Experimental and Clinical Treatment of Chagas Disease: A Review

Abstract

Abstract.Chagas disease (CD) is caused by the protozoan parasite Trypanosoma cruzi that infects a broad range of triatomines and mammalian species, including man. It afflicts 8 million people in Latin America, and its incidence is increasing in nonendemic countries owing to rising international immigration and nonvectorial transmission routes such as blood donation. Since the 1960s, the only drugs available for the clinical treatment of this infection have been benznidazole (BZ) and nifurtimox (NFX). Treatment with these trypanocidal drugs is recommended in both the acute and chronic phases of CD. These drugs have low cure rates mainly during the chronic phase, in addition both drugs present side effects that may result in the interruption of the treatment. Thus, more efficient and better-tolerated new drugs or pharmaceutical formulations containing BZ or NFX are urgently needed. Here, we review the drugs currently used for CD chemotherapy, ongoing clinical assays, and most-promising new experimental drugs. In addition, the mechanism of action of the commercially available drugs, NFX and BZ, the biodistribution of the latter, and the potential for novel formulations of BZ based on nanotechnology are discussed. Taken together, the literature emphasizes the urgent need for new therapies for acute and chronic CD.

Efficacy and safety assessment of different dosage of benznidazol for the treatment of Chagas disease in chronic phase in adults (MULTIBENZ study): study protocol for a multicenter randomized Phase II superiority clinical trial

“…CD continues to be an infectious disease with one of the highest disease burdens worldwide. Despite the modest cure rates in adult chronic patients and its safety profile, BNZ remains the best treatment option against the disease due to the lack of therapeutic alternatives [7]. Conventional diagnostic methods for establishing cure rates in chronic CD have marked inherent limitations; however, the use of more sensitive methods for parasite detection, such as PCR, could provide a suitable tool for follow-up assessment of treatment in patients with CD, because detectable T. cruzi DNA in peripheral blood samples after treatment end is considered a therapeutic failure [31].…”

“…However, current schemes of this treatment have some limitations. On the one hand, it has a limited efficacy based on seroconversion (around 50-80% in the acute phase of the disease and 8-20% in the chronic phase) [7]. Another important limitation is the high rate of adverse events (AEs) when using these drugs.…”

Design, synthesis, molecular modelling, and in vitro evaluation of tricyclic coumarins against Trypanosoma cruzi

“…The infection can lead to death due to cardiac arrhythmias or progressive heart failure caused by the destruction of the heart muscle and nervous system (Argolo et al, 2008;Coura & Castro, 2002). Both NFX and BZ cause undesirable side-effects and present low cure rates mainly in the chronic phase of disease (Junior et al, 2017). Both NFX and BZ cause undesirable side-effects and present low cure rates mainly in the chronic phase of disease (Junior et al, 2017).…”

“…Currently, only two medicines are approved for the treatment of Chagas disease: nifurtimox (NFX) or benznidazole (BZ), both of which were released for sale in the early 1970s (Oliveira et al, 2008). Although BZ and NFX drugs can reach a 76% cure rate in acute cases of Chagas disease, their efficiency is dramatically lower in chronic infections where the percentage of cure is around 8% (Junior et al, 2017;Oliveira et al, 2008). Although BZ and NFX drugs can reach a 76% cure rate in acute cases of Chagas disease, their efficiency is dramatically lower in chronic infections where the percentage of cure is around 8% (Junior et al, 2017;Oliveira et al, 2008).…”

“…Both NFX and BZ cause undesirable side-effects and present low cure rates mainly in the chronic phase of disease (Junior et al, 2017). Although BZ and NFX drugs can reach a 76% cure rate in acute cases of Chagas disease, their efficiency is dramatically lower in chronic infections where the percentage of cure is around 8% (Junior et al, 2017;Oliveira et al, 2008).…”