Activity of benzimidazoles againstDientamoeba fragilis(Trichomonadida, Monocercomonadidae)in vitroand correlation of beta-tubulin sequences as an indicator of resistance

Abstract

Recently, Dientamoeba fragilis has emerged as a significant and common enteropathogen. The majority of patients with dientamoebiasis present with gastrointestinal complaints and chronic symptoms are common. Numerous studies have successfully demonstrated parasite clearance, coupled with complete resolution of clinical symptoms following treatment with various antiparasitic compounds. Despite this, there is very little in vitro susceptibility data available for the organism. Benzimidazoles are a class of antiparasitic drugs that are commonly used for the treatment of protozoan and helminthic infections. Susceptibility testing was undertaken on four D. fragilis clinical isolates against the following benzimidazoles: albendazole, flubendazole, mebendazole, nocodazole, triclabendazole and thiabendazole. The activities of the antiprotozoal compounds at concentrations ranging from 2 μg/mL to 500 μg/mL were determined via cell counts of D. fragilis grown in xenic culture. All tested drugs showed no efficacy. The beta-tubulin transcript was sequenced from two of the D. fragilis isolates and amino acid sequences predicted a susceptibility to benzimidazoles. This is the first study to report susceptibility profiles for benzimidazoles against D. fragilis, all of which were not active against the organism. This study also found that beta-tubulin sequences cannot be used as a reliable marker for resistance of benzimidazoles in D. fragilis.

Paromomycin is superior to metronidazole in Dientamoeba fragilis treatment

“…To date, studies of the effectiveness of treatment of D. fragilis have been small (most include fewer than 100 subjects), they tend to study a heterogeneous population (studies in children, children and adults and adults), and generally include retrospective case series (CDC-Centers for Disease Control, 2017; van Gestel et al, 2018). The eradication rates reported vary greatly, with elevated rates of therapeutic failure (up to 80%) (Nagata et al, 2012; Stark et al, 2014; van Gestel et al, 2018). With regard to the antiparasitic drugs used, metronidazole has been studied more frequently, with eradication rates ranging from 52% to 85% (Banik et al, 2011; Engsbro et al, 2012; Kurt et al, 2008; Röser et al, 2014; Schure et al, 2013; Damien Stark et al, 2010; van Hellemond et al, 2012).…”

“…The transmission and biological cycle of D. fragilis have not been reported, although fecal–oral transmission is most probable (Munasinghe et al, 2013; Stark et al, 2016). In recent years, a cystic form of infection has been reported, which may explain how D. fragilis remains in the environment and could be a vehicle that mediates transmission between hosts (Stark et al, 2014).…”

“…Many therapeutic options for the treatment of infection by D. fragilis have been adopted in symptomatic cases. The main groups of antiparasitic drugs include: the nitroimidazoles, among which metronidazole and also secnidazole, tinidazole and ornidazole are of note (Banik et al, 2011; Girginkardeşler et al, 2003; Kurt et al, 2008; Röser et al, 2014; Stark et al, 2014); aminoglycosides, with paromomycin (Vandenberg et al, 2007; van Hellemond et al, 2012); hydroxyquinolines, such as iodoquinol and clioquinol (Spencer, 1979; Millet et al, 1983; Stark et al, 2010a, Stark et al, 2010b; Schure et al, 2013) and tetracyclines (Preiss et al, 1990). In vitro studies of antiparasitic drugs do not seem to correspond with clinical responses observed in humans (Chan et al, 1994; Nagata et al, 2012).…”

Dientamoeba fragilis, the Neglected Trichomonad of the Human Bowel

“…The activity of several benzimidazoles against D. fragilis was tested in vitro using four clinical isolates (198). Susceptibility testing showed that albendazole, flubendazole, mebendazole, nocodazole, triclabendazole, and thiabendazole had no effect against Dientamoeba.…”

“…Two beta-tubulin transcripts were sequenced from a clinical isolate of D. fragilis genotype 1, and the amino acid sequences of each beta-tubulin predicted susceptibility to benzimidazoles. This suggests that beta-tubulin sequences cannot be used as reliable markers for prediction of resistance to benzimidazoles in trichomonads (198). It should be noted that while Trichomonas and Giardia are susceptible to benzimidazoles, H. meleagridis is resistant, although the exact mechanism of resistance remains unknown (198).…”