Response to different benznidazole doses in animal models of chronic phase Chagas disease: a critical review

Abstract

Chagas disease is a protozoan infection that was identified over a century ago. No drugs are available to treat the indeterminate and determinate chronic phases of the disease. Success of a drug design is dependent on correct biological evaluation. Concerning new drug designs for Chagas disease, it is essential to first identify the most effective, existing, experimental chronic protocols that can be used for comparison purposes. Here, we present a literature review regarding experimental models with chronic Chagas disease to evaluate the efficacy of benznidazole (BZN). We searched literature published in PubMed and Web of Science databases, using these keywords: animal model, BZN, Chagas disease, T. cruzi, and chronic phase, with no timeframe limitations. We excluded articles involving acute phase animal models and/or those without BZN treatment. The selected studies were conducted using different BZN concentrations (10mg-100mg) involving several different periods (5-70 days). Concentrations and durations of use are directly related to side effects, but do not prevent chronic tissue lesions. BZN use during the late/chronic phases of Chagas disease is unable to eliminate amastigote forms present in infected tissues. This study suggests the administration of a lower BZN concentration (<100mg/kg/day) during the chronic phase of the animal model, as this had been reported to result in fewer side effects.

Hydroxymethylnitrofurazone treatment in indeterminate form of chronic Chagas disease: Reduced intensity of tissue parasitism and inflammation—A histopathological study

“…We used a dose of 60 mg/kg/d for the BZN group and 150 mg/kg/d for the NFOH group, following a previous report from Davies et al, to guarantee the maximal number of surviving animals up until the end of the procedure, after the immunosuppression stage . In animal models, the BZN concentration in the chronic phase of Chagas disease, is directly related to side effects; this is favourable to use lower concentration in order to increase the period of treatment …”

“…22,24 In animal models, the BZN concentration in the chronic phase of Chagas disease, is directly related to side effects; this is favourable to use lower concentration in order to increase the period of treatment. 70 The treatment started after 7 weeks of infection during the period of subacute parasitaemia. The period of drug treatment was performed according to previous procedures described in the literature.…”

Current Challenges and Obstacles to Drug Development for Chagas Disease

“…The optimal experimental protocol is the one that best relates to human response. The data reported in the mini-review published by Scarim and co-workers [27] suggest that for experimental protocol in animals chronically infected with Chagas disease, a treatment with lower doses of benznidazole is more advantageous and can be used as a base to compare new drugs with BZN in the chronic phase of Chagas disease.…”

Determinação da atividade biológica de bioterápico \'in vivo\' na infecção experimental determinada por Trypanosoma cruzi

“…A dificuldade em se estabelecer uma posologia adequada para o tratamento da DC, principalmente na FC, não é restrita a estudo com animais ou protocolos homeopáticos. Diversas doses e posologias já foram conduzidas em estudos clínicos com doentes na fase crônica da doença (SCARIM et al, 2018). Os esquemas de tratamento apresentam concentrações de benzonidazol de 10 a 100mg, em períodos de 5 a 70 dias.…”