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Meta-Analysis
. 2022 May 16;16(5):e0010386.
doi: 10.1371/journal.pntd.0010386. eCollection 2022 May.

Use of benznidazole to treat chronic Chagas disease: An updated systematic review with a meta-analysis

Clara Crespillo-Andújar  1   2   3 , Belén Comeche  1 , Davidson H Hamer  4   5   6 , Ingrid Arevalo-Rodriguez  2   7   8 , Noelia Alvarez-Díaz  9 , Javier Zamora  2   7   8   10 , José A Pérez-Molina  1   2   3
Affiliations
Meta-Analysis

Use of benznidazole to treat chronic Chagas disease: An updated systematic review with a meta-analysis

Clara Crespillo-Andújar et al. PLoS Negl Trop Dis. .

Abstract

Background: Approximately 6 million people worldwide are affected by Chagas disease, with many in the chronic phase of the disease (CCD). It is crucial to evaluate the effectiveness of benznidazole for CCD treatment.

Methods/principal findings: We updated a meta-analysis published in 2009 up to February 2021, including controlled trials (RCT) and prospective observational studies (OBS) that compared benznidazole vs placebo/no-treatment (P/nT). Main outcomes evaluated were clinical progression (CP) and seroreversion with subgroup analysis performed according to study design and participants' age. Parasitological response and safety were also described. We identified 879 articles and selected nine for inclusion (corresponding to eight studies). After adding the nine articles from the previous meta-analysis, 17 studies were analyzed corresponding to 6640 patients. The odds ratio (OR) for seroreversion in children treated with benznidazole vs P/nT was 38.3 (95%CI: 10.7-137) and 34.9 (95%CI: 1.96-624.09) in RCT and OBS, respectively. In adults the OR for seroreversion in OBS was 17.1 (95%CI: 2.3-129.1). CP was only evaluated in adults, where benznidazole did not demonstrate a beneficial effect: OR 0.93 (95%CI: 0.8-1.1) and OR 0.49 (95%CI:0.2-1.2) for RCT and OBS, respectively. Most outcomes were deemed to have a low level of certainty, except for the beneficial effect in children and the low efficacy in adults (moderate certainty).

Conclusions: Benznidazole should be recommended for CCD in children, though this is only based on serological response and a moderate grade of evidence, while in adults benznidazole efficacy remains uncertain. More data on clinical efficacy of benznidazole in CCD is needed in both children and adults.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Flow diagram for selected studies.
Fig 2
Fig 2. Evaluation of the effect of benznidazole compared with placebo or no treatment on the response to therapy in children according to serological primary endpoint by type of study.
RCT: Randomized Clinical Trial; OBS: prospective observational study. References: [45], [38], [41].
Fig 3
Fig 3. Evaluation of the effect of benznidazole compared with placebo or no treatment on the response to therapy in adults according to serological primary endpoint by type of study.
RCT: Randomized Clinical Trial; OBS: prospective observational study. References: [44], [18], [47], [48].
Fig 4
Fig 4. Evaluation of the effect of benznidazole compared with placebo or no treatment on the response to therapy in adults according to clinical primary endpoint by type of study.
RCT: Randomized Clinical Trial; OBS: prospective observational study. References: [21], [42], [18], [47], [48].
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Publication types

Grants and funding

This research was supported by CIBER -Consorcio Centro de Investigación Biomédica en Red- (CB 2021), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación and Unión Europea – NextGenerationEU. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.