african trypanosomes

8/8/2019 African Trypanosomes

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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

african trypanosomes

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