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Ntm m leprae leprosy

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  • 1. Non-Tuberculous Mycobacteria (NTM) Mycobacterium leprae Dr Kamran Afzal Asst Prof Microbiology
  • 2. NTM (Non-Tuberculous Mycobacteria)
    • Atypical mycobacteria
    • MOTT
    • Importance of NTM
      • Ability to cause disease in the immunocompromised host
      • Potential as laboratory contaminants
      • Effect on the immune response e.g. sensitization with these mycobacteria may cause a false positive tuberculin skin reaction
  • 3. Characteristics of NTM/ Differences from MTB
    • Wider temperature range for growth
    • Growth rates tend to be more variable
    • Many are pigmented yellow to orange
    • Generally resistant to first line anti-tuberculosis drugs
    • Human infections are frequently associated with pre-existing disease or trauma
    • NTM generally produce smooth colonies
    • Lack of transmission of NTM from patient to patient
  • 4. Reservoir of Mycobacteria Soil, water, animals Yes M chelonae Soil, water, animals Yes M fortuitum Unknown No M ulcerans Soil, water, birds Possibly M avium- intracellulare Soil, water Possibly M scrofulaceum Fish, water Rarely M marinum Water, cattle Rarely M kansasii Human No M leprae Human, cattle No M bovis Human No M tuberculosis Reservoir Environmental contaminant Mycobacterium
  • 5. Groups of NTM
    • Group I (Photo-Chromogens)
    • M. kansasii , M. marinum
    • Group II (Scoto-Chromogens)
    • M. scrofulaceum, M. suzulgii
    • Group III (Non-Chromogens)
    • M. avium, M. intracellulare
    • Group IV (Rapidly Growing)
    • M. fortuitum, M. chelonei
  • 6. Pathogenicity of NTM
    • Infection of cervical lymph nodes
    • Presents as cervical lymphadenopathy- Scrofula
    • Treatment – surgery
    M. kansasii
    • Respiratory infection in compromised hosts
    • Present like pulmonary tuberculosis
    • Treatment – susceptible to anti TB drugs
    M. scrofulaceum
  • 7. Pathogenicity of NTM M. avium-intracellulare
    • Infection of cervical lymph nodes
    • Presents as cervical lymphadenopathy
    • Treatment – Clarithromycin+ethambutol,
    • Rifabutin or ciprofloxacin
    • Severe RTI
    • Severe GI infection
    • Septicaemia
    Immuno-competent host Immuno-deficient host AIDS
  • 8. M. ulcerans
    • ‘ Buruli’ ulcer
    • Prolonged incubation required for growth
    M. fortuitum / M. chelonei
    • Injection related abscesses
    • Associated with sternal wound infections
    • Treatment: Amikacin + Doxycycline
    • Chronic infection of the skin called swimming pool granuloma
    • Treated with minocycline
    M. marinum
  • 9. ‘ Buruli’ ulcer
  • 10. Epidemiology
  • 11.  
  • 12. Global Leprosy Case-load : 1985 Vs 2000 Vs 2003 The dramatic decline is attributed to the effective use of multi-drug therapy(MDT) 0.6 Million 2000 0.5 Million < 1 Million 12 Million 2003 1998 1985 NIL- Multi-Drug Resistance following MDT is NOT reported 11.2 million 100% 1/10,000 14 2000 NIL - Multi-Drug Resistance following MDT is NOT reported High-since single drug-dapsone was given for long periods, in low doses 5. Drug Resistance 13.5 million Accurate Data Not Available 4. Patients Cured 100% < 10% 3. Patients on MDT < 1/10,000 10/10,000 2. Global Prevalence 9 122 1. Number of Countries with Prevalence Rates of > 1/10,000 population 2003 1985 Parameter
  • 13. Global Leprosy Situation In January 2004 Prevalence as of 1 January 2004
  • 14. Mycobacterium leprae
    • Discovered in 1873 by G.A. Hansen
    • Aerobic, non-motile, non-sporing, straight or slightly curved rods, acid fast (Modified ZN stain)
    • M. leprae is not very infectious; long term contact with infected individuals is required for transmission
  • 15.
    • Obligatory intra-cellular organism
    • Non-cultivable in-vitro
    • It grows in mouse foot pads and in armadillos, not on laboratory media
    • Slow growing with doubling time of 14 days
    • Optimal temp for growth is 30 o C, so it grows in the skin and peripheral nerves
    • Tropism for macrophages and Schwann cells
  • 16. Leprosy
    • Leprosy is a chronic granulomatous infection of the skin and the peripheral nerves, due to an intracellular bacterium Mycobacterium leprae, that may result in disability and deformity
    • Leprosy was recognized in the ancient civilization of China, Egypt, and India
      • The first known written mention of leprosy is dated 600 BC
  • 17. Epidemiology
    • 83% of the world’s registered cases are in 6 countries
      • India, Nepal, Tanzania, Brazil, Madagascar, Mozambique
    • 700,000 new cases are detected annually
    • In the world, recorded cases 18 million
    • Slowly decline in European countries due to
      • Strict isolation
      • Socio-economic development
    • No association between HIV and leprosy
  • 18.
    • Human to human
    • By contact
      • Individuals in close, repeated, skin to skin and prolonged association or proximity with leprosy patients
    • Respiratory route
      • The respiratory route is gaining increasing attention
      • The inability of the organisms to be found on the surface of the skin
      • The demonstration of a large number of morphologically intact organisms in the nasal discharge
      • Entry also through nasal mucosa
      • Patients with LL are more infectious than TB
    • Insects
      • Lepra bacilli demonstrated in biting insects, actual transmission?
    Modes of transmission
  • 19. Virulence factors
    • Mycobacterial cell wall contain several factors
      • Phenolic glycolipid I (PGL-I)
      • Lipoarabinomannan (LAM)
      • Other cell wall proteins purified from glycolipid component of cell wall
  • 20. Leprosy Classifications
    • Ridley-Jopling
    • TT - BT - BB - BL - LL
      • – Skin lesions
      • – Bacterial load
      • – Histology
    • WHO Classification
      • – Paucibacillary (2-5 skin lesions)
      • – Multibacillary (>6 lesions)
      • Operational
  • 21. Leprosy Types Ridley-Jopling Classification Nil Many with globi Many with globi LL Poor Few Moderate BL Partial None Few BB Less good None None or few BT Good None None TT Immune response Bacilli in nasal smears Bacilli in skin smears Leprosy type
  • 22. Pathogenesis
    • IP varies widely from months to 30 years
    • Long incubation times
      • – 2-5 years TT
      • – 8-10 years LL
    • Brief bacteremic phase
    • Binds to skin macrophages and Schwann cells
    • Elicits immune response - development of host protective immunity or progression to established leprosy
  • 23. Pathogenesis
    • Vigorous CMI »» well demarcated granulomas with few mycobacteria found in the lesions
    Absent specific cellular immunity »» uncontrolled proliferation of bacilli with many lesions and extensive infiltration of the skin and nerves
  • 24. Lepromatous and Tuberculoid Leprosy Tuberculoid leprosy Low infectivity Localised infection Normal serum Ig Normal T cell response Poor growth of mycobacteria in macrophages (Pauci-bacillary) Positive Lepromin test Lepromatous leprosy High infectivity Disseminated infection Hyper-gammaglobulinaemia Non-responsive Florid growth of mycobacteria in macrophages (Multi-bacillary) Negative Lepromin test
  • 25. Tuberculoid Leprosy
    • Single or few well defined lesions
    • Flattened area with raised edges
    • No sensation or perspiration
    • Hypo-pigmented
    • No lepra bacilli in lesions
  • 26. Mech of Sensory Loss
    • Mycobacterium leprae , activates ErbB2 receptors on the surface of myelinating Schwann cells
    • The subsequent activation of Erk1/2 by phosphorylation results in demyelination
  • 27. Borderline Leprosy
    • Skin lesions few in BT to several in BL
    • BT lesions moderate to marked loss of sensation and perspiration
    • No bacteria in BT and BB while a few in BL
  • 28. Lepromatous Leprosy
    • Wide-spread
    • Small and many lesions
    • Shiny, no loss of sensation
    • May be nodular
    • Large number of bacteria present
  • 29. Clinical Picture
  • 30. Clinical Picture
  • 31. Clinical Diagnosis - Leprosy
    • How to assess the patient?
    • Examine skin
    • Check for patches
    • Test for sensation
    • Count the number of patches
    • Look for damage to nerves
  • 32. Signs of Leprosy
    • Pale or slightly reddish patch
    • Loss of sensation in the patch
    • Signs of damage to nerves
      • loss of sensation
      • weakness of muscles of hands/feet/face
      • visible deformity of hands/feet/face
  • 33. Effects of sensory loss Sensory fibre loss Decreased sensation Patient may not feel • HEAT • PAIN • TOUCH • PRESSURE Because of NO PAIN, Patient neglects injuries Decreased sensation
  • 34. Effects of sensori-motor loss
  • 35. The eye in leprosy
    • Blinding complications
    • lagophthalmos
    • decreased corneal sensation
    • acute iritis
    • chronic iritis
    • cataract
  • 36. Lab Diagnosis
    • Lepromin Test
    • Intradermal inoculation of killed M. leprae
      • Examine site of inoculation every 48 hours for 21 days
    • Early reactions (48 h, Fernandez)
    • Late reactions (3-4 wk, Mitsuda)
      • Nodule about 5 mm
    • Strongly positive responses (>5 mm) in TT or BT, while patients with LL do not respond
  • 37. Lab Diagnosis
    • Skin Slit Smear Technique
    • Skin incision in 6 sites (ear lobes, elbows, knees)
    • Slit is smeared on a slide and stained with Ziehl-Neelsen
    • Microscopic score (1+ to 6+), reflect number of bacilli/field
    • Useful to quantitate bacterial load
    • High specificity but low sensitivity 70%
  • 38. ZN staining
  • 39. Bacterial Index
    • 0: no bacilli observed
    • 1+: 1-10 in 10-100 fields
    • 2+: 1-10 in 1-10 fields
    • 3+: 1-10 in 1 field
    • 4+: 10-100 1 field
    • 5+: 100-1000 field
    • 6+: many clumps
    • (over 1000 bacilli) per field
  • 40. Lab Diagnosis
    • Serology
    • ELISA: to detect antibodies against carbohydrate portion of the PGL-I
    • Postive in lepromatous but not the tuberculoid form
    • Antibody titer decreases with effective therapy
    • Polymerase Chain Reaction (PCR)
    • Amplify the DNA of M. leprae
    • Low bacterial loads (<10 bacilli) can be detected
    • 60-75% of smear -ve patients with TT leprosy have positive results on PCR
  • 41. Lab Diagnosis
    • Histologic diagnosis
    • In TT : Non-caseating granuloma, bacilli are few or absent, dermal nerve involvement, with normal skin organs
    • In LL : Diffuse granulomatous reaction, foamy macrophages, more common around blood vessels and nerves
  • 42. Treatment
    • Treat the infection
    • Treat reactions and nerve damage
    • Prevent neuropathic damage
    • Education
    • Psychological support
    • Reduce stigma
  • 43. Treatment Regimens
    • Rifampicin/Clofazimine/Dapsone
      • – MB cases
      • – 12 months
    • Rifampicin/dapsone
      • – PB
      • – 6 months
    • Second line therapy
      • Minocycline, clarithromycin, and ofloxacin, are also highly effective against M. leprae
  • 44. Treatment
  • 45. Prevention
    • No vaccine
    • Isolation of the infected cases
    • Avoid over crowding
    • Education of masses
    • Dapsone or rifampicin prophylaxis to the exposed individuals especially children