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Leishmaniasis

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Leishmaniasis

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Leishmaniasis

  1. 1. Leishmaniasis Dr. Sachin Adukia Dept. of Internal Medicine
  2. 2. Leishmaniasis: Introduction Definition • Encompassing a complex group of disorders, leishmaniasis is caused by unicellular eukaryotic obligatory intracellular protozoa of the genus Leishmania and primarily affects the host's reticuloendothelial system. • Leishmania species produce widely varying clinical syndromes ranging from self-healing cutaneous ulcers to fatal visceral disease. • These syndromes fall into three broad categories: visceral leishmaniasis (VL), cutaneous leishmaniasis (CL), and mucosal leishmaniasis (ML).
  3. 3. LeishmaniasisLeishmaniasis Leishmania donovani (complex) (VL)* Leishmania tropica (CL)** Leishmania major (CL) Leishmania aethiopica (CL) Leishmania mexicana (Complex) (CL) Leishmania brazilliensis (complex) (MCL)*** Leishmania peruriana * VL – visceral leishm. **CL – cutaneous leishm. ***MCL - muco-cut. Leishm.
  4. 4. Epidemiology Visceral Leishmaniasis • VL (also known as kala-azar, a Hindi term meaning "black fever") is caused by the L. donovani complex, which includes L. donovani and L. infantum (the latter designated L. chagasi in the New World); these species are responsible for anthroponotic and zoonotic transmission, respectively. India and neighboring Nepal, Bangladesh, Sudan, and Brazil are the four largest foci of VL and account for 90% of the world's VL burden, with India the worst affected
  5. 5. The ParasiteThe Parasite • PhylumPhylum • OrderOrder • FamilyFamily • GenusGenus SarcomastigophoraSarcomastigophora KinetoplastidaKinetoplastida TrypanosomatidaeTrypanosomatidae LeishmaniaLeishmania
  6. 6. MorphologyMorphology • PromasitogtePromasitogte • InsectInsect • MotileMotile • MidgutMidgut • AmastigoteAmastigote • Mammalian stageMammalian stage • Non-motileNon-motile • IntracellularIntracellular Digenetic Life CycleDigenetic Life Cycle
  7. 7. MorphologyMorphology • Promastigote • Amastigote Flagella Kinetoplast Golgi Nucleus Cytoskeleton
  8. 8. Promastigote
  9. 9. • Amastigotes (*) of Leishmania donovani in the cells of a spleen.  The individual amastigotes measure approximately 1 µm in diameter. 
  10. 10. 1 Amastigote
  11. 11. 1 • Amastigotes of Leishmania in a macrophage from a lymph node of a dog. 
  12. 12. 1 • Leishmania (Leishman- Donovan or LD bodies). Lying in macrophage cells from liver. Giemsa. ×12000. Enlarged by 9.6.
  13. 13. 1 • A macrophage filled with Leishmania amastigotes.
  14. 14. 1 Life cycleLife cycle • The organism is transmitted by the bite of severalThe organism is transmitted by the bite of several species of blood-feeding sand flies (Phlebotomus)species of blood-feeding sand flies (Phlebotomus) which carries the promastigote in the anterior gutwhich carries the promastigote in the anterior gut and pharynx. It gains access to mononuclearand pharynx. It gains access to mononuclear phagocytes where it transform into amastogotesphagocytes where it transform into amastogotes and divides until the infected cell ruptures. Theand divides until the infected cell ruptures. The released organisms infect other cells. The sandflyreleased organisms infect other cells. The sandfly acquires the organisms during the blood meal, theacquires the organisms during the blood meal, the amastigotes transform into flagellate promastigotesamastigotes transform into flagellate promastigotes and multiply in the gut until the anterior gut andand multiply in the gut until the anterior gut and pharynx are packed. Dogs and rodents are commonpharynx are packed. Dogs and rodents are common reservoirs.reservoirs.
  15. 15. 1
  16. 16. 1 Mammalian HostsMammalian Hosts • RodentsRodents • GerbilsGerbils • HyraxesHyraxes • BatsBats • PorcupinesPorcupines • OpossumsOpossums • SlothsSloths • PrimatesPrimates • DogsDogs • FoxesFoxes • AnteatersAnteaters • othersothers
  17. 17. 1 VectorsVectors Phlebotomine SandfliesPhlebotomine Sandflies 6 genera with world wide distribution6 genera with world wide distribution Genus :Phlebotomus & LutzomiaGenus :Phlebotomus & Lutzomia 500 species500 species
  18. 18. 1
  19. 19. 1 Clinical Disease • Visceral • Fatal (90% untreated) • Liver • Spleen • Bone marrow • Cutaneous • Generally Self- healing • Skin • Mucous membranes
  20. 20. 2 Initial Infection • Similar in all species • Inoculation of promastigotes • Inflammation & chemotaxis • Receptor mediated phagocytosis Promastigote Amasitgote Transformation
  21. 21. 2 Parasite SpreadParasite Spread Macrophage lysis & parasite releaseMacrophage lysis & parasite release Lymphatic spreadLymphatic spread Blood spreadBlood spread Target organsTarget organs Skin/lymph nodes/spleen/liver/Skin/lymph nodes/spleen/liver/ bone marrowbone marrow
  22. 22. 2 Visceral Leishmaniasis Immunopathogenesis • The majority of individuals infected by L. donovani or L. infantum mount a successful immune response and control the infection, never developing symptomatic disease. Forty-eight hours after intradermal injection of killed promastigotes, these individuals exhibit delayed-type hypersensitivity to leishmanial antigens in the leishmanin skin test (also called the Montenegro skin test). Acquired resistance to leishmanial infection is controlled by the production of interleukin (IL) 12 ,interferon (IFN) , tumor necrosis factor (TNF) , and other proinflammatory cytokines by the T helper 1 (TH1) T lymphocytes. Organs of the reticuloendothelial system are predominantly affected, with remarkable enlargement of the spleen, the liver, and lymph nodes. The tonsils and intestinal submucosa are also heavily infiltrated with parasites. Bone marrow dysfunction results in pancytopenia.
  23. 23. 2 VL - Clinical ManifestationVL - Clinical Manifestation Variable - Incubation 3-100+ weeksVariable - Incubation 3-100+ weeks Lowgrade fever with chills and rigorsLowgrade fever with chills and rigors Splenomegaly (by 2Splenomegaly (by 2ndnd wk) followed by Hepatomegalywk) followed by Hepatomegaly LN enlargement is rare in IndiaLN enlargement is rare in India Wt. Loss and Cachexia with hyperpigmentation common in brownWt. Loss and Cachexia with hyperpigmentation common in brown individualsindividuals Pedal edema with ascites(due to hypoalbuminemia)Pedal edema with ascites(due to hypoalbuminemia) Bone marrow hyperplasia wih eventual marrow dysfunctionBone marrow hyperplasia wih eventual marrow dysfunction Anaemia – severe enough to cause CCFAnaemia – severe enough to cause CCF Leucopenia -Leucopenia - Secondary infections such as measles, pneumonia, tuberculosis, bacillary or amebic dysentery, and gastroenteritis are common. Alonwtih Herpes zoster, chickenpox, boils in the skin, and scabies .. Thrombocytopenia- Epistaxis , Proteinuria, HematuriaThrombocytopenia- Epistaxis , Proteinuria, Hematuria Untreated, the disease is fatal in most patients, including 100% of those with HIV co-infection.
  24. 24. 2 • Profile view of a teenage boy suffering from visceral leishmaniasis. The boy exhibits splenomegaly, distended abdomen and severe muscle wasting. 
  25. 25. 2 • A 12-year-old boy suffering from visceral leishmaniasis. The boy exhibits splenomegaly and severe muscle wasting.
  26. 26. 2 • Jaundiced hands of a visceral leishmaniasis patient. 
  27. 27. 2 • Enlarged spleen and liver in an autopsy of an infant dying of visceral leishmaniasis.
  28. 28. 2 Post Kala Azar DermalPost Kala Azar Dermal Leishmanoid (PKDL)Leishmanoid (PKDL) Normally develops <2 years afterNormally develops <2 years after recoveryrecovery RecrudescenceRecrudescence Restricted to skinRestricted to skin Rare but varies geographicallyRare but varies geographically
  29. 29. 2 Post–kala-azar dermal leishmaniasis in an Indian patient.
  30. 30. 3 • In PKDL, parasites are scanty in hypopigmented macules but may be seen and cultured more easily from nodular lesions. Cellular infiltrates are heavier in nodules than in macules. Lymphocytes are the dominant cells; next most common are histiocytes and plasma cells. In about half of cases, epithelioid cells—scattered individually or forming compact granulomas—are seen. The diagnosis is based on history and clinical findings, but rK39 and other serologic tests are positive in most cases.
  31. 31. 3 Cutaneous leishmaniasis of the face. 
  32. 32. 3 A cutaneous leishmaniasis lesion on the arm.
  33. 33. 3 Diagnosis of VLDiagnosis of VL Clinical signs & symptomsClinical signs & symptoms HypergammaglobulinemiaHypergammaglobulinemia ELISA/Formol gelELISA/Formol gel Bone marrow biopsyBone marrow biopsy Spleen or liver biopsySpleen or liver biopsy Culture & HistologyCulture & Histology
  34. 34. 3 TreatmentTreatment Good nursingGood nursing DietDiet Antibiotics*Antibiotics* Pentavalent antimony compunds*Pentavalent antimony compunds* New drugsNew drugs * With emphasis on current recommended pharmacotherapy only* With emphasis on current recommended pharmacotherapy only
  35. 35. 3 Pharmacotherapy of VL A pentavalent antimonial is the drug of choice in most endemic regions of the world, but there is widespread resistance to antimony in the Indian state of Bihar, where either amphotericin B (AmB) deoxycholate , parmomycin or miltefosine is preferred• Two pentavalent antimonial (SbV ) preparations are available: sodium stibogluconate (100 mg of SbV /mL) • meglumine antimonate (85 mg of SbV /mL). • The daily dose is 20 mg/kg by rapid IV infusion or IM injection, and therapy continues for 28–30 days. • Cure rates exceed 90% in Africa, the Americas, and most of the Old World but are <50% in Bihar, India, as a result of resistance. • Adverse reactions to SbV treatment are common and include arthralgia, myalgia, and elevated serum levels of aminotransferases. • Electrocardiographic changes such as prolongation of QTc to >0.5 s may herald ventricular arrhythmia and sudden death.
  36. 36. 3 Amphotericin B • Conventional AmB deoxycholate is administered in doses of 0.75–1.0 mg/kg on alternate days for a total of 15 infusions. • Fever with chills is an almost universal adverse reaction to AmB infusions. Nausea and vomiting are also common, as is thrombophlebitis in the infused veins. • Acute toxicities can be minimized by administration of antihistamines like chlorpheniramine and antipyretic agents like acetaminophen before each infusion. • AmB can cause renal dysfunction and hypokalemia and in rare instances elicits hypersensitivity reactions, bone marrow suppression, and myocarditis, all of which can be fatal.
  37. 37. 3 • Paromomycin is approved in India for the treatment of VL at an IM dose of 11 mg of base/kg daily for 21 days; this regimen produces a cure rate of 95% • Miltefosine recommended therapeutic regimens for patients on the Indian subcontinent are a daily dose of 50 mg for 28 days for patients weighing <25 kg, a twice-daily dose of 50 mg for 28 days for patients weighing 25 kg, and 2.5 mg/kg for 28 days for children 2–11 years of age. These regimens result in a cure rate of 94% in India.
  38. 38. 3 ControlControl • Vector controlVector control • Reservoir controlReservoir control • Treatment of active casesTreatment of active cases • VaccinationVaccination
  39. 39. 3 Thank you…!

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