Treatment for Dientamoeba fragilis: A Systematic Review and Meta-analysis

Abstract Introduction Dientamoeba fragilis (D. fragilis) is detected in stool tests of patients with gastrointestinal symptoms. Despite a debate over its pathogenicity, treatment is often prescribed, after excluding other reasons. The most commonly used therapy in practice is metronidazole; however, evidence to support this practice is limited. Methods We conducted a systematic review and meta-analysis compiling studies evaluating metronidazole vs any other regimen for the treatment of D. fragilis. Studies reporting treatment outcomes (clinical and/or microbiological) of D. fragilis regimens diagnosed by standard stool microscopy and polymerase chain reaction. We searched PubMed, Cochrane library, and Web of Science up to March 2025 for relevant studies. The primary outcome was clinical response; microbiological response was a secondary outcome. Results We included 12 comparative studies in the quantitative meta-analysis and additional non-comparative studies in the qualitative systematic review. Two studies were randomized controlled trials (RCT), and others were observational studies. Nine studies were included in the analysis of the primary outcome. Significantly higher clinical response rates were demonstrated with paromomycin (odds ratio [OR] 2.31, 95% confidence interval [CI] 1.37–3.89, without heterogeneity) and clioquinol (odds ratio [OR] 2.52, 95% confidence interval [CI] 1.26–5.05, without heterogeneity) compared to metronidazole therapy. Significantly higher microbiological response was demonstrated with paromomycin (OR 3.94, 95% CI 2.75–5.65) and a trend for higher response for clioquinol (OR 1.41, 95% CI 0.68–2.92), compared with metronidazole. Conclusions Limited data compiled in this meta-analysis supports the use of paromomycin or clioquinol for treatment of D. fragilis symptomatic infection, in case a decision to treat this pathogen is taken. Future studies correlating clinical efficacy with microbiological eradication are needed.