerve enlargement and damage tend to be symmetric, result from actual bacillary invasion, and are more insidious but ultimately more extensive than in tuberculoid leprosy. They may also have signs and symptoms related to involvement of the upper respiratory tract, the anterior chamber of the eye, and the testes. In untreated LL patients, lymphocytes regularly fail to recognize either M. leprae or its protein constituents, and lepromin skin tests are negative. Macrophages of lepromatous leprosy patients appear to be functionally intact; circulating monocytes exhibit normal microbicidal function and responsiveness to IFN-.

18. The important symptoms of leprosy are; Hypopigmented patches. Part i a l o r total loss o f cu t an e ous sensation i n the a f f ect e d area. Thickening of nerves. Presence of acid fast bacilli in skin or nasal smears. In advanced stages, leprosy can produce deformities like: Nodules in the skin, face and ears. Ulcers in the foot. Loss of fingers or toes. Nasal depression (mood disorder), foot drop and claw toes.

19. Specimens and Tests Depe n ding o n the f orm o f le p rosy sus pe c ted b y the tre a ting physician, the following specimens may be collected: Skin smears from the earlobes, elbows, and knees Skin biopsy from edges of active patches Nerve biopsy from thickened nerves Skin and nerve biopsy Biopsies are needed to definitively confirm a diagnosis of Hansen’s disease and to classify the disease, and slit skin smear may also be helpful in diagnosing those with mutlibacillary disease. Acid fast staining The Ziehl-Neelson method using 5% sulphuric acid is used. The presence of acid-fast bacilli confirms the diagnosis of Hansen’s disease.

20. Chemotherapy of leprosy: Sulph o n e s : d i a m i n o d i phe n yl Dapson s u lp h o n e (D D S) or Phenazine derivative : Clofazimine Anti tubercular drug : rifampicin, ethionamide Other drugs : ofloxacin, minocycline, clarithromycin

21. Detecti o n o f ca s es o f le p rosy and tracing th e contacts especially children of the patient’s house. P r evention of c o n t a c t be t w e en th e pati e nt and other normal, persons, especially children. Prevention treatment (chemoprophylaxis) with dapsone. Selecti v e iso l a tion o r hospi t al i z a tion o f th e patient showing acute reactions or complications. Rehabilit a ti o n of th e patients wi t h suitable wor k . Social and psychological rehabilitation is also necessary.