1 Leishmaniasis Leishmania donovani (complex) (VL) Leishmania tropica (CL) Leishmania major (CL)...

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Leishmaniasis Leishmaniasis

Leishmania donovani (complex)Leishmania donovani (complex) (VL) (VL)

Leishmania tropica (CL)Leishmania tropica (CL)

Leishmania major (CL)Leishmania major (CL)

Leishmania aethiopica (CL)Leishmania aethiopica (CL)

Leishmania mexicana (Complex) (CL)Leishmania mexicana (Complex) (CL)

Leishmania brazilliensis (complex) (MCL)Leishmania brazilliensis (complex) (MCL)

Leishmania perurianaLeishmania peruriana

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The ParasiteThe Parasite

• PhylumPhylum

• OrderOrder

• FamilyFamily

• GenusGenus

SarcomastigophoraSarcomastigophora

KinetoplastidaKinetoplastida

TrypanosomatidaeTrypanosomatidae

LeishmaniaLeishmania

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MorphologyMorphology

• PromasitogtePromasitogte• InsectInsect• MotileMotile• MidgutMidgut

• AmastigoteAmastigote• Mammalian stageMammalian stage• Non-motileNon-motile• IntracellularIntracellular

Digenetic Life CycleDigenetic Life Cycle

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MorphologyMorphology

• Promastigote • Amastigote

Flagella

Kinetoplast

Golgi

Nucleus

Cytoskeleton

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Promastigote

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• Amastigotes (*) of Leishmania donovani in the cells of a spleen.  The individual amastigotes measure approximately 1 µm in diameter. 

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Amastigote

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• Amastigotes of Leishmania in a macrophage from a lymph node of a dog. 

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• Leishmania (Leishman-Donovan or LD bodies). Lying in macrophage cells from liver. Giemsa. ×12000. Enlarged by 9.6.

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• A macrophage filled with Leishmania amastigotes.

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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 (Phlebotomus) species of blood-feeding sand flies (Phlebotomus) which carries the promastigote in the anterior gut and which carries the promastigote in the anterior gut and pharynx. It gains access to mononuclear phagocytes pharynx. It gains access to mononuclear phagocytes where it transform into amastogotes and divides until where it transform into amastogotes and divides until the infected cell ruptures. The released organisms the infected cell ruptures. The released organisms infect other cells. The sandfly acquires the organisms infect other cells. The sandfly acquires the organisms during the blood meal, the amastigotes transform into during the blood meal, the amastigotes transform into flagellate promastigotes and multiply in the gut until flagellate promastigotes and multiply in the gut until the anterior gut and pharynx are packed. Dogs and the anterior gut and pharynx are packed. Dogs and rodents are common reservoirs.rodents are common reservoirs.

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Mammalian HostsMammalian Hosts

• RodentsRodents• GerbilsGerbils• HyraxesHyraxes• BatsBats• PorcupinesPorcupines• OpossumsOpossums

• SlothsSloths• PrimatesPrimates• DogsDogs• FoxesFoxes• AnteatersAnteaters• . . . .. . . . .

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VectorsVectors

Phlebotomine SandfliesPhlebotomine Sandflies

6 genera world wide distribution6 genera world wide distribution

Phlebotomus & LutzomiaPhlebotomus & Lutzomia

500 species500 species

Females HaematophagusFemales Haematophagus

Males sap feedersMales sap feeders

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Clinical Disease

• Visceral• Fatal (90%

untreated)• Liver• Spleen• Bone marrow

• Cutaneous• Generally Self- healing • Skin• Mucous membranes

SPECTRUM OF DISEASE

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Initial Infection

• Similar in all species• Inoculation of promastigotes• Inflammation & chemotaxis• Receptor mediated phagocytosis

Promastigote Amasitgote Transformation

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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

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Visceral LeishmaniasisVisceral Leishmaniasis

• 19031903• 19201920• 19311931

William LeishmanWilliam Leishman

Pentavalent antimonyPentavalent antimony

Experimental transmissionExperimental transmission

Leishmania donovani (Complex)Leishmania donovani (Complex)

L.d. archibaldi - L.d.chagasi - L.d.donovani - Ld.infantumL.d. archibaldi - L.d.chagasi - L.d.donovani - Ld.infantum

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VL - Clinical ManifestationVL - Clinical Manifestation

Variable - Incubation 3-100+ weeksVariable - Incubation 3-100+ weeks

Lowgrade feverLowgrade fever

Hepato-splenomegalyHepato-splenomegaly

Bone marrow hyperplasiaBone marrow hyperplasia

Anemia, Leucopenia & CachexiaAnemia, Leucopenia & Cachexia

HypergammaglobulinnemiaHypergammaglobulinnemia

Epistaxis , Proteinuria, HematuriaEpistaxis , Proteinuria, Hematuria

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• Profile view of a teenage boy suffering from visceral leishmaniasis. The boy exhibits splenomegaly, distended abdomen and severe muscle wasting.

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• A 12-year-old boy suffering from visceral leishmaniasis. The boy exhibits splenomegaly and severe muscle wasting.

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• Jaundiced hands of a visceral leishmaniasis patient.

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• Enlarged spleen and liver in an autopsy of an infant dying of visceral leishmaniasis.

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Post Kala Azar Dermal Post Kala Azar 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

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Cutaneous leishmaniasis of the face. 

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A cutaneous leishmaniasis lesion on the arm.

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INFECTIONINFECTION

Sub-clinical or inapparent infectionSub-clinical or inapparent infection

Recovery DeathImmune to reinfection Concurrent infection

PKDL

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DiagnosisDiagnosis

Clinical signs & symptomsClinical signs & symptoms

HypergammaglobulinemiaHypergammaglobulinemiaELISA/Formol gelELISA/Formol gel

Bone marrow biopsyBone marrow biopsy

Spleen or liver biopsySpleen or liver biopsy

Culture & HistologyCulture & Histology

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SpeciationSpeciation

• Similar morphologySimilar morphology• Isoenzyme profiles - ZymodemesIsoenzyme profiles - Zymodemes• Monoclonal antibodiesMonoclonal antibodies• DNA hybridisation - PCRDNA hybridisation - PCR

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TreatmentTreatment

Good nursingGood nursing

DietDiet

AntibioticsAntibiotics

Pentavalent antimonyPentavalent antimony

PentamidinePentamidine

New drugs - New deliveryNew drugs - New delivery

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ControlControl

• Vector controlVector control• Reservoir controlReservoir control• Treatment of active casesTreatment of active cases• VaccinationVaccination