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Leishmaniasis for 3rd

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Leishmaniasis for 3rd year.

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Leishmaniasis for 3rd

  1. 1. LEISHMANIASIS : Dr.Mohamad Shaikhani.
  2. 2. LEISHMANIASIS : <ul><li>Caused by unicellular flagellate intracellular protozoa. </li></ul><ul><li>3 clinical syndromes: </li></ul><ul><li>Visceral leishmaniasis (VL, kala-azar) </li></ul><ul><li>Cutaneous leishmaniasis (CL) </li></ul><ul><li>Mucosal leishmaniasis (ML). </li></ul><ul><li>Most caused by zoonotic transmission from animals (chiefly canine /rodent reservoirs) to humans through phlebotomine sandfly. </li></ul><ul><li>Humans are the only known reservoir (anthroponotic) in major VL foci in India /Sudan. </li></ul><ul><li>The disease occurs in 88 countries, with annual incidence of 2 million new cases (500 000 for VL,1.5 million for CL). </li></ul>
  3. 3. 3- Another sandfly bites human and ingests blood infected with Leishmania 2- Sandfly bites human and injects Leishmania into skin 1- Sandfly bites animal and ingests blood infected with Leishmania 4- Cycle continues when sandfly bites another human or animal reservoir
  5. 5. VISCERAL LEISHMANIASIS (KALA-AZAR): <ul><li>Caused by protozoon Leishmania donovani complex, transmitted by the phlebotomine sandfly. </li></ul><ul><li>Rarely, a dermatotropic species (e.g. Leishmania tropica ) may cause visceral disease. </li></ul><ul><li>India, Sudan, Bangladesh,Brazil account for 90% of cases of VL, ,others include the Mediterranean, East Africa, China, Arabia, Israel & other South American countries. </li></ul><ul><li>Transmission reported to follow blood transfusion in N Europe. </li></ul><ul><li>Can present unexpectedly in immunosuppressed as renal transplantation & AIDS </li></ul>
  8. 8. Pathogenesis: <ul><li>The great majority remain asymptomatic&control the infection. </li></ul><ul><li>Those unable to do so develop clinical disease. </li></ul><ul><li>In visceral diseases the spleen, liver, bone marrow & lymph nodes are primarily involved. </li></ul>
  9. 9. Clinical features: <ul><li>In India both adults/ children equally affected; in others predominantly children / infants, except if HIV co-infection. </li></ul><ul><li>Malnutrition increases susceptibility to the visceral disease. </li></ul><ul><li>The IP: weeks-months (occasionally several years). </li></ul>
  10. 10. Clinical features: <ul><li>The first sign is high fever, usually accompanied by rigor /chills. </li></ul><ul><li>Fever intensity decreases over time & patients may become afebrile for intervening periods ranging from weeks to months, followed by a relapse of fever, often of lesser intensity. </li></ul><ul><li>Splenomegaly develops quickly in the first few weeks & becomes massive as the disease progresses, hepatomegaly occurs later, to a lesser degree than splenomegaly. </li></ul><ul><li>Lymphadenopathy is seen in the majority in Africa,Mediterranean &South America but is rare in India. </li></ul>
  11. 11. Clinical features: <ul><li>Black skin or kala-azar (Hindi word), is a feature of advanced illness, now rarely seen. </li></ul><ul><li>Pancytopenia with its clinical manifestations is a common feature. </li></ul><ul><li>Moderate to severe anemia develops rapidly& result in CHF &associated clinical features. </li></ul><ul><li>Thrombocytopenia, often with hepatic dysfunction, may result in bleeding from retina, GIT& nose. </li></ul>
  12. 12. Clinical features: <ul><li>In progressive disease, hypoalbuminaemia causes leg oedema , ascites & anasarca & if advanced, profound immunosuppression &secondary infections are very common,as TB, pneumonia, amoebic or bacillary dysentery, gastroenteritis, herpes zoster& chickenpox. </li></ul><ul><li>Skin infections, boils, cellulitis & scabies are common occurrences. </li></ul><ul><li>Without adequate treatment most die. </li></ul>
  13. 13. Investigations: <ul><li>Pancytopenia is the most dominant feature, with granulocytopenia &monocytosis. </li></ul><ul><li>Polyclonal hypergammaglobulinaemia, chiefly IgG followed by IgM& hypoalbuminaemia are seen later. </li></ul><ul><li>Patients are anergic to the leishmanin antigen skin test (LST)& there is antigen-specific immunosuppression when peripheral blood mononuclear cells are challenged with Leishmania antigen ex vivo. </li></ul><ul><li>After successful chemotherapy there is recovery of immunity & the LST becomes positive. </li></ul>
  14. 14. Diagnosis: <ul><li>Demonstration of amastigotes (Leishman-Donovan bodies) in splenic smears is the most efficient means of diagnosis, with 98% sensitivity; but carries a risk of serious haemorrhage. </li></ul><ul><li>Safer methods like BM or LN smears are not as sensitive. </li></ul><ul><li>Parasites may be demonstrated in buffy coat smears, especially in immunosuppressed patients. </li></ul><ul><li>Sensitivity can be improved by culturing the aspirate material,but expensive& only available in well-equipped labs. </li></ul><ul><li>PCR for DNA detection from the peripheral blood is an efficient non-invasive method for diagnosis, but is only in specialised labs& also used for species identification. </li></ul>
  15. 15. Diagnosis: <ul><li>Serodiagnosis, by ELISA or immunofluorescence antibody test, is employed in developed countries. </li></ul><ul><li>In endemic regions, a highly sensitive/specific direct agglutination test of stained promastigotes & an equally efficient rapid immunochromatographic k39 strip test have become popular. </li></ul><ul><li>These tests remain positive for several months after cure, so do not predict response to treatment or relapse. </li></ul><ul><li>A significant proportion of the healthy population in an endemic region will be positive for these tests due to past exposure. </li></ul>
  16. 16. Diagnosis:
  17. 19. Differential diagnosis: <ul><li>Malaria </li></ul><ul><li>Typhoid </li></ul><ul><li>Tuberculosis </li></ul><ul><li>Schistosomiasis </li></ul><ul><li>Many other infectious &neoplastic conditions, some of which may coexist with VL. </li></ul><ul><li>Fever, splenomegaly, pancytopenia & non-response to antimalarial therapy may provide the clue before specific lab diagnosis is made. </li></ul>
  18. 20. Treatment: Pentavalent antimonials <ul><li>Antimony (Sb) compounds were the first drugs used & remain the mainstay. </li></ul><ul><li>The exception is the India, where almost two-thirds of cases are refractory. </li></ul><ul><li>Traditionally, pentavalent antimony is available as sodium stibogluconate (100 mg/ml) & meglumine antimoniate (85 mg/ml). </li></ul><ul><li>The daily dose is 20 mg/kg body weight, given either intravenously or intramuscularly for 28-30 days. </li></ul><ul><li>Side-effects are common and include arthralgias, myalgias, raised hepatic transaminases, pancreatitis, especially in patients co-infected with HIV&ECG changes (T wave inversion and reduced amplitude). </li></ul><ul><li>Severe cardiotoxicity, manifested by concave ST segment elevation, prolongation of QTc > 0.5 msec, ventricular ectopics, runs of ventricular tachycardia, torsades de pointes, ventricular fibrillation & sudden death, is not uncommon. </li></ul><ul><li>The incidence of cardiotoxicity & death can be very high with improperly manufactured Sb </li></ul>
  19. 21. Amphotericin B <ul><li>Given once daily or on alternate days for 15-20 doses, is used in patients with Sb failure or unresponsiveness. </li></ul><ul><li>It has a cure rate of nearly 100%. </li></ul><ul><li>Infusion-related side-effects, e.g. high fever with rigor, thrombophlebitis, diarrhoea & vomiting, are extremely common. </li></ul><ul><li>Serious adverse events, as renal or hepatic toxicity, hypokalaemia, thrombocytopenia, myocarditis& occasional death, are not uncommon. </li></ul><ul><li>Lipid formulations & liposomal amphotericin B are less toxic. </li></ul>
  20. 22. Miltefosine <ul><li>An alkyl phospholipid, approved for the treatment of VL. </li></ul><ul><li>A daily dose of 50 mg (patient's body weight < 25 kg) to 100 mg (≥ 25 kg), or 2.5 mg/kg body weight for children, for 28 days cures over 90%. </li></ul><ul><li>Side-effects include mild to moderate vomiting /diarrhoea/ rarely skin allergy or nephrotoxicity. </li></ul><ul><li>Since it is a teratogenic drug, it cannot be used in pregnancy; female patients are advised not to become pregnant for the duration of treatment &another 2 months, because of its half-life of nearly 1 week. </li></ul>
  21. 23. Paromomycin <ul><li>An aminoglycoside, highly effective if given intramuscularly at 15 mg/kg body weight daily for 3 weeks. </li></ul><ul><li>No significant auditory or renal toxicity is seen. </li></ul>
  22. 24. Post-kala-azar dermal leishmaniasis <ul><li>(PKDL) After treatment &recovery from the visceral disease in India & Sudan some patients develop dermatological manifestations. </li></ul><ul><li>In India dermatological changes occur in a small minority of patients 6 months to ≥ 3 years after the initial infection seen as macules, papules, nodules (most frequently) & plaques which have a predilection for the face, especially the area around the chin. </li></ul><ul><li>The face often appears erythematous. </li></ul><ul><li>Hypopigmented macules can occur over all parts of the body &are highly variable in extent and location. </li></ul><ul><li>There are no systemic symptoms & no spontaneous healing. </li></ul>
  23. 25. Post-kala-azar dermal leishmaniasis <ul><li>The diagnosis is clinical, supported by demonstration of scanty parasites in lesions by slit skin smear&culture. </li></ul><ul><li>Immunofluorescence & immunohistochemistry are other methods for demonstration of the parasite in skin tissues. </li></ul><ul><li>In the majority of patients serological tests (direct agglutination test or k39 strip tests) are positive. </li></ul><ul><li>Treatment of PKDL is difficult. Sb for 120 days or several courses of amphotericin B infusions are required. </li></ul><ul><li>In the absence of a physical handicap, most patients are reluctant to complete the treatment. </li></ul><ul><li>PKDL patients are a human reservoir& focal outbreaks have been linked to patients with PKDL in areas previously free of VL. </li></ul>
  24. 26. kala-azar prevention: <ul><li>Multipronged approach is needed. </li></ul><ul><li>Sandflies are extremely sensitive to insecticides & vector control through insecticide spray is very important. </li></ul><ul><li>Mosquito nets or curtains treated with insecticides will keep out the tiny sandflies. </li></ul><ul><li>In endemic areas with zoonotic transmission, infected or stray dogs should be destroyed. </li></ul><ul><li>In areas with anthroponotic transmission, early diagnosis & treatment of human infections, to reduce the reservoir & control epidemics of VL, is extremely important. </li></ul><ul><li>Serology is useful for screening of suspected cases in the field. </li></ul><ul><li>No vaccine is currently available . </li></ul>
  25. 27. Cutaneous & mucous leishmaniasis: Solitary facial lesions with satellites Hyraxes L. aethiopica Rapid necrosis, wet sores Gerbils, desert rodents L. major Oriental sore(Baghdad boil) Dogs L. tropica Clinical features Host Leishmania species
  26. 28. Post-kala-azar dermal leishmaniasis
  27. 29. Cutaneous leishmaniasis.