Therapeutic efficacy and safety of antileishmanial agents for visceral leishmaniasis in children: A systematic review

Abstract

Objective: To evaluate the dosing, efficacy and safety of the main antileishmanial agents amphotericin B (conventional or liposomal), pentavalent antimonials, miltefosine and paromomycin recommended for the treatment of visceral leishmaniasis in children.

Methods: The efficacy and safety of visceral leishmaniasis treatments in children were systematically reviewed using literature from PubMed, Cochrane, clinicaltrials.gov, and Google Scholar, focusing on randomised trials with separate pediatric data (published from 2000-2024). The risk of bias of selected trials was assessed using the revised Cochrane risk-of-bias tool for randomised trials (RoB 2). Reporting was done per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 checklist.

Results: Of 1 186 records, only 7 were eligible for qualitative synthesis. Three trials exclusively included children. The treatment regimens studied showed high heterogeneity and lacked sufficient data for a meta-analysis. Most trial arms reported efficacies over 94% for children across different regimens. Miltefosine monotherapy showed the highest rate of late treatment failures, highlighting that allometric dosing is crucial to ensure proper drug exposure in children. Safety data for children were available in only three studies with varied reporting systems of adverse events. Although regimens in this review were generally considered to be safe in children, antimonial-related cardiac toxicity remains a threat.

Conclusions: This review highlights the need for pediatric-specific trials, clear presentation of pediatric data, and systematic documentation of adverse events to enhance evidence for policy-making and pediatric guideline development.

Keywords

Visceral leishmaniasis / Children / Treatments / Efficacy / Safety / Systematic review

Conflict of interest statement

The authors declare that they have no conflict of interest.

Funding

The authors received no extramural funding for the study.

Authors’ contributions

Concept, design and protocol development was by all authors; Literature search, article selection, and data acquisition was by NLDS and CSR; Independent data extraction was by NLDS and SR; Data analysis and Risk of bias assessment was by NLDS; Manuscript preparation by NLDS; Review of selected articles, editing and reviewing of the manuscript and resolving disagreements in the risk of bias judgement was by SR, MH and TCY. All authors read and approved the final manuscript.

Publisher’s note

The Publisher of the Journal remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Edited by Pan Y, Lei Y, Zhang Q

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