1. Trypanosomiasis Sleeping Sickness David Humber

2. Trypanosomes of Vertebrates T.corvi Corvids T.cruzi Humans, rodents, marsupials T.brucei spMan, ungulates T.lewisiRodents T.musculisRodents T.microtiVoles T.dionisiiBats T.equiperdum Equids Bone Marrow Heart muscle, autonomic ganglia Blood Lymphoid tissue Heart muscle Genitals SpeciesHostSite

3. African Sleeping Sickness Ngana South American Sleeping Sickness Chagas Disease

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

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

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

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

8. African Trypanosomiasis The Life Cycle HumanTse flyTrypomastigote StumpyMetacyclic IntermediateEpimastigote SlenderTrypomastigote

9. The Vectors Glossina 22 species - hatchet wing cell Shady habitat (20-30 o C) 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. African Sleeping Sickness b Virulence b Reservoir b Zoonotic b Vector b Distribution Less More Human/animal Less More G.palpalis G.mortisans Western Africa Eastern Africa 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 b Direct microscopy Blood (T.b.r.) Lymph node aspirate (T.b.g.) Lumbar puncture (Late T.b.r. & T.b.g.) b Serology b 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 b Early stage - most recover Suramin Melasporol Pentamidine b Late stage - upto 5% relapse Only Melasporol –10% encephalitis - 5% fatal

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

18. Immunology b Antibody b 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 10 7 molecules/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 10 6 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