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Updated: Nov 26, 2025
In Vitro Drug Screening Against All Life Cycle Stages of Trypanosoma cruzi Using Parasites Expressing β-galactosidase
Published on: November 5, 2021
Trypanocidal drugs for late-stage, symptomatic Chagas disease (Trypanosoma cruzi infection)
Maite Vallejo1, Pedro Pa Reyes1, Mireya Martinez Garcia2
1Instituto Nacional de Cardiología Ignacio Chávez, Juan Badiano No. 1. Col. Seccion XVI, Tlalpan, Mexico.
Insights
This review found insufficient evidence to support the use of benznidazole or nifurtimox for treating late-stage Chagas disease (Chagasic cardiomyopathy). While benznidazole may reduce antibody titers, it increases adverse events without clear cardiac benefits.
Area of Science:
- Cardiology
- Infectious Diseases
- Pharmacology
Background:
- Chagas disease can cause progressive, lethal heart conditions.
- Current antiparasitic drugs have limited efficacy and are used early.
- Treatment of chronic chagasic cardiomyopathy (CCC) with these drugs is being explored.
Purpose of the Study:
- To evaluate the benefits and harms of nitrofurans and trypanocidal drugs for treating late-stage Chagas disease and CCC.
- Assess outcomes including parasite reduction, mortality, adverse effects, and quality of life.
Main Methods:
- Searched multiple databases (Cochrane, MEDLINE, Embase, LILACS) and clinical trial registries.
- Included randomized controlled trials (RCTs) comparing trypanocidal drugs to placebo for late-stage Chagas disease and CCC.
- Two independent reviewers assessed data and risk of bias.
Main Results:
- Two RCTs were included, involving benznidazole and nifurtimox versus placebo.
- Benznidazole showed potential benefit in reducing antibody titers but increased adverse events (rash, GI symptoms, neuropathy).
- Evidence for benznidazole's effect on parasitemia, heart failure, and ventricular tachycardia was uncertain or low quality. Nifurtimox data were very limited.
Conclusions:
- Insufficient evidence exists to confirm the efficacy of benznidazole and nifurtimox for treating late-stage Chagas disease and CCC.
- Further research is needed to establish the role of these drugs in managing chronic Chagasic cardiomyopathy.
Background:
People with Chagas disease may develop progressive and lethal heart conditions. Drugs to eliminate the parasite Trypanosoma cruzi (T cruzi) currently carry limited therapeutic value and are used in the early stages of the disease. Extending the use of these drugs to treat chronic chagasic cardiomyopathy (CCC) has also been proposed.
Objectives:
To assess the benefits and harms of nitrofurans and trypanocidal drugs for treating late-stage, symptomatic Chagas disease and CCC in terms of blood parasite reduction or clearance, mortality, adverse effects, and quality of life.
Search Methods:
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and LILACS databases on 12 November 2019. We also searched two clinical trials registers, ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), on 3 December 2019.
Selection Criteria:
We included randomised controlled trials (RCTs) assessing trypanocidal drugs versus placebo or no treatment for late-stage, symptomatic Chagas disease and CCC.
Data Collection And Analysis:
We conducted the reporting of the review according the standard Cochrane methods. Two review authors independently retrieved articles, performed data extraction, and assessed risk of bias. Any disagreements were resolved by a third review author. We contacted study authors for additional information.
Main Results:
We included two studies in this review update. One RCT randomly assigned 26 participants to benznidazole 5 mg/kg/day; 27 participants to nifurtimox 5 mg/kg/day; and 24 participants to placebo for 30 days. The second RCT, newly included in this update, randomised 1431 participants to benznidazole 300 mg/day for 40 to 80 days and 1423 participants to placebo. We also identified one ongoing study. Benznidazole compared to placebo At five-year follow-up, low quality of the evidence suggests that there may be a benefit of benznidazole when compared to placebo for clearance or reduction of antibody titres (risk ratio (RR) 1.25, 95% confidence interval (CI) 1.14 to 1.37; 1 trial; 1896 participants). We are uncertain about the effects of benznidazole for the clearance of parasitaemia demonstrated by negative xenodiagnosis, blood culture, and/or molecular assays due to very limited evidence. Low quality of the evidence suggests that when compared to placebo, benznidazole may make little to no difference in the risk of heart failure (RR 0.89, 95% CI 0.69 to 1.14; 1 trial; 2854 participants) and ventricular tachycardia (RR 0.80, 95% CI 0.51 to 1.26; 1 trial; 2854 participants). We found moderate quality of the evidence that adverse events increase with benznidazole when compared to placebo (RR 2.52, 95% CI 2.09 to 3.03; 1 trial; 2854 participants). Adverse effects were observed in 23.9% of patients in the benznidazole group compared to 9.5% in the placebo group. The most frequent adverse effects were: cutaneous rash, gastrointestinal symptoms, and peripheral polyneuropathy. No data were available for the outcomes of pathological demonstration of tissue parasites and quality of life. Nifurtimox compared to placebo Data were only available for this comparison for the outcome clearance or reduction of antibody titres, and we are uncertain about the effect due to very limited evidence. Regarding adverse events, one RCT mentioned in a general manner that nifurtimox caused intense adverse events, without any quantification.
Authors' Conclusions:
There is insufficient evidence to support the efficacy of the trypanocidal drugs benznidazole and nifurtimox for late-stage, symptomatic Chagas disease and CCC.
