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Trypanosomiasis
Sleeping Sickness
David Humber
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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 Site
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African Sleeping Sickness
Ngana
SouthAmerican Sleeping Sickness
Chagas Disease
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Lecture Topics
The Parasite & Vector
The Life Cycle Clinical Features
Diagnosis
Epidemiology Chemotherapy & Control
Vaccination
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The Parasite
Polymorphic spindle-shaped
Kinetoplast Flagella & undulating membrane
Trypomastigote
Epimastigote
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African TrypanosomiasisThe Life Cycle
Human Tse fly
Trypomastigote Trypomastigote
Stumpy Metacyclic
Intermediate Epimastigote
Slender Trypomastigote
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The Vectors
Glossina
22 species - hatchet wing cellShady habitat (20-30oC)
Viviparous - 12 offspring
Diurnal feeders (1mg/sec)Parasite development 10-14 days
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Animal Reservoirs
Sub species now thought to be zoonotic
Largely ungulates
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African Sleeping Sickness
Virulence
Reservoir
Zoonotic
Vector
Distribution
Less More
Human/animal Human/animal
Less More
G.palpalis G.mortisans
WesternAfrica EasternAfrica
T.b.gambiense T.b.rhodesiense
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Clinical Features
Primary chancre - resolves 2-3 weeks
Initial symptoms - fever & headachesDay time sleeping
Tremors & Convulsions
Coma & Death
Enlarged cervical lymph nodes (T.b.g)
Winterbottoms sign
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Epidemiology
50 million at risk
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Chemotherapy
Early stage - most recover
Suramin
Melasporol
Pentamidine
Late stage - upto 5% relapse
Only Melasporol
10% encephalitis - 5% fatal
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Control
Destruction of animal reservoir
Vector ControlDiagnosis & treatment
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Immunology
Antibody
Inteferon
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ParasitemiaParasitemia in African Sleeping
Sickness
0
2
4
6
8
10
0 10 20 30
Days after Infection
Log1
0
rypanosomesp
er
ml
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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 exposedPresented as topographical array
T-independent antigen
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VSG
Constant & Variable regions
Random rearrangement of N terminal end (2/3)
Almost no homology between V VSGs
Except cystein residues S-S bonds
Switching not initiated by IRBut selected
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VSG SpecificIR
3-4 days post infection strongIgM response
Trypanosome disappear within hours
VSG specificIgG appears - not relevant
IgM response often >IgG
After several cycles VSG abs vanish
But abs to invariant ags remain elevated
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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
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Immunoregulation
No secondary response to VSGs unless cured by
chemotherapy
Failure of 1ry or 2ndry response prior to death
Non specific polyclonal activation
Suppresser Macrophages
Failure ofAg presentation
Anti idiotype responses
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Resistance and Virulence
Spectrum of disease
T. brucei sub species
Host differences
Independant of VSG
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Vaccination
EffectiveAntibody response
Phagocytosis & killing
but
Cyclical parasitemia
Antigenic variation not predicable