What is the treatment for African trypanosomiasis?

Treatment for African Trypanosomiasis

Fexinidazole is now the first-line treatment for African trypanosomiasis in patients aged 6 years and older with bodyweight ≥20 kg, replacing traditional treatments like suramin and melarsoprol. 1

Disease Overview

African trypanosomiasis (sleeping sickness) comes in two forms:

• Trypanosoma brucei gambiense (West African) - chronic disease progressing over months to years
• Trypanosoma brucei rhodesiense (East African) - acute disease progressing rapidly over weeks to months

The disease has two stages:

1. Early (hemolymphatic) stage - parasites in blood and lymphatic system
2. Late (encephalitic) stage - parasites cross the blood-brain barrier to invade the CNS

Treatment Algorithm Based on Disease Type and Patient Characteristics

For T.b. rhodesiense (East African):

Patients ≥6 years with bodyweight ≥20 kg:

• First-line: Fexinidazole - oral treatment for both early and late-stage disease 1
  • Must be administered with food during or immediately after main meal
  • Requires 10-day treatment course with direct observation by trained staff
  • Follow-up evaluations at end of treatment, 1,3,6, and 12 months

Patients <6 years or bodyweight <20 kg:

• Early stage: Suramin 1
• Late stage: Melarsoprol 1
  • Requires lumbar puncture for disease staging

When recommended drugs not readily available:

• Immediate interim treatment with pentamidine if available 1
• Switch to recommended treatment as soon as it becomes available

For T.b. gambiense (West African):

Patients ≥6 years with bodyweight ≥20 kg:

• First-line for both stages: Fexinidazole 1
• Alternative for late-stage: Eflornithine (intravenous) 1, 2
  • Often combined with nifurtimox for improved efficacy 3

Patients <6 years or bodyweight <20 kg:

• Early stage: Pentamidine
• Late stage: Eflornithine 1, 2

Important Clinical Considerations

Fexinidazole Administration

• Must be given with food - bioavailability substantially reduced without food 1
• Direct observation required - trained health staff must observe each dose due to:
  • 10-day treatment duration
  • Risk of non-compliance
  • Common side effects (nausea, vomiting)
  • Need for concomitant food intake 1

Monitoring and Follow-up

• Close monitoring required due to limited data on fexinidazole in rhodesiense HAT 1
• Clinical evaluation at end of treatment and at 1,3,6, and 12 months 1
• If relapse suspected, examine bodily fluids including CSF for trypanosomes or CSF leukocytosis

Side Effects to Monitor

• Fexinidazole: Vomiting (38%), nausea (33%), QT prolongation, neutropenia, neuropsychiatric reactions 1
• Melarsoprol: Highly toxic with post-treatment reactive encephalopathy in up to 10% of patients, with 50% mortality among those affected (5% overall mortality) 4, 3, 5
• Eflornithine: Hair loss, facial swelling, seizures, hearing impairment, gastrointestinal disturbances, headache, weakness, dizziness, and hematological toxicities 2

Disease Staging

• Lumbar puncture remains necessary for disease staging in patients who cannot receive fexinidazole 1
• CSF analysis is used to determine if CNS is involved
• Lumbar puncture can be avoided in patients eligible for fexinidazole, as it is effective for both stages 1

Cautions and Pitfalls

• Do not administer fexinidazole without food - active metabolites may not reach therapeutic levels 1
• Consider alternatives if oral absorption uncertain - in critically ill patients or those unable to swallow, use suramin or melarsoprol based on disease stage 1
• Ensure compliance with full 10-day course of fexinidazole to prevent treatment failure 1
• Rapid treatment initiation is crucial for rhodesiense HAT due to its rapid progression 1
• Compassionate use of fexinidazole may be considered in children <6 years or <20 kg when other options have failed, but requires specialist consultation 1