Human African Trypanosomiasis (HAT)

Domain - Eukaryota
1. Kindom - Excavata (unicellular)
  1. Phylum - Eugenozoa (flagellate)
    1. Class - Kinetoplastida (kinetoplast-has mitochondrial genome)
      1. Order - Trypanosomatida (cork screw motion)
        Genus - Trypanosoma and Leishmania
        Species - brucei (African sleeping sickness), cruzi (chagas disease) Leishmania species (Leishmania)
Found in 36 Sub-Saharan African countries
1. 60 million people at risk
2. Common is rural popilations
3. Prevalence 20- 50%
4. Zoonotic and anthropomorphic transmission
5. Epidemics
  1. 1990s - due to political unrest (fewer people screened)
  2. 2000s - implication of diagnostic program and vector control
Found in saliva of tsete fly (Glossina species)
1. Very painful bite
2. Both male and female flies carry parasite
  1. Females are viviparous
    1. Deposits a fully developed larvae
    2. Burrows into the soil
      1. Pupates
        Emerges as an adult fly 1 month later
        Newly hatched flies are not infected with Trypanosomes
  2. Males are multivoltine
    1. Typically produce 4 generations per year
      1. Up to 31 lifespans per year
3. 34 different species and sub-species
4. Split on 3 groups depending on distribution, behaviour, molecular and morphology
  1. Riverine
  2. Savannah
  3. Forest
  4. Different groups have ability to transmit different HAT forms
T. brucei
1. Structure
  1. Has one single mitochondria
  2. Contains glycosomes (for glycolysis)
  3. ER and Golgi
  4. Nucleus
  5. Flagellum
  6. Flagella pocket (endo/exocytosis)
2. Parasites
  1. Mostly found in insects - some heteroxenous (have secondary hosts)
3. Protozoa
4. Major forms
  1. Tropomastigote
    1. Common morphology in mammals and insects
    2. Common morphology of infective forms
    3. Flagella pocket posterier to nucelus
      1. Flagella attached to cell via undulating membrane
    4. Kinetoplast (circular network of DNA inside a mitochondrion) - located between nucleus and posterior end
    5. Procyclic tropmastigote - insect
      1. 10-30 um by 1-3 um
      2. Single flagellum - motile
      3. Division by binary fission
      4. Procyclin cell coat
    6. Bloodstream tropomastigote - mammal
      1. 10-30 um by 1-3 um
      2. Single flagellum - highly motile
      3. Division by binary fission
      4. Extracellular parasite
      5. Cell coat
    7. Metacyclic tropomastigote - insect to humans
      1. 10-30 um by 1-3 um
      2. Single flagellum -highly motile
      3. Unable to divide
    8. Short stumpy tropomastigote - humans to insect
      1. Same as metacyclic tropomastigote
  2. Epimastigote
    1. Common morphology in insect salivary gland
    2. Flagellum pocket located between nucleus and anterior end
    3. Kinetoplast located between nucleus and anterior end
5. Life Cycle
  1. Tsetse fly takes a blood meal - injects metacyclic tropomastigotes
    1. Transform into bloodstream form (BSF) tropomastigotes and are carried to other sites
      1. Multiply by binary fission in bodily fluids
        Tropomastigotes present in blood
        Tsetse fly takes a blood meal - tropomastigotes are injested
        Transform into procyclic tropomastigotes in midgut
        Replicate by binary fission
        Leave the midgut and transform into epimastigotes
        Multiply in salivary gland and transform into metacyclic tropomastigotes
        Bind to epithelial cells via flagella and divide by binary fission
        Sexual reproduction can occur but genetic exchange is not essential
        All BSF tropomastigotes die
        Transform into short stumpy (SS) form - trigger unknown. Stumpy induction factor?
      2. Potentially triggered by temperature
Types
1. East African Trypanosomiasis
  1. Trypanosoma brucei rhodensiense
  2. Tsetse fly inhabits the savannah
  3. Zoonotic transmission - ungulate to human
  4. Non-human reservoirs rare
  5. Asymptomatic carries rare
  6. Parasitaemia high
  7. Rapid progression to death
2. West African Trypanosomiasis
  1. Trypanosoma brucei gambiense
  2. Tsetse fly inhabits the riverine
  3. Anthropomorphic transmission - human to human
  4. Reservoirs in wild and domestic animals
  5. Asymptomatic carriers common
  6. Parasitaemia low
  7. Slow progression to death
  8. Can cause endemics
3. Other African Trypanosomiasis - found predominately in ungulate (hooved) animals
  1. Trypanosoma brucei brucei
  2. Trypanosoma vivax
  3. Trypanosoma congolense
Pathology
1. Early stage - blood
  1. Chancre (painless ulceration) at site of bite in 50% of T,b, rhodesience cases
    1. Can heal, leaving altered pigment
  2. Intermittent fever and headaches
  3. Lymphatic
    1. Continued febrile (feverish) episodes
    2. Lymphadenopathy
      1. Winterbottom's sign (enlarged neck gland)
    3. Deteriorating health
    4. Late stage - CNS
      1. Anorexia
      2. Neurological symptoms
      3. Apathy and lassitude
      4. Sleep disturbance
      5. Convulsions, coma and death
        WAT takes months-years
        EAT takes weeks-months
Diagnosis
1. Direct method - microscopy
  1. Blood smear
  2. CSF analysis
  3. Enrichment
    1. Microhaematocrit (buffy coat)
    2. DEAE anion exchange column (RBCs stay in column, parasites pass through)
2. Indirect method - seriology
  1. Card agglutination test for trypanosomiasis (CATT)
    1. Only works for T.b. gambiense but only costs 25 cents per test
  2. Put a drop of blood on card with some fixed parasites
    1. Agglutination (blue granular deposits) indicate infection
Treatment
1. Suramin
2. Pentamidine
3. Melarsoprol
4. Eflornithine
5. NECT (nifurtimox-eflornithine combination therapy)
Prevention and Control
1. Pre-20th century - humans did not settle/cultivate where flies were prevalent
2. Land clearing - flies rest on tree trunks
3. Wild animal slaughter
4. Pesticides - pour on solutions for cattle and DTT spray
5. Trapping
6. Release of sterile males - irradiated
7. Tied to poverty, health and politics
  1. Long-term sustainable options rarely found

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Human African Trypanosomiasis (HAT)

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	Created by maisie_oj about 11 years ago