Antitrypanosomal

Antitrypanosomal refers to drugs that act against Trypanosoma parasites, notably Trypanosoma brucei, which causes African trypanosomiasis (sleeping sickness), and Trypanosoma cruzi, which causes American trypanosomiasis (Chagas disease). These drugs are used in humans and, in many cases, in veterinary medicine. Treatments are stage- and subspecies-specific and require careful clinical decision-making.

In African trypanosomiasis, therapy depends on the subspecies and disease stage. Early, blood-borne infections (T. b. gambiense or T. b. rhodesiense) may be treated with suramin (often for T. b. rhodesiense) or pentamidine (for T. b. gambiense). Late-stage disease with central nervous system involvement requires drugs that cross the blood–brain barrier. Eflornithine, sometimes in combination with nifurtimox (NECT), is used for T. b. gambiense, while melarsoprol is reserved for cases where other treatments are not effective or available due to its significant toxicity.

For American trypanosomiasis, the main antitrypanosomal agents are nifurtimox and benznidazole. These drugs are most effective during acute infection and are used with varying success in chronic cases. Treatment choices consider age, clinical status, and potential adverse effects, such as dermatitis, neuropathy, and gastrointestinal symptoms.

Mechanisms of action differ among agents: eflornithine inhibits polyamine synthesis, while nifurtimox and benznidazole generate reactive oxygen species to damage parasite components. Suramin and pentamidine disrupt parasite metabolism but are not effective against CNS stages. Safety concerns include severe toxicity with arsenical melarsoprol, which limits its use, and a range of tolerability issues with other drugs.

Overall, antitrypanosomal therapy requires species- and stage-appropriate regimens, with ongoing challenges in toxicity management, drug resistance, and access in endemic regions.