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Edit Comment Close Premium member Presentation Transcript TrypanosomiasisSleeping Sickness: Trypanosomiasis Sleeping Sickness David HumberTrypanosomes of Vertebrates: Trypanosomes of Vertebrates 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, autonomic ganglia Blood Blood Blood Lymphoid tissue Heart muscle Genitals Species Host SiteAfrican Sleeping SicknessNganaSouth American Sleeping SicknessChagas Disease: African Sleeping Sickness Ngana South American Sleeping Sickness Chagas Disease African Sleeping Sickness: 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)Lecture Topics: Lecture Topics The Parasite & Vector The Life Cycle Clinical Features Diagnosis Epidemiology Chemotherapy & Control VaccinationTaxonomy: Taxonomy Phylum Sub-Phylum Class Order Genus Mastigophora Sarcomastigophora Zoomastigophora Kinetoplastidae Trypanosoma ? species of mammals, birds, reptiles and amphibiansThe Parasite: The Parasite Polymorphic spindle-shaped Kinetoplast Flagella & undulating membrane Trypomastigote EpimastigoteAfrican TrypanosomiasisThe Life Cycle: African Trypanosomiasis The Life Cycle Human Tse fly Trypomastigote Trypomastigote Stumpy Metacyclic Intermediate Epimastigote Slender Trypomastigote The Vectors: The Vectors Glossina 22 species - hatchet wing cell Shady habitat (20-30oC) Viviparous - 12 offspring Diurnal feeders (1mg/sec) Parasite development 10-14 daysAnimal Reservoirs: Animal Reservoirs Sub species now thought to be zoonotic Largely ungulatesAfrican Sleeping Sickness: African Sleeping Sickness Virulence Reservoir Zoonotic Vector Distribution Less More Human/animal Human/animal Less More G.palpalis G.mortisans Western Africa Eastern Africa T.b.gambiense T.b.rhodesienseClinical Features: 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 signDiagnosis: Diagnosis Direct microscopy Blood (T.b.r.) Lymph node aspirate (T.b.g.) Lumbar puncture (Late T.b.r. & T.b.g.) Serology Animal inoculationEpidemiology: Epidemiology 50 million at risk <20% under surveillance 20,000 new case/year Devastating epidemics 200 endemic fociDistribution: DistributionChemotherapy: Chemotherapy Early stage - most recover Suramin Melasporol Pentamidine Late stage - upto 5% relapse Only Melasporol 10% encephalitis - 5% fatalControl: Control Destruction of animal reservoir Vector Control Diagnosis & treatmentImmunology: Immunology Antibody Inteferon Parasitemia: ParasitemiaVariable Surface Glycoprotein: 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 VSG: 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 Production of VSG: 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 cloneVSG Specific IR: 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 Trypanosome Elimination: 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 Immunoregulation: 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 Resistance and Virulence: Resistance and Virulence Spectrum of disease T. brucei sub species Host differences Independant of VSGVaccination: Vaccination Effective Antibody response Phagocytosis & killing but Cyclical parasitemia Antigenic variation not predicable You do not have the permission to view this presentation. In order to view it, please contact the author of the presentation.
african trypanosomes Tibald Download Post to : URL : Related Presentations : Share Add to Flag Embed Email Send to Blogs and Networks Add to Channel Uploaded from authorPOINTLite Insert YouTube videos in PowerPont slides with aS Desktop Copy embed code: (To copy code, click on the text box) Embed: URL: Thumbnail: WordPress Embed Customize Embed The presentation is successfully added In Your Favorites. Views: 2844 Category: Education License: All Rights Reserved Like it (1) Dislike it (0) Added: January 11, 2008 This Presentation is Public Favorites: 1 Presentation Description No description available. Comments Posting comment... By: OKONJI (9 month(s) ago) am requesting for ahance to observe the slides Saving..... Post Reply Close Saving..... Edit Comment Close By: OKONJI (9 month(s) ago) beatiful presantation Saving..... Post Reply Close Saving..... Edit Comment Close By: juyal (27 month(s) ago) good presentation........should hav added sum pics too Saving..... 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Edit Comment Close Premium member Presentation Transcript TrypanosomiasisSleeping Sickness: Trypanosomiasis Sleeping Sickness David HumberTrypanosomes of Vertebrates: Trypanosomes of Vertebrates 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, autonomic ganglia Blood Blood Blood Lymphoid tissue Heart muscle Genitals Species Host SiteAfrican Sleeping SicknessNganaSouth American Sleeping SicknessChagas Disease: African Sleeping Sickness Ngana South American Sleeping Sickness Chagas Disease African Sleeping Sickness: 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)Lecture Topics: Lecture Topics The Parasite & Vector The Life Cycle Clinical Features Diagnosis Epidemiology Chemotherapy & Control VaccinationTaxonomy: Taxonomy Phylum Sub-Phylum Class Order Genus Mastigophora Sarcomastigophora Zoomastigophora Kinetoplastidae Trypanosoma ? species of mammals, birds, reptiles and amphibiansThe Parasite: The Parasite Polymorphic spindle-shaped Kinetoplast Flagella & undulating membrane Trypomastigote EpimastigoteAfrican TrypanosomiasisThe Life Cycle: African Trypanosomiasis The Life Cycle Human Tse fly Trypomastigote Trypomastigote Stumpy Metacyclic Intermediate Epimastigote Slender Trypomastigote The Vectors: The Vectors Glossina 22 species - hatchet wing cell Shady habitat (20-30oC) Viviparous - 12 offspring Diurnal feeders (1mg/sec) Parasite development 10-14 daysAnimal Reservoirs: Animal Reservoirs Sub species now thought to be zoonotic Largely ungulatesAfrican Sleeping Sickness: African Sleeping Sickness Virulence Reservoir Zoonotic Vector Distribution Less More Human/animal Human/animal Less More G.palpalis G.mortisans Western Africa Eastern Africa T.b.gambiense T.b.rhodesienseClinical Features: 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 signDiagnosis: Diagnosis Direct microscopy Blood (T.b.r.) Lymph node aspirate (T.b.g.) Lumbar puncture (Late T.b.r. & T.b.g.) Serology Animal inoculationEpidemiology: Epidemiology 50 million at risk <20% under surveillance 20,000 new case/year Devastating epidemics 200 endemic fociDistribution: DistributionChemotherapy: Chemotherapy Early stage - most recover Suramin Melasporol Pentamidine Late stage - upto 5% relapse Only Melasporol 10% encephalitis - 5% fatalControl: Control Destruction of animal reservoir Vector Control Diagnosis & treatmentImmunology: Immunology Antibody Inteferon Parasitemia: ParasitemiaVariable Surface Glycoprotein: 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 VSG: 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 Production of VSG: 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 cloneVSG Specific IR: 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 Trypanosome Elimination: 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 Immunoregulation: 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 Resistance and Virulence: Resistance and Virulence Spectrum of disease T. brucei sub species Host differences Independant of VSGVaccination: Vaccination Effective Antibody response Phagocytosis & killing but Cyclical parasitemia Antigenic variation not predicable