Supplementary file 1_Efficacy and safety of different drugs for the treatment of leishmaniasis: a systematic review and network meta-analysis.docx

ObjectivesLeishmaniasis is a vector-borne neglected tropical infectious disease hat can be fatal if visceral leishmaniasis is left untreated. At present, many drugs have been used to treat leishmaniasis. This study aims to compare the efficacy and safety of different drugs to treat leishmaniasis through a network meta-analysis.
MethodsAll studies were retrieved from PubMed, Embase, and Cochrane databases, and the search time was from the date of database establishment to February 21, 2024. We assessed rates of clinical cure, mortality, and adverse effects (diarrhea, vomiting, injection site pain, and liver-enzyme abnormalities). We performed subgroup analyses of rates of clinical cure according to geographic region. All statistical analyses were performed using R and STATA 14.0 software for network meta-analysis. PROSPERO registration number: CRD42023478585.
Results12 articles with 2483 patients were included in this study, and the therapeutic effects of 5 drugs were evaluated. The results of the network Meta-analysis showed that the clinical cure rate of miltefosine, pentavalent antimony, and paromomycin was inferior to amphotericin B (RR 0.31; 95%CI 0.07-11.4, RR 0.23; 95%CI 0.04-1.39, RR 0.12; 95% CI 0.01-1.55), and amphotericin B may have the highest clinical cure rate. The mortality of pentavalent antimony was higher than that of amphotericin B and miltefosine (RR 4.81; 95%CI 0.42-41.45, RR 3.75; 95% CI 0.57-24.74), pentavalent antimony may be the drug with the highest mortality during treatment. About adverse effects, vomiting, and diarrhea were most common with miltefosine, and pain at the injection site and abnormalities in aspartate aminotransferase and alanine aminotransferase were most common with paromomycin. Subgroup analysis showed that clinical cure rates using Pentavalent antimony treatment were better in Brazil than in Ethiopia and India.
ConclusionsThis systematic review and network meta-analysis provide a new comparative framework for the clinical management of leishmaniasis. The results of network meta-analysis suggest that amphotericin B may be the first choice for the treatment of leishmaniasis, pentavalent antimony may be the drug with the highest mortality during treatment, miltefosine causes the highest incidence of gastrointestinal reactions, and paromomycin causes the highest incidence of injection site pain, aspartate aminotransferase, and alanine aminotransferase abnormalities. More high-quality studies are still needed to further determine the optimal drug for the clinical treatment of leishmaniasis in the future.
Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42023478585.