Mycobacterium lepra

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Mycobacterium lepra

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Mycobacterium Leprae: 

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

Leprosy: 

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

What is Leprosy?: 

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

LEPROSY: 

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 4

Transmission: 

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.

Carrier: 

Carrier Armadillo

What causes it?: 

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://genomenewsnetwork.org/articles/02_01/Leprosy.shtml http://www.worldproutassembly.org/leprosy%20patient%20holding%20flower.jpg Dr.T.V.Rao MD 7

Mycobacterium leprae: 

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 % H 2 So 4 Live bacilli, solid uniform structure. Dead appear as fragmented with granules. Dr.T.V.Rao MD 8

Mycobacterium leprae: 

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 9

Lepers are outcasts ?: 

Lepers are outcasts ? Dr.T.V.Rao MD 10

Bell to ring by Leper.: 

Bell to ring by Leper. Dr.T.V.Rao MD 11

Leprosy in India: 

Leprosy in India Dr.T.V.Rao MD 12

Bacterial Morphology: 

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 13

Cultivation: 

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

Important Experimental Animal: 

Important Experimental Animal Dr.T.V.Rao MD 15

Most Important experimental Animal: 

Most Important experimental Animal Dr.T.V.Rao MD 16

Resistance: 

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

Leprosy: 

Leprosy A chronic granulomatous disease Involves Skin, Peripheral nerves, Nasal mucosa, Affecting tissues and organs. Dr.T.V.Rao MD 18

Classification ( Madrid ): 

Classification ( Madrid ) Lepromatous Tuberculoid Dimorphic Intermediate. Refers to immune status Chemotherapy Host Immune Status Dr.T.V.Rao MD 19

Symptoms : 

Symptoms 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 There is two ways leprosy is presented:

Types of Leprosy: 

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

Ridley and Jopling Classification: 

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 22

WHO classification: 

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

WHO classification: 

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

Immunity: 

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

Immunity: 

Immunity HLA DR2 Tuberculoid HLA MTI HLA DQ Lepra reaction Dr.T.V.Rao MD 26

Pathology and Pathogenesis: 

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

Pathogenesis: 

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

Hyper reactive -Tuberculoid Leprosy: 

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

Anergic – Lepromatous leprosy: 

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

Other Intermediate Form: 

Other Intermediate Form Classified as 1 Borderline Tuberculoid 2 Mid borderline 3 Borderline lepromatous Dr.T.V.Rao MD 31

Who is at risk?: 

Who is at risk? Mainly affects: Skin Eyes The peripheral nerves Mucosa of the upper respiratory tract It can affect all ages and both sexes 95% of people who are exposed do not develop Dr.T.V.Rao MD 32

Who is at risk?: 

Who is at risk? http://microbes.historique.net/images/lep3.jpg http://www.leprosymission.org/web/pages/leprosy/images/girlwithleprosypatch.jpg http://www.leprosymission.org/web/pages/leprosy/leprosy.html bp2.blogger.com/.../s320/lepromatous_leprosy.jpg Dr.T.V.Rao MD 33

Other consequences: 

Other consequences Destruction of Nasal bones. Collapse of Nose Eye is damaged - lead to blindness. Dr.T.V.Rao MD 34

Pathology and Pathogenesis Tuberculoid Leprosy: 

Pathology and Pathogenesis Tuberculoid 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 35

Borderline Leprosy: 

Borderline Leprosy Contains characters of both Tuberculoid and Lepromatous leprosy Dr.T.V.Rao MD 36

PowerPoint Presentation: 

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

Diagnosis of Leprosy: 

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

Laboratory Diagnosis: 

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% H 2 So 4 Dr.T.V.Rao MD 39

PowerPoint Presentation: 

Dr.T.V.Rao MD 40

Z N Staining and description of bacilli: 

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

Smear Examination: 

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

The bacteriological index (BI) : 

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

Quantifying the bacillus as per WHO: 

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 44

Bacteriological Index: 

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

The Morphological index (MI): 

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

Morphological index (MI): 

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

Lepromin Test: 

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

Lepromin test: 

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 Farnedez reaction 2 Late Mitsuda reaction Dr.T.V.Rao MD 49

Lepromin Test: 

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

Lepromin Test (Cont): 

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

Problems of over diagnosis: 

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

Causes of under diagnosis: 

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

Treatment of Leprosy: 

Treatment of Leprosy Multidrug regime Rifampicin 600 mg / once month Dapsone 100/day Clofazimine 50 mg/daily. Continue for 6 months Other Drugs for Leprosy 1.Ethionamide 2.Prothionamide. Dr.T.V.Rao MD 54

About Dapsone: 

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

About Rifampicin: 

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

Pharmaceutical Treatment: 

Pharmaceutical Treatment M ultiple D rug T reatment (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

Side Effects: 

Side Effects Occasional cutaneous eruptions A slight reddish coloration of urine, sweat, and tears Brownish Black discoloration and dryness of skin Dapsone (DDS) Rifampicin (RFP) Clofazimine (CLF)

Dosage Cont’d......: 

Dosage Cont’d...... Multidrug Therapy for Paucibacillary (PB) Leprosy RFP Dapsone Adult 50-70kg 600mg/m* 100mg/d Child 10-14 years 450mg/m* 50mg/d Less than 10 years 300mg/m* 25mg/d PB patients treated with MDT are cured within six months *RFP monthly doses are given under supervision Dr.T.V.Rao MD 59

Cost of MDT- Funding: 

Cost of MDT- Funding Since 1995, WHO has supplied MDT 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 FREE

Prophylaxis: 

Prophylaxis Long term chemotherapy BCG vaccine useful Dr.T.V.Rao MD 61

Epidemiology: 

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

Prevention Of Leprosy: 

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

PowerPoint Presentation: 

Dr.T.V.Rao MD 64

What is Leprosy Today: 

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

PowerPoint Presentation: 

Dr.T.V.Rao MD 66

PowerPoint Presentation: 

Programmed Created by Dr.T.V.Rao MD for Medical and Paramedical Students in the Developing World Email doctortvrao@gmail.com Dr.T.V.Rao MD 67