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Mycobacterium Leprae

Mycobacterium Leprae. Dr.T.V.Rao MD. Leprosy. Vedas Bible Fear and Social outcasts Hansen 1868 - Identifies First microorganism Least understood and not cultured in artificial medium. What is Leprosy?. It is a disease of Historical importamce World's oldest recorded disease

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Mycobacterium Leprae

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  1. Mycobacterium Leprae Dr.T.V.Rao MD Dr.T.V.Rao MD

  2. Leprosy • Vedas • Bible • Fear and Social outcasts • Hansen 1868 - Identifies First microorganism • Least understood and not cultured in artificial medium Dr.T.V.Rao MD

  3. What is Leprosy? • It is a disease of Historical importamce • World's oldest recorded disease • Stigmatized disease • Gerhard Henrick Armauer Hansen Every year January 27 is World Leprosy Day Dr.T.V.Rao MD

  4. LEPROSY It is a chronic infectious disease caused by M.leprae, an acid fast, rod shaped bacillus. It mainly affects the skin, peripheral nerves, and mucosa of the respiratory tract etc., It has left behind a terrifying image in history and human memory of mutilation, rejection and exclusion from society. Dr.T.V.Rao MD

  5. Transmission • Scientist are not quite sure how the disease is trasmitted but they believe that: • It can be trassmitted from one person to another through the air.

  6. Carrier • Armadillo

  7. Tuberculoid Leprosy Symptoms  Severe pain Muscle weakness Skin stiffness and dryness Loss of fingers and toes Eye problems Blindeness Enlarged nerves Lepromatous Leprosy Symptom Thickened skin on face Nasal stuffiness Bloody nose Laryngitis Collapsing of the nose Swelling of the lymph nodes in the groin and armpits Scarring of the testes that leads to infertility Enlargement of male breasts Symptoms There is two ways leprosy is presented:

  8. What causes it? • Mycobacterium leprare • Rod Shaped • First bacterium disease in humans • Humans and Armadillos are only known natural hosts http://www.aaas.org/news/releases/2005/images/0512leprosy.jpg http://www.worldproutassembly.org/leprosy%20patient%20holding%20flower.jpg Dr.T.V.Rao MD http://genomenewsnetwork.org/articles/02_01/Leprosy.shtml

  9. Mycobacterium leprae • Appear as straight or curved rods • Size is 1 – 8 microns x 0.5 microns. • Polar bodies present as clubbed forms. • Lateral buds • Branching is observed. • Acid fast but less resistant only 5 % H2So4 • Live bacilli, solid uniform structure. • Dead appear as fragmented with granules. Dr.T.V.Rao MD

  10. Mycobacterium leprae • Acid fast bacilli • Strict human pathogens • Cannot be cultivated in-vitro • Armadillo’s used for obtaining M leprae • Transmission - ? Air borne • Low infectivity - prolonged contact required • Spectrum of clinical presentations • dependent on host –parasite interactions Tuberculoid Borderline Tuberculoid Borderline lepromatous Lepromatous Dr.T.V.Rao MD

  11. Lepers are outcasts ? Dr.T.V.Rao MD

  12. Bell to ring byLeper. Dr.T.V.Rao MD

  13. Leprosy in India Dr.T.V.Rao MD

  14. Bacterial Morphology • Bacilli may present in singles, can be intracellular. Agglomerates. • Bacilli bound by lipid like substance ( Glia) • Masses are Globi • Appear cigar bundles. Dr.T.V.Rao MD

  15. Cultivation • Not possible • Can be propagated in Foot pads of Mice • Granulomas develop at the site of inoculation. • Nine banded armadillo highly susceptible. • Chimpanzees • Generation time 12 -13 days. • Average may be 8- 42 days. Dr.T.V.Rao MD

  16. Important Experimental Animal Dr.T.V.Rao MD

  17. Most Important experimentalAnimal Dr.T.V.Rao MD

  18. Resistance • Viable for 9 -16 days, and in moist soil for 46 days • Direct sunlight for two hours. • Ultraviolet light for 30 minutes.. Dr.T.V.Rao MD

  19. Leprosy • A chronic glaucomatous disease • Involves Skin, Peripheral nerves, Nasal mucosa, Affecting tissues and organs. Dr.T.V.Rao MD

  20. Classification ( Madrid ) • Lepromatous • Tuberculoid • Dimorphic • Intermediate. Refers to immune status Chemotherapy Host Immune Status Dr.T.V.Rao MD

  21. Clinical spectrum of Leprosy LL BL BB BT TT IL Healthy contact MB Leprosy PB Leprosy Resistance to M. leprae

  22. Types of Leprosy • Depending on clinical features, leprosy is classified as: • Indeterminate Leprosy (IL) • Paucibacillary Leprosy (PB) • Borderline Tuberculoid Leprosy (BT) • Borderline borderline Leprosy (BB) • Borderline lepromatous Leprosy (BL) • Multibacillary Leprosy (MB) Dr.T.V.Rao MD

  23. Ridley and Jopling Classification • Divided in to 5 types 1 Tuberculoid 2 Borderline Tuberculoid. 3 Borderline. 4.Boderline lepromatous 5 lepromatous Dr.T.V.Rao MD

  24. WHO classification • Two Groups 1 Paucibacillary 2 Multibacillary , Paucibacillary (PB): the number of M. leprae in the body is small (less than 1 million) and a skin smear test is negative. The patient presents five or fewer skin lesions. Most cases of leprosy are PB. Dr.T.V.Rao MD

  25. WHO classification • 2 Multibacillary • M. leprae can multiple in the body almost without any check and is thus present in high numbers. The bacillus has likely spread to almost all areas of skin and peripheral nerves. A skin smear test is positive and the patient presents more than five skin lesions. Dr.T.V.Rao MD

  26. Immunity • Innate Immunity • Humeral x Cellular immune response. • CMI destroys the bacilli. • CMI determines the recovery. • Good CMI can manifest with Tuberculoid leprosy. • Good response with DH Tuberculoid leprosy. • Lepromatous leprosy patient have large number of CD 8 lymphocytes. Dr.T.V.Rao MD

  27. Immunity • HLA DR2 Tuberculoid • HLA MTI HLA DQ • Lepra reaction Dr.T.V.Rao MD

  28. Pathology and Pathogenesis • Bacilli seen as Globi inside lepra cells. • Can be seen extracellularly, • Multibacilllary disease. • Nodular lesions. • Granuloma. • Different pathways • Nodular lesions ulcerate • Invade mucosa of Nose, Mouth, URT • Involve RES, Eyes, Testis, Kidney. Bones Dr.T.V.Rao MD

  29. Pathogenesis • Leprosy target cell Schwanncell • Causes Anesthesia Muscle paralysis. • Repeated injuries to Anesthetic areas leads to gradual destruction. • Infiltration of skin, subcutaneous lesions leads to formation of visible lesions. • First lesions Non specific indeterminate skin lesions Dr.T.V.Rao MD

  30. Hyper reactive -TuberculoidLeprosy • Tuberculoid leprosy with small number of localized skin lesions, contain so few bacilli. • Glaucomatous response that often damages major nerve trunks. Dr.T.V.Rao MD

  31. Anergic – Lepromatous leprosy • Skin lesions are numerous or confluent • Contain high number of bacilli • Cluster of globi within monocytes Dr.T.V.Rao MD

  32. Other Intermediate Form • Classified as 1 Borderline Tuberculoid 2 Mid borderline 3 Borderline lepromatous Dr.T.V.Rao MD

  33. Who is at risk? • It can affect all ages and both sexes • Mainly affects: • Skin • Eyes • The peripheral nerves • Mucosa of the upper respiratory tract • 95% of people who are exposed do not develop Dr.T.V.Rao MD

  34. Who is at risk? bp2.blogger.com/.../s320/lepromatous_leprosy.jpg http://www.leprosymission.org/web/pages/leprosy/images/girlwithleprosypatch.jpg Dr.T.V.Rao MD http://microbes.historique.net/images/lep3.jpg http://www.leprosymission.org/web/pages/leprosy/leprosy.html

  35. Other consequences • Destruction of Nasal bones. • Collapse of Nose • Eye is damaged - lead to blindness. Dr.T.V.Rao MD

  36. Pathology and PathogenesisTuberculoid Leprosy , • Tuberculoid High degree of Immunity. Tuberculoid -- Few skin lesions, Sharply demarcated Maculo anesthetic patches • Neural Involvement. • Involves Hands and Feet. • Bacilli – few bacilli are seen • A paucibacillary diseases • CMI Adequate.Lepromin test positve • Good Prognosis Dr.T.V.Rao MD

  37. Contains characters of both Tuberculoid and Lepromatous leprosy Borderline Leprosy Dr.T.V.Rao MD

  38. How to diagnose leprosy • Examine skin • Check for patches • Test for sensation • Count the number of patches • Look for damage to nerves Dr.T.V.Rao MD

  39. Diagnosis of Leprosy • Diagnosis must therefore be made by doing a biopsy, in which a small piece of skin is taken to analyse for the leprosy bacterium. Early diagnosis is very important because it can prevent permanent deformities and disability. Dr.T.V.Rao MD

  40. Laboratory Diagnosis • Lepromatous – easy to diagnose. • Tuberculoid difficult • Histological examination 0n skin Biopsy • Detection for Acid Fast Bacilli. • Nasal discharges, • Slit skin smears. • Ear lobes • Take specimens from unaffected areas too • Stain with Z N method with 5% H2So4 Dr.T.V.Rao MD

  41. Dr.T.V.Rao MD

  42. Z N Staining and description of bacilli • Stain weakly, irregularly dead • Count the bacilli in high power field called as Bacterial index • Clinically active disease With No bacilli – Pauci bacillary disease • With bacilli - Multibacillary diseases Dr.T.V.Rao MD

  43. Smear Examination • 1 + 1 -10 bacilli / 100 fields • 2 + 1-10 bacilli / 10 fields. • 3 + 1 – 10 bacilli / one field. • 4 + 10 – 100 bacilli / one field • 5 + 100 - 1000 bacilli /field • 6 + > 1000 bacilli /field Number of Bacilli seen in each field is recorded as Bacillary index Dr.T.V.Rao MD

  44. The bacteriological index (BI) • This is an expression of the extent of bacterial loads. It is calculated by counting six to eight stained smears under the 100 x oil immersion lens. in a smear made by nicking the skin with a sharp scalpel and scraping it; Dr.T.V.Rao MD

  45. Quantifying the bacillus as per WHO • 1+ At least 1 bacillus in every 100 fields. • 2+ At least 1 bacillus in every 10 fields. • 3+ At least 1 bacillus in every field. • 4+ At least 10 bacilli in every field. • 5+ At least 100 bacilli in every field. • 6+ At least 1000 bacilli in every field. • Number of Bacilli seen in each field is recorded as Bacillary index Dr.T.V.Rao MD

  46. The Morphological index (MI) • This is calculated by counting the numbers of solid-staining acid-fast rods. Only the solid-staining bacilli are viable. It is not unusual for solid-staining M. leprae to reappear for short periods in patients being successfully treated with drugs. It is important to recognize that measurement of MI is liable for observer variations and therefore not always reliable. Dr.T.V.Rao MD

  47. Morphological index (MI) • The fluid and tissue obtained are spread fairly thickly on a slide and stained by the Ziehl-Neelsen method and decolorized (but not completely) which 1% acid alcohol. The results are expressed on a logarithmic scale. Dr.T.V.Rao MD

  48. Bacteriological Index • Indicates the Prognosis of the Disease • Total score in all smears ------------------------------------ Number of smears Eg 16/8 =2 So the index is 2 - Dr.T.V.Rao MD

  49. Lepromin test • Mitsuda in 1919. • Human source of bacilli Lepromin H • Armadillos source of bacilli Lepromin A • Bacillary Lepromin - Dharmendra antigen • Inject 0.1 ml of Lepromin Read for two types of reactions 1 Early Farnedz reaction 2 Late Mitsuda reaction Dr.T.V.Rao MD

  50. Lepromin Test • Mitsuda in 1919 – skin test – delayed hypersensitivity. • Lepromin is boiled emulsified lepromatous tissue –rich in lepra bacilli. • Lepromins, made from boiled bacilli from lepromatous lesions. • Leprosins ultisonicates of tissue free bacilli • Human source ,Leprosins –H ,Armadillo – Leprosins - A • Events in the reaction Biphasic reaction • Fernandez Reaction .> 24 – 48 hours, remains for 3 – 5 days, like tuberculin reaction, little significant. Dr.T.V.Rao MD

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