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1 Leishmaniasis Leishmaniasis Leishmania donovani Leishmania donovani (complex)(complex) (VL) (VL) Leishmania tropica Leishmania tropica (CL)(CL) LeishmaniaLeishmania major (CL) major (CL) Leishmania aethiopicaLeishmania aethiopica (CL) (CL) Leishmania mexicanaLeishmania mexicana (Complex) (CL) (Complex) (CL) Leishmania brazilliensisLeishmania brazilliensis (complex) (complex) (MCL)(MCL) Leishmania perurianaLeishmania peruriana 2 The ParasiteThe Parasite PhylumPhylum OrderOrder FamilyFamily GenusGenus SarcomastigophoraSarcomastigophora KinetoplastidaKinetoplastida TrypanosomatidaeTrypanosomatidae LeishmaniaLeishmania 3 MorphologyMorphology PromasitogtePromasitogte InsectInsect MotileMotile MidgutMidgut AmastigoteAmastigote Mammalian stageMammalian stage Non-motileNon-motile IntracellularIntracellular Digenetic Life CycleDigenetic Life Cycle 4 MorphologyMorphology PromastigoteAmastigote Flagella Kinetoplast Golgi Nucleus Cytoskeleton 5 Promastigote 6 Amastigotes (*) of Leishmania donovani in the cells of a spleen. The individual amastigotes measure approximately 1 m in diameter. 7 Amastigote 8 Amastigotes of Leishmania in a macrophage from a lymph node of a dog. 9 Leishmania (Leishman- Donovan or LD bodies). Lying in macrophage cells from liver. Giemsa. 12000. Enlarged by 9.6. 10 A macrophage filled with Leishmania amastigotes. 11 Life cycleLife cycle The organism is transmitted by the bite of several The organism is transmitted by the bite of several species of blood-feeding sand flies (species of blood-feeding sand flies (PhlebotomusPhlebotomus) ) which carries the which carries the promastigotepromastigote in the anterior gut in the anterior gut and pharynx. It gains access to mononuclear and pharynx. It gains access to mononuclear phagocytes where it transform into phagocytes where it transform into amastogotesamastogotes and divides until the infected cell ruptures. The and divides until the infected cell ruptures. The released organisms infect other cells. The sandfly released organisms infect other cells. The sandfly acquires the organisms during the blood meal, the acquires the organisms during the blood meal, the amastigotesamastigotes transform into flagellate transform into flagellate promastigotespromastigotes and multiply in the gut until the anterior gut and and multiply in the gut until the anterior gut and pharynx are packed. Dogs and rodents are common pharynx are packed. Dogs and rodents are common reservoirs.reservoirs. 12 13 Mammalian HostsMammalian Hosts RodentsRodents GerbilsGerbils HyraxesHyraxes BatsBats PorcupinesPorcupines OpossumsOpossums SlothsSloths PrimatesPrimates DogsDogs FoxesFoxes AnteatersAnteaters . . . . . . . 14 VectorsVectors Phlebotomine SandfliesPhlebotomine Sandflies 6 genera world wide distribution6 genera world wide distribution PhlebotomusPhlebotomus & & LutzomiaLutzomia 500 species500 species Females Females HaematophagusHaematophagus Males sap feedersMales sap feeders 15 16 Clinical Disease Visceral Fatal (90% untreated) Liver Spleen Bone marrow Cutaneous Generally Self- healing Skin Mucous membranes SPECTRUM OF DISEASE 17 Initial Infection Similar in all species Inoculation of promastigotes Inflammation & chemotaxis Receptor mediated phagocytosis Promastigote Amasitgote Transformation 18 Parasite SpreadParasite Spread Macrophage Macrophage lysis lysis & parasite release& parasite release Lymphatic spreadLymphatic spread Blood spreadBlood spread Target organsTarget organs Skin/lymph nodes/spleen/liver/Skin/lymph nodes/spleen/liver/ bone marrowbone marrow 19 Visceral LeishmaniasisVisceral Leishmaniasis 19031903 19201920 19311931 William William LeishmanLeishman PentavalentPentavalent antimony antimony Experimental transmissionExperimental transmission LeishmaniaLeishmania donovani donovani (Complex)(Complex) L.d. L.d. archibaldiarchibaldi - L.d. - L.d.chagasichagasi - L.d. - L.d.donovanidonovani - Ld. - Ld.infantuminfantum 20 VL - Clinical ManifestationVL - Clinical Manifestation Variable - Incubation 3-100+ weeksVariable - Incubation 3-100+ weeks LowgradeLowgrade fever fever HepatoHepato- -splenomegalysplenomegaly Bone marrow Bone marrow hyperplasiahyperplasia AnemiaAnemia, , LeucopeniaLeucopenia & & CachexiaCachexia HypergammaglobulinnemiaHypergammaglobulinnemia EpistaxisEpistaxis , , ProteinuriaProteinuria, , HematuriaHematuria 21 Profile view of a teenage boy suffering from visceral leishmaniasis. The boy exhibits splenomegaly, distended abdomen and severe muscle wasting. 22 A 12-year-old boy suffering from visceral leishmaniasis. The boy exhibits splenomegaly and severe muscle wasting. 23 Jaundiced hands of a visceral leishmaniasis patient. 24 Enlarged spleen and liver in an autopsy of an infant dying of visceral leishmaniasis. 25 Post Post Kala AzarKala Azar Dermal Dermal LeishmanoidLeishmanoid Normally develops 2 years after Normally develops 2 years after recoveryrecovery RecrudescenceRecrudescence Restricted to skinRestricted to skin Rare but varies geographicallyRare but varies geographically 26 Cutaneous leishmaniasis of the face. 27 A cutaneous leishmaniasis lesion on the arm. 28 INFECTIONINFECTION Sub-clinical or Sub-clinical or inapparentinapparent infection infection Recovery Death Immune to reinfection Concurrent infection PKDL 29 DiagnosisDiagnosis Clinical signs & symptomsClinical signs & symptoms HypergammaglobulinemiaHypergammaglobulinemia ELISA/ELISA/FormolFormol gel gel Bone marrow biopsyBone marrow biopsy Spleen or liver biopsySpleen or