Trypanosomiasis

Sleeping Sickness


David Humber
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
African Sleeping Sickness
Ngana

South American Sleeping Sickness
Chagas 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
Mastigophora
Sarcomastigophora
Zoomastigophora
Kinetoplastidae
Trypanosoma
? species of mammals, birds, reptiles and amphibians
The Parasite
Polymorphic spindle-shaped
Kinetoplast
Flagella & undulating membrane
Trypomastigote
Epimastigote
African Trypanosomiasis
The Life Cycle
Human Tse fly

Trypomastigote Trypomastigote
Stumpy Metacyclic
Intermediate Epimastigote
Slender Trypomastigote
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
Animal Reservoirs
Sub species now thought to be zoonotic
Largely ungulates
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.rhodesiense
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
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/year
Devastating 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 reservoir
Vector 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
L
o
g

1
0

T
r
y
p
a
n
o
s
o
m
e
s

p
e
r

m
l
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

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 IR
But selected


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 VSGs in clone
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
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
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 of Ag presentation
Anti idiotype responses


Resistance and Virulence
Spectrum of disease
T. brucei sub species
Host differences
Independant of VSG
Vaccination
Effective Antibody response
Phagocytosis & killing
but
Cyclical parasitemia
Antigenic variation not predicable