African Trypanosomiasis

Aka: African Trypanosomiasis, African Sleeping Sickness, Trypanosoma Brucei Rhodesiense, Trypanosoma Rhodesiense, Trypanosoma Brucei Gambiense, Trypanosoma Gambiense

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II. Pathophysiology

  1. African Trypanosomiasis (African Sleeping Sickness)
    1. Disease affecting both humans and animals in Central Africa where it is endemic
  2. Caused by 2 Trypanosoma species
    1. T. gambiense (West African Sleeping Sickness)
      1. Slowly progressive fevers and wasting
      2. Late neurologic findings
    2. T. rhodesiense (East African Sleeping Sickness)
      1. More severe than T. gambiense (West African)
      2. Rapid progression from fever to neurologic symptoms to death within weeks to months
      3. Most disease in travelers occurs in Tanzania, Malawi or Zambia
  3. Infection
    1. Transmitted by the bite of a blood-sucking Tsetse Fly
      1. Firm, red, painful Skin Ulcer forms at bite site and then heals within 2 weeks
    2. Trypomastigote spreads within the human bloodstream
      1. Trypomastigote is the motile, flagellated form of Trypanosoma
      2. Trypomastigote targets Lymph Nodes and the Central Nervous System
  4. Variable Surface Glycoproteins (VSG) and undulating fever
    1. Trypanosomes are coated with millions of copies of a single Glycoprotein variety (VSG)
      1. Trypanosomes have genetic code to generate thousands of different VSGs
      2. However, each trypanosome surface contains only 1 VSG type at a time
    2. Antibody formation to a VSG triggers a strong immune response with fever
      1. Targeted trypanosomes generate offspring with a new VSG, not yet recognized by the host
      2. Ultimately Antibody is generated in 2-3 weeks, triggering an immune response and fever recurrence

III. Findings

  1. Acute Infection
    1. Initial skin lesion at bite site (Week 0-2 after Tsetse bite)
      1. Firm, red, painful Skin Ulcer forms at bite site and then heals within 2 weeks
    2. Initial systemic symptoms (Week 2-3 after Tsetse bite)
      1. Fever
      2. Headache
      3. Dizziness
      4. Lymphadenopathy
  2. Stage 1: Hemolymphatic Stage (Undulating fever months after Tsetse bite)
    1. Fever-free periods alternating with episodes of fever
  3. Stage 2: Meningoencephalitic Stage (progressive neurologic findings)
    1. Daytime Somnolence
    2. Behavior changes
    3. Progressive deficits in speech and walking
    4. Progression to coma and death

IV. Diagnosis

  1. Microscopy
    1. Trypomastigotes may be seen in peripheral blood, lymph biopsy or spinal fluid
  2. Serology
    1. Only available for T. gambiense

V. Management: West African Trypanosomiasis (T. gambiense)

  1. General
    1. Inpatient Antibiotic course despite oral administration
    2. Monitor for relapse with reevaluation (history and exam) every 6 months for 24 months
  2. Fexindazole
    1. Indications
      1. Age >=6 years AND body weight >20kg AND CSF Leukocytes <100 wbc/uL
    2. Contraindications
      1. First trimester pregnancy (may use in second or third trimester)
      2. Unknown CSF Leukocyte count OR CSF Leukocytes >100 wbc/uL
    3. Dosing weight >=35 kg
      1. Load: 1800 mg (3 tablets) once daily for 4 days
      2. Next: 1200 mg (2 tablets) once daily for 6 days
    4. Dosing weight 20 kg to 35 kg
      1. Load: 1200 mg (2 tablets) once daily for 4 days
      2. Next: 600 mg (1 tablet) once daily for 6 days
  3. NECT (Eflornithine/Nifurtimox)
    1. Indications
      1. Severe Stage 2 Trypanosomiasis with CSF Leukocytes >100 wbc/uL (any age)
    2. Dosing
      1. Eflornithine 400 mg/kg/day IV divided every 12 hours for 7 days AND
      2. Nifurtimox 15 mg/kg/day divided every 8 hours for 10 days
  4. Pentamidine
    1. Indications
      1. Stage 1 AND (Age <6 years OR body weight <20kg) OR
      2. Alternative regimen for age>=6 years and non-severe Stage 1-2 with CSF Leukocytes <100 wbc/uL
    2. Contraindications (use NECT instead)
      1. Stage 2 Trypanosomiasis AND (Age <6 years OR body weight <20kg)
    3. Dosing
      1. Pentamidine 4 mg/kg IV for 7 days

VI. Management: East African Trypanosomiasis (T. rhodesiense)

  1. Fexindazole
    1. Indications
      1. Age >=6 years AND body weight >20kg (Stage 1 or 2)
    2. Contraindications
      1. Unknown CSF Leukocyte count OR CSF Leukocytes >100 wbc/uL
      2. First trimester pregnancy (may use in second or third trimester)
        1. Relative contraindication due to rapid lethality of East African Trypanosomiasis
        2. Start with either Fexindazole or Pentamidine in pregnancy regardless of trimester
    3. Dosing weight >=35 kg
      1. Load: 1800 mg (3 tablets) once daily for 4 days
      2. Next: 1200 mg (2 tablets) once daily for 6 days
    4. Dosing weight 20 kg to 35 kg
      1. Load: 1200 mg (2 tablets) once daily for 4 days
      2. Next: 600 mg (1 tablet) once daily for 6 days
  2. Suramin
    1. Indications
      1. Stage 1 AND (Age <6 years OR body weight >20kg)
    2. Dosing
      1. First Test Dose: 5 mg/kg IV
      2. Next: 20 mg/kg (up to 1 g) on days 1, 3, 7, 14 and 21
  3. Melarsoprol
    1. Indications
      1. Stage 2 AND (Age <6 years OR body weight >20kg)
    2. Dosing
      1. Melarsoprol 2.2 mg/kg/day IV for 10 days
      2. Consider Corticosteroid pretreatment to prevent encephalopathy
      3. Consider pretreatment with Suramin to treat blood stages before Melarsoprol

VII. Resources

  1. African Trypanosomiasis (WHO)
    1. https://www.who.int/news-room/fact-sheets/detail/trypanosomiasis-human-african-(sleeping-sickness)
  2. African Trypanosomiasis (Stat Pearls)
    1. https://www.ncbi.nlm.nih.gov/books/NBK535413/

VIII. References

  1. Gladwin, Trattler and Mahan (2014) Clinical Microbiology, Medmaster, Fl, p. 349
  2. (2025) Sanford Guide, accessed 7/11/2025 on IOS
  3. Ortiz-Martínez (2023) Curr Trop Med Rep 10(4):222-34 +PMID: 38939748 [PubMed]

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