Leishmaniasis Leishmania donovani complex VL Leishmania tropica CL

Leishmaniasis Leishmania donovani (complex) (VL) Leishmania tropica (CL) Leishmania major (CL) Leishmania aethiopica (CL) Leishmania mexicana (Complex) (CL) Leishmania brazilliensis (complex) (MCL) Leishmania peruriana 1

The Parasite • Phylum Sarcomastigophora • Order Kinetoplastida • Family Trypanosomatidae • Genus Leishmania 2

Morphology Digenetic Life Cycle • Promasitogte • Insect • Motile • Midgut • Amastigote • Mammalian stage • Non-motile • Intracellular 3

Morphology • Promastigote • Amastigote Flagella Kinetoplast Golgi Nucleus Cytoskeleton 4

Promastigote 5

• Amastigotes (*) of Leishmania donovani in the cells of a spleen. The individual amastigotes measure approximately 1 µm in diameter. 6

Amastigote 7

• Amastigotes of Leishmania in a macrophage from a lymph node of a dog. 8

• Leishmania (Leishman. Donovan or LD bodies). Lying in macrophage cells from liver. Giemsa. × 12000. Enlarged by 9. 6. 9

• A macrophage filled with Leishmania amastigotes. 10

Life cycle • The organism is transmitted by the bite of several species of blood-feeding sand flies (Phlebotomus) which carries the promastigote in the anterior gut and pharynx. It gains access to mononuclear phagocytes where it transform into amastogotes and divides until the infected cell ruptures. The released organisms infect other cells. The sandfly acquires the organisms during the blood meal, the amastigotes transform into flagellate promastigotes and multiply in the gut until the anterior gut and pharynx are packed. 11

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Mammalian Hosts • • • Rodents Gerbils Hyraxes Bats Porcupines Opossums • • • Sloths Primates Dogs Foxes Anteaters. . . 13

Vectors Phlebotomine Sandflies 6 genera world wide distribution Phlebotomus & Lutzomia 500 species Females Haematophagus Males sap feeders 14

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Clinical Disease • Visceral • Fatal (90% untreated) • Liver • Spleen • Bone marrow • Cutaneous • Generally Self- healing • Skin • Mucous membranes SPECTRUM OF DISEASE 16

Initial Infection • • Similar in all species Inoculation of promastigotes Inflammation & chemotaxis Receptor mediated phagocytosis Promastigote Amasitgote Transformation 17

Parasite Spread Macrophage lysis & parasite release Lymphatic spread Blood spread Target organs Skin/lymph nodes/spleen/liver/ bone marrow 18

Visceral Leishmaniasis • • • 1903 1920 1931 William Leishman Pentavalent antimony Experimental transmission Leishmania donovani (Complex) L. d. archibaldi - L. d. chagasi - L. d. donovani - Ld. infantum 19

VL - Clinical Manifestation Variable - Incubation 3 -100+ weeks Lowgrade fever Hepato-splenomegaly Bone marrow hyperplasia Anemia, Leucopenia & Cachexia Hypergammaglobulinnemia Epistaxis , Proteinuria, Hematuria 20

• Profile view of a teenage boy suffering from visceral leishmaniasis. The boy exhibits splenomegaly, distended abdomen and severe muscle wasting. 21

• A 12 -year-old boy suffering from visceral leishmaniasis. The boy exhibits splenomegaly and severe muscle wasting. 22

• Jaundiced hands of a visceral leishmaniasis patient. 23

• Enlarged spleen and liver in an autopsy of an infant dying of visceral leishmaniasis. 24

Post Kala Azar Dermal Leishmanoid Normally develops <2 years after recovery Recrudescence Restricted to skin Rare but varies geographically 25

Cutaneous leishmaniasis of the face. 26

A cutaneous leishmaniasis lesion on the arm. 27

INFECTION Sub-clinical or inapparent infection Recovery Death Immune to reinfection Concurrent infection PKDL 28

Diagnosis Clinical signs & symptoms Hypergammaglobulinemia ELISA/Formol gel Bone marrow biopsy Spleen or liver biopsy Culture & Histology 29

Speciation • • Similar morphology Isoenzyme profiles - Zymodemes Monoclonal antibodies DNA hybridisation - PCR 30

Treatment Good nursing Diet Antibiotics Pentavalent antimony Pentamidine New drugs - New delivery 31

Control • • Vector control Reservoir control Treatment of active cases Vaccination 32