Benznidazole for the treatment of Chagas disease

ABSTRACT

Introduction

Chagas disease affects 6–7 million people, mainly in the Americas, and benznidazole is one of the two therapeutic options available. Trypanocide treatment aims to eliminate the parasite from the body to prevent the establishment or progression of visceral damage, mainly cardiac and/or digestive. Remarkably, it helps interrupt vertical transmission when administered to women of childbearing age.

Areas covered

We discuss the basic and scarce data regarding chemical, pharmacokinetic, and pharmacodynamic structure. We also collect the most important data from previous phase II and III studies, as well as studies currently underway and upcoming. We reflect on the main indications for treatment and its challenges, such as the profile of adverse effects in adults, the pharmaceutical formulations, the search for reliable biomarkers, as well as regulatory aspects and access barriers. Alternative strategies such as shorter regimens, lower doses, and fixed doses are currently being evaluated to improve access and the safety profile of this treatment.

Expert opinion

Benznidazole is likely to continue to be the drug of choice for Chagas disease in the coming years. However, it would probably be with a different treatment scheme.

KEYWORDS:

• Chagas disease
• treatment
• benznidazole
• nitroimidazole
• efficacy
• adverse drug reactions

Article highlights

• Trypanocidal treatment is recommended in acute, congenital cases, reactivations, and in chronic cases under the age of 19 years old. It should also be considered in the chronic phase for patients between 19 and 50 years of age who do not have severe cardiological dysfunction, and be individually considered in those over 50 years balancing risks and potential benefits.

• Regardless of the clinical stage, women of childbearing age should be treated due to its relevance to interrupt transmission and the clear benefit for public health.

• BNZ is well tolerated by newborns and children, but most adult patients experience at least one ADR during their treatment course when exposed to it. ADRs are often mild to moderate but they might lead to treatment discontinuations, thus the major relevance of closely monitoring treatment period so as to best control adverse events and manage their impact.

• A deeper understanding of BNZ PK and PD profile could improve the efficacy of the treatment and contribute to the development of safer regimens.

• Research on biomarkers for the timely assessment of treatment efficacy is mandatory. Availability of such biomarkers will be fundamental both for the clinical evaluation of new drugs or new regimes with existing ones, as well as for the daily clinical management of patients under follow-up.

• Ongoing clinical trials aim to validate the use of alternative regimens and/or dosages of BNZ, in order to improve the safety and decrease the treatment costs.

• Endemic and non-endemic countries need to ensure access to treatment with BNZ.

Declaration of interest

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

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

Scientific accuracy review

Elea provided a scientific accuracy review at the request of the journal editor.

Additional information

Funding

This work was supported by the Instituto de Salud Carlos III RICET Network for Cooperative Research in Tropical Diseases [ISCIII - RD12/0018/0010; PI1290] and FEDER, and by the Departament d’Universitats i Recerca de la Generalitat de Catalunya, Spain [AGAUR; 2017SGR00924]. NCS pre-doctoral fellowship and CFB research are funded by Fundació La Marató de TV3 [reference 566/U/2018]. MJP research is supported by the Ministry of Health, Government of Catalunya [PERIS 2016-2010 SLT008/18/00132]. We acknowledge support from the Spanish Ministry of Science and Innovation through the ‘Centro de Excelencia Severo Ochoa 2019–2023’ Program (CEX2018-000806-S). ISGlobal and IGTP are members of the CERCA Program, Generalitat de Catalunya.