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

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. 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. Author summary: Chagas disease is a neglected parasitic disease, endemic in Latin America, where it poses a public health problem. Moreover, thanks to population movements, its presence has significantly increased in non-endemic areas, where it has high rates of under-diagnosis. The only two treatments currently available (benznidazole, generally the first choice, and nifurtimox) date from the 1960s and are poorly tolerated. Moreover, there is much uncertainty about their indication, dosage and benefits, especially in chronically infected adult populations. For this reason, we have update a meta-analysis published in 2009 on the effectiveness of benznidazole in chronic Chagas disease, analyzing data from 17 studies involving 6,640 patients. In the pediatric population the indication is well established thanks to some clinical trials carried out in the 1990s and the accumulated clinical experience so far. Most of the recent studies have been performed in adult populations; however, they provide low or very low certainty on the effectiveness of benznidazole except for patients with established cardiomyopathy, where benznidazole didn´t demonstrated benefit. We find that data on the treatment of indeterminate chronic infection are insufficient. Since no new drugs are expected in the near future, it would be desirable to launch trials with clinical outcomes and long follow-up periods to evaluate the efficacy of current drugs for the treatment of the indeterminate chronic Chagas disease.