An evaluation of benznidazole as a Chagas disease therapeutic

ABSTRACT

Introduction: As benznidazole is the first-line treatment for patients with Chagas disease, rational chemotherapy strategies are required based on the critical analysis of the evidence on the relevance and applicability of this drug at different disease stages.

Areas covered: The authors discuss the current understanding of benznidazole-based chemotherapy for Chagas disease, focusing specifically on epidemiology, pharmacokinetics, mechanism of action, clinical recommendations, cure criteria, and therapeutic efficacy in different phases of the disease.

Expert opinion: Benznidazole shows high bioavailability after oral administration. Benznidazole at 5–8 mg/kg/day and 5–10 mg/kg/day for 30–60 days are consistent clinical recommendations for children and adults, respectively. A high correlation between negative parasitological, serological, and polymerase chain reaction (PCR) assays in long-term post-therapeutic follow-up has been consistently used to evaluate therapeutic efficacy. These methods support the evidence that the success of benznidazole-based chemotherapy is closely correlated with the phase of infection in which the treatment is administered. The greater therapeutic efficacy is obtained in acute infections, gradually worsening as the infection becomes chronic. When therapeutic failure is confirmed by any diagnostic assay, benznidazole treatment does not always ensure better long-term prognosis, and Chagas cardiomyopathy may develop as well as in untreated patients.

KEYWORDS:

• American trypanosomiasis
• antiparasitic chemotherapy
• etiological therapy
• nitroimidazole
• therapeutic efficacy

Article Highlights

• After 40 years of clinical use, benznidazole-based chemotherapy remains as the first-line treatment for patients with Chagas disease.

• Pharmacokinetic data indicates that benznidazole shows high bioavailability after oral administration in children and adults infected with Trypanosoma cruzi.

• The current evidence indicates that benznidazole at 5-8 mg/kg/day and 5-10 mg/kg/day for 30-60 days are consistent clinical recommendations for children and adults with Chagas disease, respectively.

• Following treatment with benznidazole, parasitological cure has often been linked to negation of parasitemia, serology and parasite load. Thus, a high correlation between negative parasitological, serological, and polymerase chain reaction (PCR) assays in long-term post-therapeutic follow-up has been consistently used as markers of therapeutic efficacy.

• The current data of parasitological cure support the evidence that the success of benznidazole chemotherapy is closely correlated with the phase of infection in which the treatment is administered. Thus, a greater therapeutic efficacy is mainly obtained in acute infections, gradually worsening as the infection becomes chronic.

• When therapeutic failure is confirmed by any diagnostic method, benznidazole chemotherapy does not always ensure better long-term prognosis in patients with Chagas cardiomyopathy, and heart morphofunctional deterioration may progress as well as in untreated patients.

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Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This work was supported by the Brazilian agencies: the Fundação do Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG, processes APQ-01895-16 and PPM-00077-18) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, processes 303972/2017-3 and 423594/2018-4). This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (CAPES) – Finance Code 001.