Etiology and pathogens of sleeping sickness
African trypanosomiasis is transmitted by flagellated protozoa of the genus Trypanosoma. The disease occurs in different forms depending on the pathogen:
- Trypanosoma rhodesiense causes the East African form;
- Trypanosoma gambiense causes the West African form.
It is important to note that there is also American trypanosomiasis (Chagas disease), which is caused by T. cruzi.
Drugs for early stages of the disease
In the early stages of infection, before central nervous system involvement, the following agents are used:
- Suramin (Suramin): Used in the initial stages of sleeping sickness. Its mechanism of action involves binding to macromolecules, inhibiting energy metabolism enzymes (e.g., glycerol-3-phosphate dehydrogenase), and blocking RNA polymerase, which disrupts parasite replication. Side effects include pruritus, paresthesia, and dyspepsia.
- Pentamidine: Effective in the early stages 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.
Late-stage therapy for CNS involvement
When the infection invades the central nervous system, standard early-stage agents become ineffective. In this case, potent drugs are used:
- Melarsoprol: A chemical complex of an arsenic derivative and dimercaprol. Since trypanosomes lack the Krebs cycle and synthesize ATP exclusively via glycolysis, the drug inhibits the parasite's pyruvate kinase, causing pathogen death. This is a highly toxic agent (fatality rate of 4–6%) capable of causing severe phlebitis and reactive encephalopathy. To reduce the risk of the latter, corticosteroids are additionally prescribed.
- 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.
Briefly: answers to topical questions
What side effects are characteristic of suramin?
Suramin is characterized by a number of adverse reactions, including skin manifestations, neurological disorders, and gastrointestinal issues. The following side effects may occur during therapy with this drug:
- Pruritus — a skin reaction associated with the use of the drug.
- Paresthesia — specific neurological symptoms.
- Dyspeptic disorders — digestive disturbances, including nausea and vomiting.
What drugs are used to treat American trypanosomiasis (Chagas disease)?
Specific antiparasitic agents, as well as antiarrhythmic drugs for cardiac complications, are used to treat American trypanosomiasis. Specific therapy is effective only in the acute phase of the disease and includes the following medications:
- Benznidazole — used to treat acute-stage infection.
- Nifurtimox — used alongside benznidazole.
When chronic cardiomyopathy with ventricular rhythm disturbances develops, pharmacotherapy is prescribed:
- Amiodarone — indicated to reduce episodes of arrhythmia in the presence of symptomatic ventricular extrasystoles or tachycardia.
Suramin and Pentamidine for the early stage (pre-CNS), Melarsoprol (arsenic) for the late stage (with CNS), and Eflornithine as a safe analogue against T. gambiense.
Class and exam questions
Which drug is the choice for treating the late stage of African trypanosomiasis with CNS involvement?
The drug of choice for late stages is melarsoprol, which contains an arsenic compound. It disrupts parasite glycolysis by inhibiting pyruvate kinase.
Which medications are used to reduce the risk of reactive encephalopathy during melarsoprol therapy?
Corticosteroids are used to prevent and reduce the risk of reactive encephalopathy.
Is eflornithine effective in the East African form of trypanosomiasis?
No, eflornithine is ineffective against the East African form caused by T. rhodesiense. It is highly effective only against the West African form of T. gambiense.
What else to study on this topic
- Biochemical features of trypanosome metabolism and the absence of the Krebs cycle
- Comparative characteristics of the mechanisms of action of suramin and pentamidine
- Prevention and treatment of complications associated with melarsoprol use
- Differences between the West African and East African forms of sleeping sickness
- Specifics of eflornithine use in T. gambiense
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