Low-dose of benznidazole promotes therapeutic cure in experimental chronic Chagas' disease with absence of parasitism in blood, heart and colon

Exp Parasitol. 2020 Mar:210:107834. doi: 10.1016/j.exppara.2020.107834. Epub 2020 Jan 21.

Abstract

Studies suggest that the dose of the standard benznidazole (BNZ) treatment regimen might be too high. We investigated the efficacy of BNZ 20 and 40 mg/kg/day compared with standard dose (100 mg/kg/day) to induce cure in mice infected with Trypanosoma cruzi Y strain in the acute and chronic phases of Chagas' disease. Our findings indicate that an experimental treatment with a BNZ low-dose (40 mg/kg/day) is similarly effective as the usual dose in the chronic mice model (100% of cure). In addition, the treatment in the chronic model of Chagas' disease presented better results than the acute model and colon appears to be a key tissue when it comes to evaluating treatment efficacy compared to blood and heart. Therefore, our data suggest the reconsideration of the current therapy, mainly in the chronic phase of the disease.

Keywords: Benznidazole; Chagas disease; Low-dose; Treatment; Trypanosoma cruzi.

MeSH terms

  • Acute Disease
  • Animals
  • Blood / parasitology
  • Chagas Disease / drug therapy*
  • Chagas Disease / parasitology
  • Chronic Disease
  • Colon / parasitology
  • Cyclophosphamide / administration & dosage
  • Cyclophosphamide / pharmacology
  • Cyclophosphamide / therapeutic use
  • Female
  • Heart / parasitology
  • Immunosuppression Therapy
  • Mice
  • Neglected Diseases / drug therapy
  • Neglected Diseases / parasitology
  • Nitroimidazoles / administration & dosage*
  • Nitroimidazoles / therapeutic use
  • Real-Time Polymerase Chain Reaction
  • Trypanocidal Agents / administration & dosage*
  • Trypanocidal Agents / therapeutic use
  • Trypanosoma cruzi / drug effects
  • Trypanosoma cruzi / genetics
  • Trypanosoma cruzi / physiology

Substances

  • Nitroimidazoles
  • Trypanocidal Agents
  • Cyclophosphamide
  • benzonidazole