Treatment Outcomes in Symptomatic Dientamoeba fragilis Infection: A Prospective Clinical and Molecular Study

Purpose The clinical significance and optimal treatment of Dientamoeba fragilis (DF) infection remain controversial, despite its frequent detection in patients with chronic gastrointestinal symptoms. This study aimed to evaluate clinical and molecular responses to various antiparasitic regimens and to assess the association between symptom resolution and parasite eradication. Methods In this prospective, single-center observational study conducted between January 2019 and June 2023, we included 105 symptomatic patients with a positive stool PCR for DF. Patients were treated with paromomycin (PAR), nitroimidazole monotherapy (NM; metronidazole/tinidazole), or a combination of tinidazole and albendazole (T + A). Clinical and molecular outcomes were assessed one month post-treatment using a structured symptom questionnaire and repeat PCR testing. Results Of 96 patients with follow-up, 73 underwent repeat PCR testing. PAR was associated with significantly higher clinical and molecular cure rates (82.8% and 88.5%, respectively) compared to T + A (35.0% and 29.2%) and NM (4.2% and 10.0%). Combination therapy with T + A was superior to NM in clinical response but not in molecular clearance. A strong correlation was observed between clinical cure and DF eradication (p < 0.00001), reinforcing the pathogenic role of DF. Median symptom duration before referral was 9 months, indicating the chronic nature of untreated infection. Conclusions DF should be considered in patients with unexplained chronic gastrointestinal symptoms. Molecular testing is recommended for accurate diagnosis. Paromomycin appears to be the most effective treatment, with a strong association between clinical recovery and microbiological cure. Randomized controlled trials are warranted to further define optimal management strategies for DF infection.