INTRODUCTION — Dientamoeba fragilis is an anaerobic intestinal protozoan parasite. Historically, this organism was among a group of enteric protozoan parasites beginning with Giardia duodenalis (previously G. lamblia) that were initially believed to be commensals and not capable of causing symptomatic illness. As more information became available and antimicrobial agents were developed with activity against these parasites, it became clear that D. fragilis can cause an active infection, although it does not always result in symptomatic disease. (See "Giardiasis: Epidemiology, clinical manifestations, and diagnosis" and "Blastocystis species" and "Nonpathogenic enteric protozoa".)
It is controversial whether D. fragilis is a pathogen or a commensal parasite [1,2]. In some studies, detection of D. fragilis in stool has been observed more frequently among asymptomatic individuals than among symptomatic patients [3-5]. Moreover, the means by D. fragilis is transmitted has not been fully defined. Finally, the diagnostic recognition of this parasite in stool examinations requires specific processing; thus, it is possible that many infections may go undiagnosed.
MICROBIOLOGY — Ultrastructural, immunologic, and genetic analyses place D. fragilis in the family of protozoan flagellates, which includes Trichomonas [1,6]. Unlike other intestinal protozoan organisms that have both trophozoite and hardy cyst stages, for a long time D. fragilis was recognized to exist only as trophozoites. Trophozoites measure 7 to 12 micrometers in diameter, contain one or two nuclei, lack flagellae, and are minimally motile. However, cyst forms of D. fragilis have been identified in experimental mouse infections and in human fecal samples [7], suggesting that cystic forms are the transmissible infectious form of this organism.
There is genetic evidence for two variants of D. fragilis (genotypes [1 and 2]). There is a strong predominance of genotype 1 in both humans and few animal hosts [8]. It is unknown if these two differ in their pathogenicity [9], although studies have shown very low levels of genetic variability across parasite isolates collected in various geographic areas and from both symptomatic and asymptomatic cases [8].
EPIDEMIOLOGY — Infections with D. fragilis are acquired by the fecal-oral route, but how fragile trophozoites survive outside of the body and do not succumb to stomach acid following ingestion are not fully understood (figure 1). Some investigators suggested that trophozoites might survive within and be ingested with the eggs of the pinworm Enterobius vermicularis. While this might explain coinfection in some children, it does not likely explain most D. fragilis infections. In addition, some studies have specifically failed to find a correlation between D. fragilis and E. vermicularis infections [10]. The recognition of cyst forms of the parasite may be important for understanding transmission [7]. In addition, sheep, pigs, and nonhuman primates have been identified as natural hosts of the genotypes found in humans, suggesting zoonotic potential for human transmission [11]. (See "Enterobiasis (pinworm) and trichuriasis (whipworm)".)
D. fragilis is distributed globally; the prevalence varies with geography [12-20]. In series from different countries, D. fragilis was detected in approximately 5 percent of stool samples submitted for diagnostic examination in the United States and Australia [10,12,21], 5 percent in the Sultanate of Oman [15], and 8 percent in the Netherlands among patients with diarrhea lasting more than a week [16]. D. fragilis has been detected in returned missionaries [18], patients with traveler's diarrhea [20], and immigrants [22].
Many diagnostic laboratories lack the requisite procedures to detect D. fragilis, since trophozoites deteriorate rapidly and can therefore be missed by microscopy unless there is prompt fixation of the specimen [12,14]. In a report from Ottawa, Canada, 91 percent of healthy children had detectable serum antibodies to D. fragilis, suggesting that mild or subclinical infections were common during childhood (though cross-reactivity is possible) [23]. Another report from rural Venezuela noted a 40 percent prevalence of D. fragilis with use of combined microscopy–polymerase chain reaction (compared with 16 percent for microscopy alone) [24]. Thus, microscopy probably underestimates the prevalence of D. fragilis, but the increasing use of nucleic acid detection techniques is changing this. In a Finnish study including refined microscopic criteria and polymerase chain reaction testing, D. fragilis was found to be the most common intestinal protozoan [25].
In addition to geography, other factors may favor D. fragilis infection, such as rural residence and pet exposure [26]. However, the data from different regions are conflicting as to whether infection is more common in females [27] or males [28,29]. It is also unclear whether or not there is seasonal variation [27,29].
CLINICAL MANIFESTATIONS — The clinical presentation with D. fragilis is variable. Many individuals with D. fragilis are asymptomatic; the most common symptomatic presentation consists of gastrointestinal illnesses. The incubation period prior to the onset of symptoms following infection is unknown, as is the proportion of infected people who remain asymptomatic.
In one systematic review of individuals with D. fragilis in stool, 6 to 86 percent had diarrhea [2]. In 11 studies of stool samples submitted to laboratories, 4 percent of individuals had D. fragilis, of whom 54 percent had diarrhea.
The parasite localizes in the colon and can cause colitis [30]. Common complaints in those who are symptomatic include abdominal pain, flatulence, acute and recurrent diarrhea, or loose stools [1,10,13,27,28,30-32]. In one review, most patients presented with diarrhea and abdominal pain, frequently lasting longer than a duration of two weeks [21]. In one study of Turkish patients infected with D. fragilis, symptoms included [13]:
●Abdominal pain – 81 percent
●Diarrhea – 72 percent
●Anorexia – 16 percent
●Fatigue – 9 percent
●Nausea – 6 percent
●Weight loss – 3 percent
●Vomiting – 3 percent
In one study, patients with D. fragilis experienced abdominal pain (28 percent), anal itching (27 percent), watery diarrhea (19 percent), meteorism (16 percent), and nausea/loss of appetite (14 percent) [33]. Abdominal pain and diarrhea presumed to be attributable to D. fragilis infections may persist for several years [1,10,13,15,28,31]. D. fragilis infection may be observed in some patients fulfilling criteria for irritable bowel syndrome [34], although one meta-analysis found no significant association [35]. (See "Clinical manifestations and diagnosis of irritable bowel syndrome in adults".)
Children are susceptible to infection with D. fragilis and may present with clinical symptoms (especially diarrhea and abdominal pain) more frequently than adults; they may also have prolonged infection [36,37]. Peripheral blood eosinophilia may accompany D. fragilis infections [22,30,31,33,38], and an eosinophil-enriched colitis due to D. fragilis infection may be mistaken for allergic colitis [30]. Neither the mechanism of the eosinophilia nor any pathophysiologic sequelae of the eosinophilia are known. The presence of eosinophilia in this infection is in striking contrast with disease caused by other intestinal protozoa, with the exception of Isospora belli infections. (See "Epidemiology, clinical manifestations, and diagnosis of Cystoisospora (Isospora) infections" and "Approach to the patient with unexplained eosinophilia".)
DIAGNOSIS — The diagnosis of D. fragilis traditionally rests with detection of trophozoites in microscopic examinations of fixed and stained stool samples [1]. Trophozoites are fragile and are not detectable on wet mounts, iodine-stained samples, or formalin-ethyl acetate concentrates [13]. Thus, fixation of stool samples in polyvinyl alcohol fixative, sodium acetate-acetic acid-formalin fixative, or Schaudinn's fixative is necessary, as is the use of permanent trichrome staining [14,32].
Giemsa-stained stool smears may be helpful in detecting D. fragilis [36]. There are no available D. fragilis immunofluorescent or antigen assays that can be used in lieu of conventional microscopic evaluation. Specific cultivation methods have been shown effective in the detection of D. fragilis in stool but are not commonly available [1,39,40].
Conventional and real-time polymerase chain reaction (PCR) methods have been developed that have significantly higher sensitivity and specificity than microscopy [1,24,41-46]. PCR-based assays have been developed and are being increasingly used to concurrently detect D. fragilis as well as Blastocystis, Cryptosporidium, Giardia, Entamoeba, and other pathogens in human stool samples [47,48].
DIFFERENTIAL DIAGNOSIS
●Gastrointestinal symptoms – Other protozoal parasites including giardiasis and Blastocystis can cause similar symptoms of abdominal pain, diarrhea, and anorexia. These are distinguished from D. fragilis via stool microscopy, immunoassay, or polymerase chain reaction. (See "Giardiasis: Epidemiology, clinical manifestations, and diagnosis" and "Blastocystis species".)
●Gastrointestinal symptoms and eosinophilia – Other causes of gastrointestinal symptoms and eosinophilia include isosporiasis, strongyloidiasis, ascariasis, and hookworm. Coinfection can occur; the diagnoses are distinguished by stool microscopy. (See "Strongyloidiasis" and "Ascariasis" and "Hookworm infection".)
●Irritable bowel syndrome – Clinical manifestations of irritable bowel syndrome include chronic abdominal pain and altered bowel habits, including diarrhea or constipation. The diagnosis is established based on clinical criteria. (See "Clinical manifestations and diagnosis of irritable bowel syndrome in adults".)
TREATMENT
Clinical approach — While identification of D. fragilis in an asymptomatic individual generally requires no treatment, infections with D. fragilis should be treated when the organism is found as a sole pathogen in stool samples from patients with abdominal pain or diarrhea lasting for more than one week.
No large-scale randomized controlled trials have been performed to assess the effect of various antimicrobial agents in patients infected with D. fragilis [49]. There are several regimens that may be used to treat D. fragilis infections, including [31,37,50,51]:
●Metronidazole (500 to 750 mg three times a day for 10 days)
●Paromomycin (25 to 35 mg/kg per day in three divided doses for 7 days)
●Iodoquinol (650 mg three times a day for 20 days)
●Tetracycline (500 mg [10 mg/kg] orally four times daily for 10 days) or doxycycline (100 mg [2 mg/kg] orally twice daily for 10 days)
In a study evaluating the in vitro susceptibility of D. fragilis to several antiparasitic agents, 5-nitroimidazole derivatives were found to be the most active compounds (including ornidazole, tinidazole, metronidazole, and secnidazole), followed by nitazoxanide, tetracyclines, furazolidone, iodoquinol, paromomycin, and diloxanide furoate [52]. Benzimidazoles (albendazole, mebendazole) have no activity in vitro against D. fragilis [53].
Another study included 96 children with D. fragilis infection and chronic gastrointestinal symptoms treated with a 10-day course of metronidazole or placebo; eradication of D. fragilis was significantly greater in the metronidazole group as assessed by polymerase chain reaction (PCR) 14 days after completion of therapy, although PCR positivity rebounded by eight weeks after completion of therapy to levels comparable with those seen in placebo recipients [54]. Change in gastrointestinal symptoms following treatment did not differ significantly between the groups.
Data suggest paromomycin is efficacious despite relatively weak in vitro susceptibility data as well as a lack of randomized controlled trial data [21,55]; one report noted eradication rates of 98 percent [56]. In one study from Italy including 85 patients, the rate of clinical improvement was higher among those treated with paromomycin compared with metronidazole (53 versus 100 percent) [33].
Iodoquinol has traditionally been used quite commonly, but its availability is declining.
Other agents — In addition to metronidazole, other nitroimidazole agents with potential efficacy include secnidazole, ornidazole, and tinidazole.
Secnidazole was evaluated in a study of 35 Turkish patients with D. fragilis infection; in all but one patient, the organism was eradicated with a single dose of secnidazole, suggesting that secnidazole is effective in achieving parasitological and clinical cure [13].
Ornidazole (30 mg/kg single dose for children and 2 g single dose for adults) was superior to metronidazole in a randomized trial of 112 Turkish patients with respect to parasitologic cure (92.9 versus 69.6 percent, p = 0.001) and clinical cure (96.4 versus 76.8 percent, p = 0.001) [57].
Tinidazole (2 g single dose) is more widely available than the above agents and is better tolerated than metronidazole; use of this agent is reasonable although data are limited. It may be effective in combination with paromomycin or other agents; further study is needed [21,55].
PREVENTION — Since the mechanism of D. fragilis transmission is not fully understood, there are no specific guidelines on measures to prevent acquisition of infection with this organism. Screening of household members of D. fragilis patients has been suggested [38,58], especially in cases of relapsed infection.
SUMMARY AND RECOMMENDATIONS
●Dientamoeba fragilis is an anaerobic intestinal protozoan parasite. It is a flagellate that produces trophozoites as well as cysts. Infection may be symptomatic or asymptomatic. (See 'Introduction' above and 'Microbiology' above.)
●Infection is transmitted by the fecal-oral route. D. fragilis is distributed globally but the prevalence varies with geography. Since many diagnostic laboratories lack the requisite procedures for detection, the prevalence is probably underestimated. (See 'Epidemiology' above.)
●The incubation period and proportion of asymptomatic infected individuals are unknown. The parasite localizes in the colon and can cause colitis. Common symptoms include abdominal pain and acute and recurrent diarrhea. D. fragilis may present with peripheral eosinophilia and/or eosinophilic colitis. (See 'Clinical manifestations' above.)
●The diagnosis is made via detection of D. fragilis trophozoites in microscopic examinations of appropriately fixed and stained stool samples or by polymerase chain reaction–based techniques. (See 'Diagnosis' above.)
●Treatment is warranted when the organism is found as a sole pathogen in stool samples in the setting of abdominal pain or diarrhea lasting more than one week. The optimal therapy is uncertain; we suggest treatment with metronidazole or paromomycin (Grade 2C). (See 'Treatment' above.)
