Medical Flagellates 山东大学 医学院 病原生物学研究所 寄生虫学教研室 何深一 MD, Ph.D.

2 Flagellates Leishmania donovaniLeishmania donovani Giardia lambliaGiardia lamblia Trichomonas vaginalisTrichomonas vaginalis

3 TrichomonasGiardia Ameoba Mobility Comparison

4 Lecture Topics on Leishmania IntroductionIntroduction The parasite and vectorThe parasite and vector The life-cycleThe life-cycle Clinical featuresClinical features DiagnosisDiagnosis EpidemiologyEpidemiology ChemotherapyChemotherapy

5IntroductionLeishmaniasis Protozoal disease of mammals Largely zoonotic 23+ pathogenic species Visceral Leishmaniasis Mucocutaneous leishmaniasis Cutaneous leishmaniasis

6 Species Pathogenic in Humans Leishmania donovani (Laveran 1903) (VL) Leishmania tropica (CL) Leishmania major (CL) Leishmania aethiopica (CL) Leishmania mexicana (CL) Leishmania brazilliensis (MCL)

7 Charles Louis Alphonse Laveran France Institute Pasteur Paris, France The Nobel Prize in Physiology or Medicine 1907 "in recognition of his work on the role played by protozoa in causing diseases"

8 Leishmaniasis is prevalent world wide: ranging from south east Asia, Indo-Pakistan, Mediterranean, north and central Africa, and south and central America. Leishmaniasis is prevalent world wide: ranging from south east Asia, Indo-Pakistan, Mediterranean, north and central Africa, and south and central America.

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11 The Parasite PhylumPhylum OrderOrder FamilyFamily GenusGenusSarcomastigophoraKinetoplastidaTrypanosomatidaeLeishmania

12 Morphology PromasitogtePromasitogte InsectInsect MotileMotile MidgutMidgut Amastigote Amastigote Mammalian stageMammalian stage Non-motileNon-motile IntracellularIntracellular Digenetic Life Cycle

13 Morphology The individual amastigotes measure approximately 3 µm in diameter.The individual amastigotes measure approximately 3 µm in diameter. The promastigotes are approximately 25 µm in length.The promastigotes are approximately 25 µm in length.

14 Promastigote

15 Movement of Promastigote

16 Electron photomicrograph of promastigotes

17 EP promastigote rosette

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19 Amastigote

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

21 A macrophage filled with Leishmania amastigotes.

22 Vectors Phlebotomine Sandflies 6 genera world wide distribution 500 species Females Haematophagus Males sap feeders

23 Sandflies

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Life Cycle Promastigote Amasitgote Transformation Transformation

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Life Cycle 1 infective stage: promastigotes1 infective stage: promastigotes 2 mode of infection: biten by sandfly2 mode of infection: biten by sandfly 3 site of habitation: macrophages3 site of habitation: macrophages 4 pathogenic stage: amastigotes4 pathogenic stage: amastigotes 5 diagnostic stage: amastigotes5 diagnostic stage: amastigotes 6 reservoir host: dogs6 reservoir host: dogs

28 Mammalian Hosts RodentsRodents GerbilsGerbils HyraxesHyraxes BatsBats PorcupinesPorcupines OpossumsOpossums Sloths Sloths Primates Primates Dogs Dogs Foxes Foxes Anteaters Anteaters

29 Clinical Disease VisceralVisceral Fatal (90% untreated)Fatal (90% untreated) LiverLiver SpleenSpleen Bone marrowBone marrow Cutaneous Cutaneous Generally Self- healingGenerally Self- healing SkinSkin Mucous membranesMucous membranes SPECTRUM OF DISEASE

30 Initial Infection Similar in all speciesSimilar in all species Inoculation of promastigotesInoculation of promastigotes Inflammation & chemotaxisInflammation & chemotaxis Receptor mediated phagocytosisReceptor mediated phagocytosis Promastigote Amasitgote Transformation Transformation

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

32 Visceral Leishmaniasis William Leishman Pentavalent antimony Experimental transmission Leishmania donovani (Complex) L.d. archibaldi - L.d.chagasi - L.d.donovani - Ld.infantum

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

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

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

37 Jaundiced hands of a visceral leishmaniasis patient.

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

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

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41 Cutaneous leishmaniasis of the face.

42 A cutaneous leishmaniasis lesion on the arm.

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

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

45 Speciation Similar morphologySimilar morphology DNA bouyant densityDNA bouyant density Isoenzyme profiles - ZymodemesIsoenzyme profiles - Zymodemes Monoclonal antibodiesMonoclonal antibodies DNA hybridisation - PCRDNA hybridisation - PCR

46 1. Leishmaniasis is prevalent world wide: ranging from south east Asia, Indo-Pakistan, Mediterranean, north and central Africa, and south and central America. 2. 我国：长江以北 16 个省市自治区，甘肃、四川、陕西、山西、 新疆和内蒙古更多见。

47 Treatment Good nursing DietAntibiotics Pentavalent antimony Pentamidine New drugs - New delivery

48 Control Vector controlVector control Reservoir controlReservoir control Treatment of active casesTreatment of active cases VaccinationVaccination

49 Thank you