title: Metronidazole therapy for treating dientamoebiasis in children is not associated with better clinical outcomes: a randomized, double-blinded and placebo-controlled clinical trial.
abstract: BACKGROUND
  There is a paucity of evidence documenting the pathogenicity of Dientamoeba fragilis, an intestinal protozoan common in children. As case reports on successful treatment are numerous, many authors advocate treatment, despite no placebo-controlled trials being available. Metronidazole is often used for treatment, though eradication rates are relatively low (60%-80%). In the present study we determined the clinical and microbiological efficacy of metronidazole in Danish children.
  
  
  METHODS
  In this parallel placebo-controlled double-blinded trial, children aged 3-12 years with >4 weeks of gastrointestinal symptoms were allocated using block randomization in a 1:1 ratio to a 10-day course of oral metronidazole or placebo. Primary outcome was change in level of gastrointestinal symptoms, measured on a visual-analog-scale (VAS), and secondary outcome was eradication of D. fragilis infection. Participants, caregivers, investigators, and sponsor were all blinded to group assignment. The trial was registered with clinicaltrials.gov (NCT01314976) prior to start.
  
  
  RESULTS
  Of 96 participants, 48 were allocated to the metronidazole and placebo group each. Mean VAS change from pre- to post-treatment did not differ significantly (P = .8) between the metronidazole (-1.8 CI, [-2.5, -1.1]) and the placebo group (-1.6 CI, [-2.3, -.9]). Eradication of D. fragilis was significantly greater in the metronidazole group, although it declined rapidly from 62.5% 2 weeks after end of treatment to 24.9% 8 weeks after end of treatment.
  
  
  CONCLUSIONS
  These findings do not provide evidence to support routine metronidazole treatment of D. fragilis positive children with chronic gastrointestinal symptoms. Study funded by Statens Serum Institut.
  
  
  BACKGROUND
  Trial was registered with clinicaltrials.gov (NCT01314976).
authors.affiliation: Department of Microbiology and Infection Control.
authors.forename: Dennis
authors.initials: D
authors.lastname: Röser
authors.affiliation: Division of Health Surveillance and Research, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Jacob
authors.initials: J
authors.lastname: Simonsen
authors.affiliation: Department of Microbiology and Infection Control.
authors.forename: Christen Rune
authors.initials: CR
authors.lastname: Stensvold
authors.affiliation: Department of Microbiology and Infection Control.
authors.forename: Katharina E P
authors.initials: KE
authors.lastname: Olsen
authors.affiliation: Faculty of Health Sciences, Department of Medicine, Copenhagen University, Køge University Hospital, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Bytzer
authors.affiliation: Department of Microbiology and Infection Control.
authors.forename: Henrik V
authors.initials: HV
authors.lastname: Nielsen
authors.affiliation: Division of Health Surveillance and Research, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Kåre
authors.initials: K
authors.lastname: Mølbak
mesh_terms: D000890:Anti-Infective Agents / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D003718:Denmark; D004030:Dientamoebiasis / Q000150:complications / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008795:Metronidazole / Q000627:therapeutic use*; D012720:Severity of Illness Index
chemical_list: D000890:Anti-Infective Agents; D008795:Metronidazole
keywords: Dientamoeba fragilis; RCT; antimicrobial; pathogenicity; pediatric