Mycobacterium leprae

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Mycobacterium leprae : 

Mycobacterium leprae

Morphology :Straight rods. 1 - 8 x 0.2 - 0.5µmSingle / groups. Intracellular.Acid fast bacilli with 5% H2 SO4.Bound together like cigar bundles by lipid- like substance: Glia. Globi present in virchow’s lepra cells or Foamy cells . : 

Morphology :Straight rods. 1 - 8 x 0.2 - 0.5µmSingle / groups. Intracellular.Acid fast bacilli with 5% H2 SO4.Bound together like cigar bundles by lipid- like substance: Glia. Globi present in virchow’s lepra cells or Foamy cells . Armauer Hansen in 1868

No artificial media / tissue culture available.Mouse : Intradermally into Foot pads. Granulomatous lesions in 1- 6 months.Intact CMI : Limited replication.↓CMI : Generalized leprosy.Armadillo: Highly susceptible. Chimpanzees, Manghabey monkey. : 

No artificial media / tissue culture available.Mouse : Intradermally into Foot pads. Granulomatous lesions in 1- 6 months.Intact CMI : Limited replication.↓CMI : Generalized leprosy.Armadillo: Highly susceptible. Chimpanzees, Manghabey monkey. Cultivation

Warm humid environment 9 - 16 days. 46 days in Moist soil 2 hours in Sunlight 30 minutes U V rays Surface lipid – Peptidoglycolipid (PGL-I ) A carbohydrate antigenic determinant. : 

Warm humid environment 9 - 16 days. 46 days in Moist soil 2 hours in Sunlight 30 minutes U V rays Surface lipid – Peptidoglycolipid (PGL-I ) A carbohydrate antigenic determinant. Resistance

World wide (tropics).Least infectious.Transmission -Nasal secretions. (Nasal blow releases 8 x 108 bacilli)Incubation period is 3-5 years.Continuous close contact.Rare in children < 5 Years.India : 12 million cases estimated -- 1980 2 millions -- 1996 : 

World wide (tropics).Least infectious.Transmission -Nasal secretions. (Nasal blow releases 8 x 108 bacilli)Incubation period is 3-5 years.Continuous close contact.Rare in children < 5 Years.India : 12 million cases estimated -- 1980 2 millions -- 1996 Epidemiology

I. Madrid (1953) 1. Lepromatous leprosy. 2. Tuberculoid leprosy. 3. Dimorphous leprosy. 4. Indeterminate leprosy. : 

I. Madrid (1953) 1. Lepromatous leprosy. 2. Tuberculoid leprosy. 3. Dimorphous leprosy. 4. Indeterminate leprosy. Classification of leprosy II. Ridley & Jopling1. Tuberculoid (T T).2. Borderline tuberculoid ( BT ).3. Borderline ( BB ).4. Borderline lepromatous (BL).5. Lepromatous leprosy ( LL ).

III. WHO classification Based on bacterial load. 1. Paucibacillary I, T T, BT 2. Multibacillary BB, BL, LL. : 

III. WHO classification Based on bacterial load. 1. Paucibacillary I, T T, BT 2. Multibacillary BB, BL, LL.

Slow, chronic & progressive Granulomatous disease of Peripheral nerves,skin and Muco- cutaneous tissues (Nasal mucosa). It affects Skin, Lungs, liver, testes ,bones. : 

Slow, chronic & progressive Granulomatous disease of Peripheral nerves,skin and Muco- cutaneous tissues (Nasal mucosa). It affects Skin, Lungs, liver, testes ,bones. Leprosy

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Source : Nasal or Skin discharges from lesion. Portal of entry: Damaged skin -Inoculation. Nasal mucosa- Inhalation Pathogenesis

Infiltration of bacilli in cooler body tissues like skin (nose, outer ear), testicles & superficial nerve endings→ (maculae) visible lesions. A non-specific or Indeterminate skin lesion is the First sign of disease. Schwann cell is target cell. Neuritis leads to Anesthesia & muscle paralysis. : 

Infiltration of bacilli in cooler body tissues like skin (nose, outer ear), testicles & superficial nerve endings→ (maculae) visible lesions. A non-specific or Indeterminate skin lesion is the First sign of disease. Schwann cell is target cell. Neuritis leads to Anesthesia & muscle paralysis. Pathogenesis contd….:

Tuberculoid leprosy Lesions are large maculae on skin, superficial nerve endings. CMI is intact. Low infectivity Lepromatous leprosy Extensive maculae, papules or nodules; Extensive destruction of skin. CMI severely depressed High infectivity Regression Progression

Generalized form with decreased CMI. “Lepromata” : Granulation tissue with plenty of vacuolated cells, from MN cells to Lepra cells. Ulceration Secondary infection & Mutilation of limbs. Skin lesions are extensive and bilaterally symmetrical. : 

Generalized form with decreased CMI. “Lepromata” : Granulation tissue with plenty of vacuolated cells, from MN cells to Lepra cells. Ulceration Secondary infection & Mutilation of limbs. Skin lesions are extensive and bilaterally symmetrical. Lepromatous leprosy

Face,ear lobules,hands and feet.Symmetrical thickening of peripheral nerves & anesthesia.Bacilli invade mucosa of Nose , Mouth and Respiratory tract → shed in secretions.Bacteremia present.Lepromin test is negative. CD8+ cells in plentyAuto antibodies are produced.Lateral part of eyebrows are lost. : 

Face,ear lobules,hands and feet.Symmetrical thickening of peripheral nerves & anesthesia.Bacilli invade mucosa of Nose , Mouth and Respiratory tract → shed in secretions.Bacteremia present.Lepromin test is negative. CD8+ cells in plentyAuto antibodies are produced.Lateral part of eyebrows are lost.

Lepromatous leprosy Lepromatous leprosy

Complications : Acute exacerbations. Testicular atrophy, Gynaecomastia Diffuse thickening of face – (Leonine face). Necrosis of nasal bones, cartilage with loss of upper incisors. Corneal ulcers. : 

Complications : Acute exacerbations. Testicular atrophy, Gynaecomastia Diffuse thickening of face – (Leonine face). Necrosis of nasal bones, cartilage with loss of upper incisors. Corneal ulcers.

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Borderline tuberculoid leprosy Borderline lepromatous Lesions are Slightly asymmetrical with or without anesthesia. Cirular, sharply demarcated lesions. Raised erythematous border with anesthesia.

Localized form in individuals with intact CMI.Skin lesions : Few hypo or hyper pigmented macular patches.Seen on Face, trunk and limbs.Bacilli are scanty or absent.Infectivity is low. : 

Localized form in individuals with intact CMI.Skin lesions : Few hypo or hyper pigmented macular patches.Seen on Face, trunk and limbs.Bacilli are scanty or absent.Infectivity is low. Tuberculoid leprosy

Diagnosed with Clinical + Histological evidences.Nerves : Peripheral Nerves to bigger nerves involved.Thickened, hard and tender.Lepromin test is positive.Auto antibodies production is rare. CD4+ cells. : 

Diagnosed with Clinical + Histological evidences.Nerves : Peripheral Nerves to bigger nerves involved.Thickened, hard and tender.Lepromin test is positive.Auto antibodies production is rare. CD4+ cells.

Peripheral neuropathy. V & VII th cranial nerve : Corneal ulcers. Ulnar nerve : Claw hand. Lateral popliteal nerve : Foot drop. Posterior tibial & medial nerve: Trophic ulcers, Loss of digits. : 

Peripheral neuropathy. V & VII th cranial nerve : Corneal ulcers. Ulnar nerve : Claw hand. Lateral popliteal nerve : Foot drop. Posterior tibial & medial nerve: Trophic ulcers, Loss of digits. Complications

Dimorphous type : Lesions resembles both LL (bacteriology) & T T (Clinically). May turn to complete LL or T T type.Indeterminate type: Early stages : Maculoanesthetic patches. Lesions are not like T T or LL Spontaneous healing. Turn to either LL or T T type. : 

Dimorphous type : Lesions resembles both LL (bacteriology) & T T (Clinically). May turn to complete LL or T T type.Indeterminate type: Early stages : Maculoanesthetic patches. Lesions are not like T T or LL Spontaneous healing. Turn to either LL or T T type.

Indeterminate type

Immunity : High degree of innate immunity. Induces both AMI & CMI. Antibodies are not effective. LL Pts : Large number of CD8 cells. TT Pts : Predominantly CD4 cells.Genetic relation: T T : HLA – DR2 L L : HLA MTI : 

Immunity : High degree of innate immunity. Induces both AMI & CMI. Antibodies are not effective. LL Pts : Large number of CD8 cells. TT Pts : Predominantly CD4 cells.Genetic relation: T T : HLA – DR2 L L : HLA MTI

Birth mark T. versicolor T.corporis Differential diagnosis of Leprosy

Lichen planus Vitiligo Pytiriasis alba

Fixed drug eruption Psoriasis Dermal leishmanoid Lupus vulgaris

Sarcoidosis Kaposi’s sarcoma

Lepra reactions: Acute inflammation of the disease due to Immunological reactions against bacilli. Medical emergency. Two types: Jopling type 1: CMI response against bacilli Synonym: Reversal reaction Occurrence: Spontaneous, Chemotherapy. Seen in BT, BB, BL. Due to influx of lymphocytes into lesions and changed to T T morphology. Lesions are painful, tender, Erythema and swelling. : 

Lepra reactions: Acute inflammation of the disease due to Immunological reactions against bacilli. Medical emergency. Two types: Jopling type 1: CMI response against bacilli Synonym: Reversal reaction Occurrence: Spontaneous, Chemotherapy. Seen in BT, BB, BL. Due to influx of lymphocytes into lesions and changed to T T morphology. Lesions are painful, tender, Erythema and swelling.

Jopling type 2 : ( Erythema nodosum leprosum ) Due to vasculitis (Antigen – Antibody complex). Seen in LL & BL few months after starting the chemotherapy. Characterised by: Tender, inflamed subcutaneous nodules. Fever. Lymphadenopathy, arthralgia.Lucio phenomenon: Cutaneous hemorrhagic infarct in LL cases. : 

Jopling type 2 : ( Erythema nodosum leprosum ) Due to vasculitis (Antigen – Antibody complex). Seen in LL & BL few months after starting the chemotherapy. Characterised by: Tender, inflamed subcutaneous nodules. Fever. Lymphadenopathy, arthralgia.Lucio phenomenon: Cutaneous hemorrhagic infarct in LL cases.

Main features of lepra reactions. Type 1 Type 2 1.Immunological basis : CMI Vasculitis with Ag – Ab deposits. 2. Type of patient : BT,BB, BL BL, LL. 3. Systemic disturbances : Not seen . Present. 4. Hematological disturbances: Not present Present 5. Proteinuria Not seen. Frequently present. 6.Relation to therapy Seen in first 6 months. Rare in first 6 months

Lepromin test : Skin test for delayed hypersensitivity to lepra bacilli. Antigens: 1. Boiled extract of Lepromatous tissue in isotonic saline. 2. Leprosins : Ultrasonicates of tissue – free bacilli from lesions. a). leprosins – H b). leprosins – A 3.Dharmender’s antigen. 4.Soluble antigen. : 

Lepromin test : Skin test for delayed hypersensitivity to lepra bacilli. Antigens: 1. Boiled extract of Lepromatous tissue in isotonic saline. 2. Leprosins : Ultrasonicates of tissue – free bacilli from lesions. a). leprosins – H b). leprosins – A 3.Dharmender’s antigen. 4.Soluble antigen.

Two types of reactions on Intradermal injection1. Early reaction of Fernandez : Erythema & Induration within 1 - 2 days Remains for 3 - 5 days. Poorly defined with little significance.2. Late reaction of Mistuda. Erythematous, indurated , granulomatous nodular skin lesion. Seen in 1 - 2 weeks reaches to peak in 4 weeks. Indicates CMI status in leprosy patients. : 

Two types of reactions on Intradermal injection1. Early reaction of Fernandez : Erythema & Induration within 1 - 2 days Remains for 3 - 5 days. Poorly defined with little significance.2. Late reaction of Mistuda. Erythematous, indurated , granulomatous nodular skin lesion. Seen in 1 - 2 weeks reaches to peak in 4 weeks. Indicates CMI status in leprosy patients.

Significance : 1. To classify the lesions of leprosy. T T ( + ) L L ( - ) Borderline (+/-)2. To assess prognosis & response to treatment. Positive: Good prognosis Negative: Bad prognosis3. To assess the resistance of individuals to leprosy. : 

Significance : 1. To classify the lesions of leprosy. T T ( + ) L L ( - ) Borderline (+/-)2. To assess prognosis & response to treatment. Positive: Good prognosis Negative: Bad prognosis3. To assess the resistance of individuals to leprosy.

Lab. Diagnosis Specimens : 1. Scrapings from Lesion ,Nasal mucosa. Z-N staining. Acid fast bacilli within the undifferentiated macrophages: L L Live bacilli : Solid, uniformly stained. Dead bacilli :Fragmented and granular. : 

Lab. Diagnosis Specimens : 1. Scrapings from Lesion ,Nasal mucosa. Z-N staining. Acid fast bacilli within the undifferentiated macrophages: L L Live bacilli : Solid, uniformly stained. Dead bacilli :Fragmented and granular.

Load of bacilli: 1. Bacteriological index: 1-10 / 100 oil immersion fields : 1+ 1 -10/10 “ “ : 2+ 1 -10 / 1 “ “ : 3+ 10-100/ field : 4+ 100-1000 /field : 5+ 2. Morphological index(% of uniformly stained bacilli) = Uniformly stained bacilli X 100 Total number of bacilli

2. Skin & Nerve biopsy. 3.Ear lobules ( Slit skin smear ). 5. Lepromin test : To know prognosis. Not for diagnosis. 6. Serological test : (a). MLPA (b). ELISA (Antibody against PGL-I). 7.Molecular diagnosis: Identifying DNA codes for 65 & 18-kDa M.leprae proteins.

Treatment : Until 1982 : Dapsone only. Now MDT being given because of resistant strains. WHO recommended Multi drug therapy Paucibacillary case. Rifampicin 600 mg/ month 6months Dapsone 100mg / day

Multi bacillary case: Rifampicin 600mg / month Dapsone 100 mg / day 2 or Clofazimine 300 mg / month more + years 50 mg / day Vaccines: BCG, MAI complex vaccine. Mycobacterium w vaccine. Chemoprophylaxis: MDT