Trypanosomiasis Sleeping Sickness David Humber
TrypanosomiasisSleeping Sickness
David Humber
Trypanosomes of Vertebrates
T.corvi Corvids
T.cruzi Humans, rodents, marsupials
T.brucei sp Man, ungulatesT.lewisi RodentsT.musculis RodentsT.microti VolesT.dionisii BatsT.equiperdum Equids
Bone MarrowHeart muscle, autonomic
gangliaBloodBloodBloodLymphoid tissueHeart muscleGenitals
Species Host Site
African Sleeping SicknessNgana
South American Sleeping SicknessChagas Disease
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
The Parasite & Vector The Life Cycle Clinical Features Diagnosis Epidemiology Chemotherapy & Control Vaccination
Taxonomy
Phylum Sub-Phylum Class Order Genus
MastigophoraSarcomastigophoraZoomastigophoraKinetoplastidaeTrypanosoma
? species of mammals, birds, reptiles and amphibians
The Parasite
Polymorphic spindle-shaped Kinetoplast Flagella & undulating membrane
TrypomastigoteEpimastigote
African TrypanosomiasisThe Life Cycle
Human Tse fly
Trypomastigote TrypomastigoteStumpy MetacyclicIntermediate EpimastigoteSlender Trypomastigote
The Vectors
Glossina22 species - hatchet wing cell
Shady habitat (20-30oC)Viviparous - 12 offspring
Diurnal feeders (1mg/sec)Parasite development 10-14 days
Animal Reservoirs
Sub species now thought to be zoonotic
Largely ungulates
African Sleeping Sickness
Virulence Reservoir Zoonotic Vector Distributi
on
Less MoreHuman/animal
Human/animalLess MoreG.palpalis
G.mortisansWestern Africa Eastern
Africa
T.b.gambiense T.b.rhodesiense
Clinical Features
Primary chancre - resolves 2-3 weeks
Initial symptoms - fever & headaches
Day time sleepingTremors & Convulsions
Coma & DeathEnlarged cervical lymph nodes (T.b.g)Winterbottoms sign
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
Epidemiology
50 million at risk<20% under surveillance
20,000 new case/yearDevastating epidemics
200 endemic foci
Distribution
Chemotherapy
Early stage - most recover• Suramin• Melasporol• Pentamidine
Late stage - upto 5% relapse• Only Melasporol
– 10% encephalitis - 5% fatal
Control
Destruction of animal reservoirVector Control
Diagnosis & treatment
Immunology
Antibody Inteferon
Parasitemia
Parasitemia in African Sleeping Sickness
0
2
4
6
8
10
0 10 20 30
Days after Infection
Lo
g 1
0 T
ryp
ano
so
me
s p
er
ml
Variable Surface Glycoprotein
60kd (450aa) glycoprotein (CHO 7-17%) C-terminal anchored in membrane
Often as a dimer (alpha helix)Densely clustered 107molecules/parasiteOnly epitopes in end third of N-terminal
exposedPresented as topographical array
T-independent antigen
VSG
Constant & Variable regionsRandom rearrangement of N terminal end
(2/3)Almost no homology between V VSG’s
Except cystein residues S-S bondsSwitching not initiated by IR
But selected
Production of VSG
Gene rearrangementProduces on expression linked copy (ELC)
ELC transposed to telomeric end of chromosome - replacing existing gene
Displaced gene lostSwitch occurs every 106 divisions
100-1000 copie of different VSG’s in clone
VSG Specific IR
3-4 days post infection strong IgM response
Trypanosome disappear within hoursVSG specific IgG appears - not relevant
IgM response often >IgGAfter several cycles VSG abs vanish
But abs to invariant ags remain elevated
Trypanosome Elimination
Antibody mediatedDestruction by Kupffer cells
Splenic macrophages minor role (cf malaria)
Uptake - C3b - C3bi - direct?C mediated lysis not important
Trypanosome destroyed within minutes
Immunoregulation
No secondary response to VSG’s unless cured by chemotherapy
Failure of 1ry or 2ndry response prior to death
Non specific polyclonal activationSuppresser MacrophagesFailure of Ag presentationAnti idiotype responses
Resistance and Virulence
Spectrum of diseaseT. brucei sub species
Host differencesIndependant of VSG
Vaccination
Effective Antibody responsePhagocytosis & killing
butCyclical parasitemia
Antigenic variation not predicable