What is the treatment protocol for trypanosomiasis (Trypanosoma infection)?

Treatment Protocol for Trypanosomiasis

For African trypanosomiasis (sleeping sickness), fexinidazole is now the first-line treatment for both early and late-stage disease in patients aged 6 years and older with bodyweight ≥20 kg. 1

Types of Trypanosomiasis

African Trypanosomiasis

African trypanosomiasis (sleeping sickness) is caused by two subspecies:

1. Trypanosoma brucei gambiense (West African)

   • Chronic course with late CNS disease developing in months to years
   • Symptoms: irritability, personality changes, inability to concentrate, sleep disturbances, severe headache, ataxia, extrapyramidal signs
   • Diagnosis: Giemsa staining of chancre and lymph nodes, serologic testing, card agglutination test (sensitivity 96%)

2. Trypanosoma brucei rhodesiense (East African)

   • More acute course leading to death within weeks to months
   • Symptoms: sleep disturbances, refractory headaches, progressive neurologic impairment
   • Diagnosis: CSF smears, CSF IgM, inoculation of specimens into mice or rats

American Trypanosomiasis (Chagas Disease)

Caused by Trypanosoma cruzi with acute, latent, and chronic phases.

Treatment Protocols

African Trypanosomiasis

First-Line Treatment

• Fexinidazole: 10-day treatment course for both early and late-stage disease 1
  • Must be administered with food during or immediately after the main meal
  • Direct observation required due to risk of non-compliance and side effects
  • For patients ≥6 years and ≥20 kg

Alternative Treatments

1. T.b. gambiense (West African):

   • Early stage: Pentamidine
   • Late stage: Eflornithine (A-II) 2
   • Alternative for late stage: Melarsoprol (A-II) 2

2. T.b. rhodesiense (East African):

   • Early stage: Suramin
   • Late stage: Melarsoprol (A-II) 2

Special Considerations

• Lumbar puncture can be avoided in patients eligible for fexinidazole
• Rapid treatment initiation is crucial for rhodesiense HAT due to its rapid progression
• Close monitoring required at end of treatment and at 1,3,6, and 12 months
• Compassionate use of fexinidazole may be considered in children <6 years or <20 kg when other options have failed

American Trypanosomiasis (Chagas Disease)

Diagnosis

• Acute phase (4-8 weeks): Microscopy of Giemsa-stained thick and thin blood or buffy coat films 2
• Chronic phase: Serological testing

Treatment

• Nifurtimox: FDA-approved for pediatric patients (birth to <18 years, weighing ≥2.5 kg) 3
• Benznidazole: Alternative treatment (not mentioned in evidence but standard of care)

Disease Staging

African Trypanosomiasis

• Early stage (hemolymphatic): Parasites in blood and lymph
• Late stage (encephalitic): Parasites cross blood-brain barrier into CNS
• Staging traditionally done via lumbar puncture and CSF analysis

Important Considerations

• Treatment must begin promptly, especially for T.b. rhodesiense which progresses rapidly
• Monitor for adverse effects, particularly with melarsoprol which has 5% mortality due to post-treatment reactive encephalopathy
• Ensure complete treatment course to prevent relapse
• Follow-up is essential to detect treatment failure or relapse

Future Directions

• Acoziborole: Single-dose oral treatment for gambiense HAT expected to be available soon 4
• Nifurtimox-eflornithine combination therapy (NECT) is being increasingly used for late-stage gambiense HAT 5

The treatment landscape for trypanosomiasis has improved significantly with the introduction of fexinidazole, which has simplified treatment by being effective for both stages of disease and reducing the need for toxic drugs like melarsoprol.