1 / 38

Leprosy Hansen’s disease

Leprosy Hansen’s disease. Introduction . Leprosy is a chronic granulomatous infection of the skin and the peripheral nerves, with an intracellular bacterium Mycobacterium Lepra.

reginaldfrazier
Download Presentation

Leprosy Hansen’s disease

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Leprosy Hansen’s disease

  2. Introduction • Leprosy is a chronic granulomatous infection of the skin and the peripheral nerves, with an intracellular bacterium Mycobacterium Lepra. • Leprosy was recognized in the ancient civilization of China, Egypt, and India. The first known written mention of leprosy is dated 600BC.

  3. Introduction • Leprosy shows a wide range of clinical presentation from: • Tuberculoid leprosy (TT) • Borderline leprosy: borderline tuberculoid (BT), midborderline (BB), borderline lepromatous (BL). • Lepromatous leprosy (LL). (Classified by Ridley & Jopling 1966)

  4. A simpler field classifications depending on the number of skin lesions: • Single skin lesion (one patch). • Paucibacillary ( 2-5 patchs). • Multibacillary more than 5 patchs)

  5. Etiologic agent • Mycobacterium Leprae, discovered in 1873 by G.A. Hansen. • Intracellular parasite with tropism for macrophages and Schwann cells. • Viable bacilli stained with carbol-fuchsin appear as solid rods with rounded ends, while those is irregular stain are dead.

  6. Etiologic agent • M. leprae is an acid & alcohol fast (Ziehl-Neelsen), gram positive bacilli. • Prefer to grow in cooler regions of the body < 37ºc. • It has never been cultivated extracellularly, but organism can replicate in mouse footpad & 9-banded armadillo

  7. Etiologic agent • Genome include 1605 genes encoding proteins & 50 genes for stable RNA molecule. • More than half of the functional genes are replaced by inactive or pseudogenes, retaining the genes essential for Mycobacterial cell wall formation. • Thus M. leprae depend on host metabolic products, and this explain it’s slow rate of replication and inability to grow in culture. (Shin Y,et al. 2000)

  8. Etiologic agent • Mycobacterial cell wall contain several targets for host immune response: • Phenolic glycolipid I (PGL-I). • Lipoarabinomannan. • Other cell wall proteins purified from glycolipid component of cell wall.

  9. Phenolic glycolipid I (PGL-I). • Prominent surface lipid specific for M. leprae. • Best characterized virulent factor: • Binds to C3,»»» phagocytosis of the bacterium by mononuclear phagocytes. • Protect against oxidative killing by hydroxyl radicals and superoxide anions.

  10. Phenolic glycolipid I (PGL-I). • Specific tropism for Schwann cells: • Trisaccharide terminal of PGL-I »»» G domain of α 2 chain of laminin 2, a basal component of lamina of Schwann cells restricted to peripheral nerves. • Stimulates host immune response: • Potent IgM antibody response, that is proportional to bacterial load and fall with therapy. (Sridharan, et al. 2005)

  11. Lipoarabinomannan: • Modulates macrophages phagocytic activity, & proteins involved in cell wall synthesis. • Other cell wall proteins purified from glycolipid component of cell wall: • Act as potent T-cell antigens, stimulate protective immunity in murine M. leprae infection. (Britton & Lockwood, 2004)

  12. Epidemiology Prevalence: • In the past 20 years more than 14 million patients have been cured. • In 1985 »»» 12/10 000, dropped in 2000 »» > 1/10 000, with a 20% annual decrease in new cases detected globally since 2001. • Leprosy is eliminated from 113 countries of 122 where leprosy was considered a public health problem in 1985.

  13. Epidemiology • In 9 countries in Africa, Asia & Latin America »»» more than 1/10 000 • Eighty three % of cases are present in 6 countries: India, Brazil, Burma, Indonesia, Madagascar & Nepal. • India account for 64% of cases world wide. (WHO, 2005)

  14. WHO African region leprosy elimination program meeting in 2003

  15. Epidemiology • Primary host is human. Naturally occurring infection is also reported armadillos in America & African chimpanzee. • Sex: Male more affected than females (M/F ratio 1.5-2 to 1) except in some areas of Africa. • Age: All ages, about 20% of cases occur in children below 10 years, but it is extremely rare in infants.

  16. Transmission • Aerosol spread of nasal secretion, & uptake through nasal or respiratory mucosa. • M. Leprae in nasal secretion can survive up to 36 hours, or as much as nine days in tropical areas. • Proximity is an important determinant of transmission, & incidence among houses hold contacts: 8-10 for lepromatous leprosy. 2-4 for tuberculoid leprosy (Sridharan, et al. 2005)

  17. Incubation Period • Varies widely from months to 30 years • With a mean of 4 years for TT and 10 years for LL. • Subclinical infection is reported in areas of high prevalence, as M. leprae DNA was detected in 5% of nasal swabs from normal individuals. (Britton & Lockwood, 2004)

  18. Host susceptibility • Genetic factors can affect both the development and the pattern of the disease: • susceptibility loci on chromosomes 10 & 6 »» Indian patients. • Polymorphism TNF- promoter genes »» multibacillary leprosy in Brazilian patients. • HLA DR2 & DR3 »» »» tuberculoid diseases, while HLA DQ1with lepromatous form • Mutation in toll-like receptor-2 gene »» »» lepromatous leprosy in Koreans. (Britton & Lockwood, 2004)

  19. Pathogenesis • Clinical forms of the diseases depend on the ability to mount a cell mediated immune response. • One pole (TT) »»vigorous CMI »» lesions infiltrated with Th1-like Tcell» » IFN  , TNF α, IL-2 and IL-15 »»well demarcated granulomas with few mycobacteria found in the lesions. • Diseases is limited to few well defined skin patchs or nerve trunks.

  20. Other pole (LL): • Absent specific cellular immunity,»» uncontrolled proliferation of bacilli with many lesions and extensive infiltration of the skin and nerves. • There is no organized granuloma, foamy macrophages, and high antibody titer to PGL-I. • Deviation of CD4+ve T cells, with Th2 like cytokines IL-4 and IL-10, deletion of T cells, or suppressor T cells

  21. Pathogenesis • Most of the patients have the intermediate form (BT,BB, and BL). • They are unstable and either progress: • Slowly toward lepromatous pole, or • Type 1 leprosy reaction (reversal reaction) Spontaneous increased T cell reactivity & in cytokines IFN  , TNF α • Type 2 reaction (erythema nodosum leprosum) Systemic inflammatory immune response»» extravascular immune complexes »» neutrophil infiltration, complement activation and high concentration of TNF α

  22. Clinical features • Skin involvement: Commonly macules or plaques rarely papules or nodules are seen. In tuberculoid and BT, lesions are few, hypopigmented with raised edges, and with reduced sensation

  23. Clinical features • Lepromatous form, many skin lesion, symmetrical, confluent in some cases, and many of them are not hypoaesthetic.

  24. Clinical features

  25. Clinical features • Nerve damage: • Peripheral nerve trunk damage: Posterior tibial, ulnar, median, lateral popliteal and facial. Involved nerves are enlarged, and with regional sensory and motor loss. • Small dermal sensory & autonomic nerves: Hypoaesthesia »» TT and BT. Glove & stocking »» lepromatous form. • Pure neuritic leprosy:

  26. Clinical features • Eye involvement: • Blindness »»» nerve damage & direct invasion • Lagophthalmus »»» orbicularis oculi »»» zygomatic & temporal branches of facial nerve. • Corneal ulceration »»» anaesthesia »»» ophthalmic branch of trigeminal nerve.

  27. Clinical features • Systemic features: • Nasal mucosa »»» cartilage »»» saddle shape. • Bone destruction »»» osteomylitis. • Testicular atrophy »»» loss of testosterone . • Renal involvement and amyloidosis

  28. Diagnosis • Lepromin test: • Intradermal inoculation of killed M leprae. • Early reactions (48 h, Fernandez) • Late reactions (3-4 wk, Mitsuda) • strongly positive responses (>5 mm) in TT or BT, while patients with LL do not respond.

  29. Diagnosis • Slit smear technique: • Skin incision in 6 sites ( ear lobes, elbow, knee and a lesion) • Slit is smeared on a slide and stained with Ziehl-Neelsen. • Microscopic score (1+ to 6+), reflect number of bacilli by HPF • Useful to quantitate bacterial load • High specificity but low sensitivity 70%

  30. 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. • Polymarase 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.

  31. Diagnosis • Histologic diagnosis: • In TT: Noncaseating 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

  32. Treatment • Chemotherapy: All patient should receive multi-drug therapy (MDT). First line drugs: Rifampicin, Clofazimine, and Dapsone.

  33. Treatment Second line therapy: Minocycline, clarithromycin, and ofloxacin, are highly effective against M. leprae. Reversal reaction: Peak time: during the first 2 month of therapy, even up 12 months, and after (MDT) is completed. Corticosteroids 40-60mg daily, taper 5 mg every 2-4 weeks, duration of therapy 3-4 months. Recovery rate for nerve function 60-70%, less with pre-existing nerve damage or recurrent reaction.

  34. Treatment Type 2 reaction (ENL): Develop during 1st or 2nd year of MDT, and can relapse over several years. Anti- inflammatory: Clofazimine 300mg daily. Or Drug that target overproduction of TNF-α,Thalidomide 400mg daily, or pentoxifylline. Or Neutralization of TNF-α with monoclonal antibodies, or soluble inhibitors.

  35. Prophylaxis • Immunoprophylaxis: • BCG offer variable protection against leprosy (34-80%) in different countries, adding heat –killed M. leprae increases the protective effect to 64%. • Endemicity of leprosy, background saprophytic mycobacterial flora, and the age at vaccine may affect the response to vaccination. • Vaccination may precipitate TT leprosy in apparently healthy contacts, thus immunoprophylaxis is best carried out at an early age. • Chemoprophylaxis: • Rifampicin, to close contact of a case, and can be give to children under the age 12 years (15mg/kg monthly for 6 months)

  36. Pregnancy & leprosy • Little evidence that pregnancy can cause new diseases or relapse. • However, pregnant BL patients may experience type 1 reaction in the post partum period. • Also lepromatous leprosy patients can experience ENL during pregnancy and lactation, with early loss of nerve function than non-pregnant patients. • MDT (Rifampicin, Clofazimine, and Dapsone) is safe.

  37. HIV infection & leprosy • Unlike tuberculosis, leprosy is not significantly associated with HIV infection. • HIV-associated neuropathy might be confused with leprosy neuritis, also neuropathy due to antiretroviral chemotherapy might be confused with leprosy. • There is difference in treatment strategy for patients with leprosy and HIV, icluding treatment of reactions.

  38. Thank you

More Related