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Trypanosomiasis Sleeping Sickness

Trypanosomiasis Sleeping Sickness. David Humber. T.corvi Corvids T.cruzi Humans, rodents, marsupials T.brucei sp Man, ungulates T.lewisi Rodents T.musculis Rodents T.microti Voles T.dionisii Bats T.equiperdum Equids . Bone Marrow Heart muscle,

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Trypanosomiasis Sleeping Sickness

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  1. TrypanosomiasisSleeping Sickness David Humber

  2. T.corvi Corvids T.cruziHumans, rodents, marsupials T.brucei sp Man, ungulates T.lewisi Rodents T.musculis Rodents T.microti Voles T.dionisii Bats T.equiperdum Equids Bone Marrow Heart muscle, autonomic ganglia Blood Blood Blood Lymphoid tissue Heart muscle Genitals Trypanosomes of Vertebrates Species Host Site

  3. African Sleeping SicknessNganaSouth American Sleeping SicknessChagas Disease

  4. African Sleeping Sickness • Parasite - Trypanosoma brucei ssp • Trypanosoma brucei rhodesiense • Trypanosoma brucei gambiense • Vector - Tse Tse fly • Glossina mortisans (Eastern Africa) • Glossina palpalis (Western Africa)

  5. Lecture Topics • The Parasite & Vector • The Life Cycle • Clinical Features • Diagnosis • Epidemiology • Chemotherapy & Control • Vaccination

  6. Phylum Sub-Phylum Class Order Genus Mastigophora Sarcomastigophora Zoomastigophora Kinetoplastidae Trypanosoma Taxonomy ? species of mammals, birds, reptiles and amphibians

  7. The Parasite • Polymorphic spindle-shaped • Kinetoplast • Flagella & undulating membrane Trypomastigote Epimastigote

  8. African TrypanosomiasisThe Life Cycle Human Tse fly Trypomastigote Trypomastigote Stumpy Metacyclic Intermediate Epimastigote Slender Trypomastigote

  9. The Vectors Glossina 22 species - hatchet wing cell Shady habitat (20-30oC) Viviparous - 12 offspring Diurnal feeders (1mg/sec) Parasite development 10-14 days

  10. Animal Reservoirs Sub species now thought to be zoonotic Largely ungulates

  11. Virulence Reservoir Zoonotic Vector Distribution Less More Human/animal Human/animal Less More G.palpalis G.mortisans Western Africa Eastern Africa African Sleeping Sickness T.b.gambiense T.b.rhodesiense

  12. Clinical Features Primary chancre - resolves 2-3 weeks Initial symptoms - fever & headaches Day time sleeping Tremors & Convulsions Coma & Death Enlarged cervical lymph nodes (T.b.g) Winterbottoms sign

  13. Diagnosis • Direct microscopy • Blood (T.b.r.) • Lymph node aspirate (T.b.g.) • Lumbar puncture (Late T.b.r. & T.b.g.) • Serology • Animal inoculation

  14. Epidemiology 50 million at risk <20% under surveillance 20,000 new case/year Devastating epidemics 200 endemic foci

  15. Distribution

  16. Chemotherapy • Early stage - most recover • Suramin • Melasporol • Pentamidine • Late stage - upto 5% relapse • Only Melasporol • 10% encephalitis - 5% fatal

  17. Control Destruction of animal reservoir Vector Control Diagnosis & treatment

  18. Immunology • Antibody • Inteferon

  19. Parasitemia

  20. Variable Surface Glycoprotein 60kd (450aa) glycoprotein (CHO 7-17%) C-terminal anchored in membrane Often as a dimer (alpha helix) Densely clustered 107molecules/parasite Only epitopes in end third of N-terminal exposed Presented as topographical array T-independent antigen

  21. VSG Constant & Variable regions Random rearrangement of N terminal end (2/3) Almost no homology between V VSG’s Except cystein residues S-S bonds Switching not initiated by IR But selected

  22. Production of VSG Gene rearrangement Produces on expression linked copy (ELC) ELC transposed to telomeric end of chromosome - replacing existing gene Displaced gene lost Switch occurs every 106 divisions 100-1000 copie of different VSG’s in clone

  23. VSG Specific IR 3-4 days post infection strong IgM response Trypanosome disappear within hours VSG specific IgG appears - not relevant IgM response often >IgG After several cycles VSG abs vanish But abs to invariant ags remain elevated

  24. Trypanosome Elimination Antibody mediated Destruction by Kupffer cells Splenic macrophages minor role (cf malaria) Uptake - C3b - C3bi - direct? C mediated lysis not important Trypanosome destroyed within minutes

  25. Immunoregulation No secondary response to VSG’s unless cured by chemotherapy Failure of 1ry or 2ndry response prior to death Non specific polyclonal activation Suppresser Macrophages Failure of Ag presentation Anti idiotype responses

  26. Resistance and Virulence Spectrum of disease T. brucei sub species Host differences Independant of VSG

  27. Vaccination Effective Antibody response Phagocytosis & killing but Cyclical parasitemia Antigenic variation not predicable

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