Medical FlagellatesMedical Flagellates

山东大学 医学院山东大学 医学院病原生物学研究所 寄生虫学教研室病原生物学研究所 寄生虫学教研室

何深一 何深一 MD, Ph.D.MD, Ph.D.

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FlagellatesFlagellates

• Leishmania Leishmania donovanidonovani

• Giardia lambliaGiardia lamblia

• Trichomonas Trichomonas vaginalis vaginalis

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TrichomonasTrichomonas GiardiaGiardia

AmeobaAmeoba

Mobility ComparisonMobility Comparison

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Lecture Topics on Lecture Topics on LeishmaniaLeishmania

• IntroductionIntroduction• The parasite and vectorThe parasite and vector• The life-cycleThe life-cycle• Clinical featuresClinical features• DiagnosisDiagnosis• EpidemiologyEpidemiology• ChemotherapyChemotherapy

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IntroductionIntroduction

LeishmaniasisLeishmaniasisProtozoal disease of mammalsProtozoal disease of mammalsLargely zoonoticLargely zoonotic23+ pathogenic species23+ pathogenic species

Visceral Leishmaniasis Visceral Leishmaniasis Mucocutaneous leishmaniasisMucocutaneous leishmaniasisCutaneous leishmaniasisCutaneous leishmaniasis

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Species Pathogenic in Species Pathogenic in HumansHumans

Leishmania donovani (Laveran 1903)Leishmania donovani (Laveran 1903) (VL) (VL)

Leishmania tropica (CL)Leishmania tropica (CL)

Leishmania major (CL)Leishmania major (CL)

Leishmania aethiopica (CL)Leishmania aethiopica (CL)

Leishmania mexicana (CL)Leishmania mexicana (CL)

Leishmania brazilliensis (MCL)Leishmania brazilliensis (MCL)

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Charles Louis Alphonse Charles Louis Alphonse LaveranLaveran

France France

Institute Pasteur Institute Pasteur Paris, France Paris, France

1845 - 19221845 - 1922The Nobel Prize in

Physiology or Medicine 1907

"in recognition of his work on the role played by protozoa in causing diseases"

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

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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

• The individual The individual amastigotes amastigotes measure measure approximately 3 approximately 3 µm in diameter. µm in diameter. 

• The promastigotes The promastigotes

are approximately are approximately 25 µm in length.   25 µm in length.  

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PromastigotePromastigote

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Movement of Movement of PromastigotePromastigote

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Electron Electron photomicrograph of photomicrograph of

promastigotespromastigotes

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EP promastigote EP promastigote rosetterosette

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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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• A macrophage filled with Leishmania amastigotes.

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VectorsVectors

Phlebotomine SandfliesPhlebotomine Sandflies

6 genera world wide distribution6 genera world wide distribution

500 species500 species

Females HaematophagusFemales Haematophagus

Males sap feedersMales sap feeders

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SandfliesSandflies

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Life CycleLife Cycle

PromastigotePromastigote Amasitgote Amasitgote TransformationTransformation

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Life CycleLife Cycle

• 1  1  infective stage: promastigotesinfective stage: promastigotes• 2  mode of infection:  biten by sandfly2  mode of infection:  biten by sandfly• 3  site of habitation:  macrophages 3  site of habitation:  macrophages • 4  pathogenic stage:  amastigotes4  pathogenic stage:  amastigotes• 5  diagnostic stage:  amastigotes5  diagnostic stage:  amastigotes• 6 6 reservoir host: dogsreservoir host: dogs

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Mammalian HostsMammalian Hosts

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

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

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Clinical DiseaseClinical Disease

• VisceralVisceral• Fatal (90% Fatal (90%

untreated)untreated)• LiverLiver• SpleenSpleen• Bone marrowBone marrow

• CutaneousCutaneous• Generally Self- healing Generally Self- healing • SkinSkin• Mucous membranesMucous membranes

SPECTRUM OF DISEASESPECTRUM OF DISEASE

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Initial InfectionInitial Infection

• Similar in all speciesSimilar in all species• Inoculation of promastigotesInoculation of promastigotes• Inflammation & chemotaxisInflammation & chemotaxis• Receptor mediated phagocytosisReceptor mediated phagocytosis

PromastigotePromastigote Amasitgote Amasitgote TransformationTransformation

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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 Death Immune 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• DNA bouyant densityDNA bouyant density• Isoenzyme profiles - ZymodemesIsoenzyme profiles - Zymodemes• Monoclonal antibodiesMonoclonal antibodies• DNA hybridisation - PCRDNA hybridisation - PCR

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

2. 2. 我国：长江以北我国：长江以北 1616 个省市自治区，甘肃、四川、陕西、山西、个省市自治区，甘肃、四川、陕西、山西、新疆和内蒙古更多见。新疆和内蒙古更多见。

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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

49Thank youThank you