Benznidazole/miltefosine combination improves the treatment of chagas disease

Abstract

Chagas disease, caused by Trypanosoma cruzi, is one of the most prevalent parasitic diseases in Latin America. Currently, the available treatments, benznidazole and nifurtimox, have high toxicity, low solubility and reduced efficacy. This study investigates the effectiveness of combining miltefosine with benznidazole as a strategy to improve existing treatments. The research was conducted with 78 Swiss mice infected with 5000 trypomastigotes of T. cruzi (strain Y). The animals were divided into groups and treated with doses of 40mg/kg of miltefosine, administered orally for 10 consecutive or alternate days, and doses of 50 or 100mg/kg of benznidazole, administered for 20 consecutive days. Infected and uninfected control groups were included. After 150 days, the animals were sacrificed for analysis of parasitological cure. The combination of miltefosine and benznidazole demonstrated superior efficacy compared to isolated treatments. Alternating administration of 40mg/kg miltefosine with 50mg/kg benznidazole resulted in 62.5% cure, comparable to treatment with 100mg/kg benznidazole alone. The combination of 40 mg/kg of miltefosine with 100 mg/kg of benznidazole increased the cure rate to 87.5% (consecutive) and 100% (alternating). qPCR indicated a significant reduction in parasite DNA in cardiac and colonic tissues in the groups treated with the combinations. The results confirm that the combination of miltefosine with benznidazole enhances the effectiveness of the treatment, especially when miltefosine is administered every other day. This strategy can reduce the dose of benznidazole required, reducing toxicity and improving treatment adherence. Thus, the combination of drugs represents a promising approach to improving Chagas disease therapy, worthy of additional clinical investigation.