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Mycobacterium lepra
Mycobacterium lepra
Mycobacterium lepra
Mycobacterium lepra
Mycobacterium lepra
Mycobacterium lepra
Mycobacterium lepra
Mycobacterium lepra
Mycobacterium lepra
Mycobacterium lepra
Mycobacterium lepra
Mycobacterium lepra
Mycobacterium lepra
Mycobacterium lepra
Mycobacterium lepra
Mycobacterium lepra
Mycobacterium lepra
Mycobacterium lepra
Mycobacterium lepra
Mycobacterium lepra
Mycobacterium lepra
Mycobacterium lepra
Mycobacterium lepra
Mycobacterium lepra
Mycobacterium lepra
Mycobacterium lepra
Mycobacterium lepra
Mycobacterium lepra
Mycobacterium lepra
Mycobacterium lepra
Mycobacterium lepra
Mycobacterium lepra
Mycobacterium lepra
Mycobacterium lepra
Mycobacterium lepra
Mycobacterium lepra
Mycobacterium lepra
Mycobacterium lepra
Mycobacterium lepra
Mycobacterium lepra
Mycobacterium lepra
Mycobacterium lepra
Mycobacterium lepra
Mycobacterium lepra
Mycobacterium lepra
Mycobacterium lepra
Mycobacterium lepra
Mycobacterium lepra
Mycobacterium lepra
Mycobacterium lepra
Mycobacterium lepra
Mycobacterium lepra
Mycobacterium lepra
Mycobacterium lepra
Mycobacterium lepra
Mycobacterium lepra
Mycobacterium lepra
Mycobacterium lepra
Mycobacterium lepra
Mycobacterium lepra
Mycobacterium lepra
Mycobacterium lepra
Mycobacterium lepra
Mycobacterium lepra
Mycobacterium lepra
Mycobacterium lepra
Mycobacterium lepra
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Mycobacterium lepra

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Mycobacterium lepra

Mycobacterium lepra

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  • 1. Mycobacterium Leprae Dr.T.V.Rao MD Dr.T.V.Rao MD 1
  • 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 2
  • 3. What is Leprosy?• It is a disease of Historical importamce• Worlds oldest recorded disease• Stigmatized disease• Gerhard Henrick Armauer Hansen Dr.T.V.Rao MD 3
  • 4. LEPROSYIt 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 therespiratory 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 4
  • 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. What causes it? •Mycobacterium leprare •Rod Shaped •First bacterium disease in humanshttp://www.aaas.org/news/releases/2005/images/0512 http://www.worldproutassembly.org/leprosyleprosy.jpg %20patient%20holding%20flower.jpg •Humans and Armadillos are only http://genomenewsnetwork.org/articles/02_01/Leprosy.shtml known natural hosts Dr.T.V.Rao MD 7
  • 8. 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 8
  • 9. 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 Borderline BorderlineTuberculoid Lepromatous Tuberculoid lepromatous Dr.T.V.Rao MD 9
  • 10. Lepers are outcasts ? Dr.T.V.Rao MD 10
  • 11. Bell to ring by Leper. Dr.T.V.Rao MD 11
  • 12. Leprosy in India Dr.T.V.Rao MD 12
  • 13. Bacterial Morphology•Bacilli may present in singles, can beintracellular. Agglomerates.•Bacilli bound by lipid like substance( Glia)•Masses are Globi•Appear cigar bundles. Dr.T.V.Rao MD 13
  • 14. 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 14
  • 15. Important Experimental Animal Dr.T.V.Rao MD 15
  • 16. Most Important experimental Animal Dr.T.V.Rao MD 16
  • 17. 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 17
  • 18. Leprosy• A chronic granulomatous disease• Involves Skin, Peripheral nerves, Nasal mucosa, Affecting tissues and organs. Dr.T.V.Rao MD 18
  • 19. Classification ( Madrid )1 Lepromatous2 Tuberculoid3 Dimorphic4 Intermediate. Refers to immune status Chemotherapy Host Immune Status Dr.T.V.Rao MD 19
  • 20. Symptoms There is two ways leprosy is presented: Lepromatous Leprosy SymptomTuberculoid Leprosy Symptoms • Thickened skin on face• Severe pain • Nasal stuffiness• Muscle weakness • Bloody nose• Skin stiffness and • Laryngitis dryness • Collapsing of the nose• Loss of fingers and toes • Swelling of the lymph nodes• Eye problems in the groin and armpits• Blindeness • Scarring of the testes that• Enlarged nerves leads to infertility • Enlargement of male breasts
  • 21. 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 21
  • 22. Ridley and Jopling Classification• Divided in to 5 types1 Tuberculoid2 Borderline Tuberculoid.3 Borderline.4.Boderline lepromatous5 lepromatous Dr.T.V.Rao MD 22
  • 23. 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 23
  • 24. 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 24
  • 25. Immunity• Innate Immunity• Humoral 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 25
  • 26. Immunity• HLA DR2 Tuberculoid• HLA MTI HLA DQ• Lepra reaction Dr.T.V.Rao MD 26
  • 27. 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 27
  • 28. 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 28
  • 29. Hyper reactive -Tuberculoid Leprosy• Tuberculoid leprosy with small number of localized skin lesions, contain so few bacilli.• Granulomatous response that often damages major nerve trunks. Dr.T.V.Rao MD 29
  • 30. Anergic – Lepromatous leprosy• Skin lesions are numerous or confluent• Contain high number of bacilli• Cluster of globi within monocytes Dr.T.V.Rao MD 30
  • 31. Other Intermediate Form• Classified as1 Borderline Tuberculoid2 Mid borderline3 Borderline lepromatous Dr.T.V.Rao MD 31
  • 32. Who is at risk?• It can affect all ages and both sexes• 95% of people who are exposed do not develop• Mainly affects: – Skin – Eyes – The peripheral nerves – Mucosa of the upper respiratory tract Dr.T.V.Rao MD 32
  • 33. Who is at risk? bp2.blogger.com/.../s320/lepromatous_lepr osy.jpg http://www.leprosymission.o rg/web/pages/leprosy/image s/girlwithleprosypatch.jpg Dr.T.V.Rao MD 33http://microbes.historique.net/images/lep3.jpg http://www.leprosymission.org/web/pages/lep rosy/leprosy.html
  • 34. Other consequences• Destruction of Nasal bones.• Collapse of Nose• Eye is damaged - lead to blindness. Dr.T.V.Rao MD 34
  • 35. Pathology and Pathogenesis Tuberculoid Leprosy,Tuberculoid High degree of Immunity.Tuberculoid -- Few skin lesions, Sharply demarcatedMaculo 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 35
  • 36. Borderline Leprosy• Contains characters of both Tuberculoid and Lepromatous leprosy Dr.T.V.Rao MD 36
  • 37. 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 37
  • 38. 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 38
  • 39. 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 39
  • 40. Dr.T.V.Rao MD 40
  • 41. 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 41
  • 42. 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 42
  • 43. 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 43
  • 44. 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 isrecorded as Bacillary index Dr.T.V.Rao MD 44
  • 45. 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 45
  • 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 46
  • 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 47
  • 48. 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 48
  • 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 LeprominRead for two types of reactions 1 Early Farnedez reaction 2 Late Mitsuda reaction Dr.T.V.Rao MD 49
  • 50. Lepromin Test• Mitsuda reaction occurs after 1 – 2 weeks. prominent after 4 weeks• Infiltration with Lymphocytes ,Epitheloid cells,and giant cells,• Indicates CMI• Differentiates those mount immune response and those cannot• Now antigens are derived from Armadillo derived lepra bacilli Dr.T.V.Rao MD 50
  • 51. Lepromin Test (Cont)• Test is not employed for Diagnosis of leprosy,• Effectiveness of CMI• Helps to asses the prognosis• Positive test good response /recovery• Negative Bad prognosis Dr.T.V.Rao MD 51
  • 52. Problems of over diagnosis • Wrong diagnosis in 0% to 28.6% (9.4%) Govt. of India, WHO, NIHFW 2004• Causes: 1. lack of knowledge by HCP to exclude dermatological and neurological conditions mimicking leprosy, therefore many doubtful cases included
  • 53. Causes of under diagnosis• Thicken peripheral nerve with sensory deficit highly subjective• Tools used for sensation testing in the field is of low to moderate scientific validity• Lesions on the face, difficult to elicit sensory impairment• Difficult to diagnose clinically the early LL cases without slit smear examination and or skin biopsy
  • 54. Treatment of Leprosy• Multidrug regime Rifampicin 600 mg / once month Dapsone 100/day Clofazimine 50 mg/daily. Continue for 6 monthsOther Drugs for Leprosy 1.Ethionamide 2.Prothionamide. Dr.T.V.Rao MD 54
  • 55. About Dapsone• It was discovered by German chemists Fromm and Wittmann in 1908• Was not utilized as a treatment until decades later• Available in 25mg & 100 mg tablets• Rated a pregnancy risk category C by the American Food and Drug Administration
  • 56. About Rifampicin• In the U.S. Rifampicin is marketed as: – Rifadin (Aventis) – Rifater ( in combination with isoniazid and pyrazinamide) (Aventis) – Rimactane (Novartis)• Do not wear contact lenses while taking Rifampicin• Rated a pregnancy risk category C by the American Food and Drug Administration
  • 57. Pharmaceutical Treatment• Multiple Drug Treatment (MDT) • There are several effective chemotherapeutic agents: Dapsone (diaphenylsulfone, DDS), Rifampicin (RFP), Clofazimine (CLF), Ofloxacin (OFLX), and Minocycline (MINO) constitute the backbone of the multidrug therapy (MDT) regimen. Dr.T.V.Rao MD 57
  • 58. Side Effects• Dapsone (DDS) • Occasional cutaneous eruptions• Rifampicin (RFP) • A slight reddish coloration of urine, sweat, and tears• Clofazimine (CLF) • Brownish Black discoloration and dryness of skin
  • 59. Dosage Cont’d......Multidrug Therapy for Paucibacillary (PB) Leprosy RFP Dapsone Adult 600mg/m* 100mg/d 50-70kg Child 450mg/m* 50mg/d 10-14 years Less than 10 300mg/m* 25mg/d years PB patients treated with MDT are cured within six months *RFP monthly doses are given under supervision Dr.T.V.Rao MD 59
  • 60. Cost of MDT- Funding• Since 1995, WHO has supplied MDT FREE FREE of cost to all leprosy patients in the world.• Initially drug funds were provided by Nippon Foundation• Since 2000, donations are provided by Novartis and the Novartis Foundation for Sustainable Development
  • 61. Prophylaxis• Long term chemotherapy• BCG vaccine useful Dr.T.V.Rao MD 61
  • 62. Epidemiology• Nasal secretions – rich source of infection,• Skin contact get infected.• Incubation 2 – 5 years.• May take 30 years to manifest.• I/3 world Leprosy patients are Indians.• Orissa and Bihar highest. Dr.T.V.Rao MD 62
  • 63. Prevention Of Leprosy• Early Diagnosis and treatment.• BCG vaccination ?• Health awareness and active surveillance high endemic areas• Field trails with different vaccines BCG + killed lepra bacilli ( ICRC ) bacillus have not given conclusive results. Dr.T.V.Rao MD 63
  • 64. Dr.T.V.Rao MD 64
  • 65. What is Leprosy Today• No at all a feared disease.• Only 5 % spouse infective rate• Leprosy is uncommon in most countries today, but it causes massive suffering in the areas where it is still found. These areas are largely confined to tropical and subtropical regions of Africa, Asia, and Central and South America.• . Dr.T.V.Rao MD 65
  • 66. Dr.T.V.Rao MD 66
  • 67. Programmed Created by Dr.T.V.Rao MDfor Medical and Paramedical Students in the Developing World Email doctortvrao@gmail.com Dr.T.V.Rao MD 67

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