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Medical Flagellates

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

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  1. 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 donovani • Giardia lamblia • Trichomonas vaginalis

  3. Mobility Comparison Ameoba Trichomonas Giardia

  4. Lecture Topics on Leishmania • Introduction • The parasite and vector • The life-cycle • Clinical features • Diagnosis • Epidemiology • Chemotherapy

  5. Introduction Leishmaniasis 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 1845 - 1922 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.

  9. Phylum Order Family Genus Sarcomastigophora Kinetoplastida Trypanosomatidae Leishmania The Parasite

  10. Promasitogte Insect Motile Midgut Amastigote Mammalian stage Non-motile Intracellular Morphology Digenetic Life Cycle

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

  12. Promastigote

  13. Movement of Promastigote

  14. Electron photomicrograph of promastigotes

  15. EP promastigote rosette

  16. Amastigote

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

  18. A macrophage filled with Leishmania amastigotes.

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

  20. Sandflies

  21. Life Cycle Promastigote Amasitgote Transformation

  22. 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

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

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

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

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

  27. 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

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

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

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

  31. Jaundiced hands of a visceral leishmaniasis patient. 

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

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

  34. Cutaneous leishmaniasis of the face. 

  35. A cutaneous leishmaniasis lesion on the arm.

  36. INFECTION Sub-clinical or inapparent infection RecoveryDeath Immune to reinfection Concurrent infection PKDL

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

  38. Speciation • Similar morphology • DNA bouyant density • Isoenzyme profiles - Zymodemes • Monoclonal antibodies • DNA hybridisation - PCR

  39. 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。

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

  41. Control • Vector control • Reservoir control • Treatment of active cases • Vaccination

  42. Thank you

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