Etiology and Causative Agents of Sleeping Sickness
African trypanosomiasis is transmitted by flagellated protozoa of the genus Trypanosoma. The disease manifests in different forms depending on the species:
- Trypanosoma rhodesiense causes the East African form;
- Trypanosoma gambiense causes the West African form.
Note that American trypanosomiasis (Chagas disease) also exists, caused by T. cruzi.
Drugs for Early-Stage Disease
In the early stages of infection, before central nervous system (CNS) involvement, the following agents are used:
- Suramin: Used in the early stages of sleeping sickness. Its mechanism of action involves binding to macromolecules, inhibiting energy metabolism enzymes (such as glycerol-phosphate dehydrogenase), and blocking RNA polymerase, which disrupts parasite replication. Adverse effects include pruritus, paresthesias, and dyspepsia.
- Pentamidine: Effective in early-stage disease caused by T. gambiense and certain strains of T. rhodesiense. It selectively targets kinetoplast DNA in protozoa, disrupting nucleic acid and protein synthesis. Potential adverse reactions include hypotension, fatigue, pancreatitis, and renal impairment.
Therapy for Late-Stage CNS Involvement
Once the infection crosses the blood-brain barrier and involves the central nervous system, standard early-stage drugs become ineffective. Potent agents are required at this stage:
- Melarsoprol: An organic arsenical compound complexed with dimercaprol. Because trypanosomes lack the Krebs cycle and synthesize ATP exclusively via glycolysis, the drug inhibits the parasite's pyruvate kinase, leading to parasite death. It is a highly toxic agent (with a mortality rate of 4–6%) capable of causing severe phlebitis and reactive encephalopathy. Corticosteroids are co-administered to reduce the risk of reactive encephalopathy.
- Eflornithine: A less toxic alternative to melarsoprol. It demonstrates high efficacy against the West African strain T. gambiense in both early and late stages, but is completely ineffective against the East African form.