Development of a New Chemotherapy for Human African Trypanosomiasis by Using an Animal Model: Suramin with DL-Alpha-Difluoromethylornithine.

摘要

Eighteen isolates of Trypanosoma brucei rhodesiense were acquired and several were selected for a preclinical evaluation of a combination of eflornithine and suramin as a treatment for African Sleeping Sickness. The sensitivity to eflornithine, suramin arsenicals and diamidines of seventeen isolates was measured in acute, non-central nervous system (CNS), disease models. The discovery of a wide variation in sensitivity of these mostly wild isolates to standard and experimental drugs has important implications for any preclinical evaluation of any anti-trypanosomal drug candidates. Seven isolates were evaluated for suitability as a CNS model; one was chosen for evaluation of the combination suramin and eflornithine as therapy for CNS disease. The combination was effective despite the fact that these two agents used singly were ineffective. In two acute infection models the combination produced cures at doses much lower than that required when the drugs were used singly. No adverse interactions were found even when high doses of suramin and eflornithine were combined.