Trypanosomiasis

Sleeping Sickness

David Humber
 Trypanosomes of Vertebrates
Species Host Site
T.corvi Corvids Bone Marrow
T.cruzi Humans, rodents, Heart muscle,
marsupials autonomic ganglia
T.brucei sp Man, ungulates Blood
T.lewisi Rodents Blood
T.musculis Rodents Blood
T.microti Voles Lymphoid tissue
T.dionisii Bats Heart muscle
T.equiperdum Equids Genitals
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 Mastigophora
 Sub-Phylum Sarcomastigophora
 Class Zoomastigophora
 Order Kinetoplastidae
 Genus 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 (20-30oC)
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
T.b.gambiense T.b.rhodesiense

 Virulence Less More

 Reservoir Human/animal Human/animal
 Zoonotic Less More
 Vector G.palpalis G.mortisans
 Distribution Western Africa Eastern Africa
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
Log 10 Trypanosom es per

10

6
ml

0
0 10 20 30
Days after Infection
 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

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

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 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 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

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