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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. Flagellates. Leishmania donovani Giardia lamblia Trichomonas vaginalis . Mobility Comparison. Ameoba. Trichomonas. Giardia. Lecture Topics on Leishmania. Introduction The parasite and vector The life-cycle
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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.
Flagellates • Leishmania donovani • Giardia lamblia • Trichomonas vaginalis
Mobility Comparison Ameoba Trichomonas Giardia
Lecture Topics on Leishmania • Introduction • The parasite and vector • The life-cycle • Clinical features • Diagnosis • Epidemiology • Chemotherapy
Introduction Leishmaniasis Protozoal disease of mammals Largely zoonotic 23+ pathogenic species Visceral Leishmaniasis Mucocutaneous leishmaniasis Cutaneous leishmaniasis
Species Pathogenic in Humans Leishmania donovani (Laveran 1903) (VL) Leishmania tropica (CL) Leishmania major (CL) Leishmania aethiopica (CL) Leishmania mexicana (CL) Leishmania brazilliensis (MCL)
Charles Louis Alphonse Laveran France Institute Pasteur Paris, France 1845 - 1922 The Nobel Prize in Physiology or Medicine 1907 "in recognition of his work on the role played by protozoa in causing diseases"
Leishmaniasis is prevalent world wide: ranging from south east Asia, Indo-Pakistan, Mediterranean, north and central Africa, and south and central America.
Phylum Order Family Genus Sarcomastigophora Kinetoplastida Trypanosomatidae Leishmania The Parasite
Promasitogte Insect Motile Midgut Amastigote Mammalian stage Non-motile Intracellular Morphology Digenetic Life Cycle
Morphology • The individual amastigotes measure approximately 3 µm in diameter. • The promastigotes are approximately 25 µm in length.
Amastigotes of Leishmania in a macrophage from a lymph node of a dog.
Vectors Phlebotomine Sandflies 6 genera world wide distribution 500 species Females Haematophagus Males sap feeders
Life Cycle Promastigote Amasitgote Transformation
Life Cycle • 1 infective stage: promastigotes • 2 mode of infection: biten by sandfly • 3 site of habitation: macrophages • 4 pathogenic stage: amastigotes • 5 diagnostic stage: amastigotes • 6 reservoir host: dogs
Rodents Gerbils Hyraxes Bats Porcupines Opossums Sloths Primates Dogs Foxes Anteaters . . . . . Mammalian Hosts
Visceral Fatal (90% untreated) Liver Spleen Bone marrow Cutaneous Generally Self- healing Skin Mucous membranes Clinical Disease SPECTRUM OF DISEASE
Initial Infection • Similar in all species • Inoculation of promastigotes • Inflammation & chemotaxis • Receptor mediated phagocytosis Promastigote Amasitgote Transformation
Parasite Spread Macrophage lysis & parasite release Lymphatic spread Blood spread Target organs Skin/lymph nodes/spleen/liver/ bone marrow
1903 1920 1931 William Leishman Pentavalent antimony Experimental transmission Visceral Leishmaniasis Leishmania donovani (Complex) L.d. archibaldi - L.d.chagasi - L.d.donovani - Ld.infantum
VL - Clinical Manifestation Variable - Incubation 3-100+ weeks Lowgrade fever Hepato-splenomegaly Bone marrow hyperplasia Anemia, Leucopenia & Cachexia Hypergammaglobulinnemia Epistaxis , Proteinuria, Hematuria
Profile view of a teenage boy suffering from visceral leishmaniasis. The boy exhibits splenomegaly, distended abdomen and severe muscle wasting.
A 12-year-old boy suffering from visceral leishmaniasis. The boy exhibits splenomegaly and severe muscle wasting.
Enlarged spleen and liver in an autopsy of an infant dying of visceral leishmaniasis.
Post Kala Azar Dermal Leishmanoid Normally develops <2 years after recovery Recrudescence Restricted to skin Rare but varies geographically
INFECTION Sub-clinical or inapparent infection RecoveryDeath Immune to reinfection Concurrent infection PKDL
Diagnosis Clinical signs & symptoms Hypergammaglobulinemia ELISA/Formol gel Bone marrow biopsy Spleen or liver biopsy Culture & Histology
Speciation • Similar morphology • DNA bouyant density • Isoenzyme profiles - Zymodemes • Monoclonal antibodies • DNA hybridisation - PCR
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。
Treatment Good nursing Diet Antibiotics Pentavalent antimony Pentamidine New drugs - New delivery
Control • Vector control • Reservoir control • Treatment of active cases • Vaccination