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Dientamoeba fragilis: plaints come to light. The organism has a median age of 41 years for all patients been isolated from patients with clinical submitting samples (mean 40.8 yr), an emerging role in disease in countries around the world, which suggests that sample bias does including an Australian study reporting not account for the observation of dif- intestinal disease that all of 60 patients with confirmed D. ferences in the incidence of this para- fragilis infection were symptomatic.3 site in younger people. irst described in 1918 by Jepps Moreover, treatment with drugs known Specimens from patients 11–15 years and Dobell, Dientamoeba fragi- to have parasiticidal activity in vitro has of age had relatively high rates of posi- F lis is a binucleated, unflagellated led to prompt and dramatic clinical im- tive reports (boys 10.3%, girls 9.6%). protozoan related to the trichomon- provement in the majority of reported Those from young men aged 16–20 ads,1 readily identified in stool speci- cases.1,2 In some cases, patients with years had the highest rate: 11.5% (95% mens by means of routine iron-hema- prior misdiagnoses of irritable bowel confidence interval [CI] 4%–19%). The toxylin stains. First observed in 7 syndrome (IBS) or chronic positivity rate of specimens from young patients, of whom 6 had diarrhea or have been found to be infected with the women aged 16–20 years, on the other , the parasite was dubiously parasite and cured with hand, was much lower (1.1%, 95% CI classified as a nonpathogen based on agents.1 Such observations indicate a 0.3%–1.9%; p < 0.01), in contrast with its source of nutrition: its voracious ap- need not only for appropriate investiga- reports from other countries1,2 where a petite is for the commensal of tion but also treatment of patients who female predilection has been sugges- the gut rather than the tissues of its have symptoms of irritable bowel syn- ted. Furthermore, 45.9% of positive re- host.1 For decades, the organism was drome before a reputedly incurable con- sults applied to specimens from female thrown into the grab-bag of human dition is diagnosed. As a result of these patients, who furnished 58.3% of the commensal with the likes of and other observations, many countries specimens submitted (p = 0.03). Adults coli and nana. have finally recognized D. fragilis as a over 20 years of age had the lowest inci- Questions about the nonpathogenicity true gastrointestinal .1 dence rates (0.6–2.0%); the rates in

5 of this protozoan have emerged, how- The prevalence of D. fragilis would children under 10 were intermediate 6 2

0 ever, and there can now be little doubt surprise most clinicians. A review of (1.3%–5.7%). Incidence rates showed 6 0

. 1–3 j a of its role in gastrointestinal disease. stool-examination reports at the Cad- no seasonal variation over a 5-year pe- m c

/ Only recently has the evidence sup- ham Provincial Laboratory in Winnipeg, riod (data not shown), which contrasts 3 0 5

1 porting D. fragilis as a cause of diar- which handles 80%–90% of stool ex- sharply with the summer–fall seasonal- . 0 1

: rhea, , cramping and aminations for parasites done in Mani- ity of traditionally associated I O

D a plethora of vague abdominal com- toba, revealed that the incidence of this with contaminated water (e.g., G. lam- parasite was second only to Blastocystis blia/intestinalis, C. parvum). Blastocystis hominis hominis and far in excess of more com- The mode of transmission of D. fra- monly incriminated parasites such as gilis remains a mystery, perhaps be- Giardia lamblia/intestinalis, Enta- cause its acknowledgement as a patho- moeba histolytica/dispar and Crypto- gen is so recent. The organism has Giardia lamblia/intestinalis sporidium parvum. Coinfection with B. never been found to have a cyst stage, /dispar hominis and D. fragilis was also com- deemed necessary for efficient feco-oral 1–3 Cryptosporidium parvum mon (Fig. 1). transmission. Moreover, direct trans- Entamoeba vermicularis To examine the epidemiology of D. mission via trophozoite forms was fragilis infection in Manitoba, we re- deemed unlikely when, in keeping with Dientamoeba latum viewed the examination results for all a longstanding practice among early Ascaris lumbricoides fecal specimens submitted over a 12- parasitologists of self-experimentation, B. hominis—D. fragilis coinfection month period (Feb. 2005 through Jan. Dobell swallowed a culture containing 2006) to the Cadham Provincial Labo- millions of trophozoites.1 Not only did 0 100 200 300 400 ratory for ova and parasites: a total of he remain asymptomatic, but for 10 No. of specimens positive for parasites 11 100 specimens from 6363 patients years he examined his own stool speci- (mean 1.74 specimens per patient). The mens and never observed the parasite. Fig. 1: Nonrepeat occurrence of the 8 parasite was found predominantly in Because of its morphological, bio- most common intestinal parasites di- specimens from young adults: 50% of logical and genetic similarities to pro- agnosed via stool examination at Cad- people found to have tozoan parasites of nonhuman animals ham Provincial Laboratory, Winnipeg, Man., over a 1-year period. in Manitoba were younger than 24 that are known to use the eggs of para- (mean 28.7) years. This contrasts with sitic worms as vectors, it was speculated

CMAJ • August 29, 2006 • 175(5) | 468 © 2006 CMA Media Inc. or its licensors Analysis

infections with Enterobius and Dienta- found in all patients with gastrointesti- Table 1: Treatments that have moeba, but appropriate testing (sticky nal complaints. Furthermore, people exterminated * Dientamoeba fragilis tape or paddle) for Enterobius eggs was who have symptoms of IBS should be Agent Dose, mg† Duration, d not performed consistently. Lastly, PCR evaluated for the presence of this and of nucleic acid extract of Enterobius other parasites. Where required, treat- Iodoquinol 650 20 eggs did not identify Dientameoba ment should be provided before a diag- , DNA in coinfected individuals.4 As it nosis of IBS is given. 100 10 twice a day stands, although the mode of transmis- 500 10 sion remains unknown, it seems fair to Philippe R. Lagacé-Wiens Department of Medical Microbiology , query the role of Enterobius in the 8–12 7 mg/kg body wt transmission of Dientamoeba. and Infectious Diseases University of Manitoba Secnidazole, Several drugs are thought to have 2000 1 Paul G. VanCaeseele single dose paraciticidal activity against D. fragilis. Unfortunately, in vitro testing is in- Department of Medical Microbiology Note: wt = weight. accurate and cannot reliably predict and Infectious Diseases *Adapted from references 1, 2 and 5–9. University of Manitoba †Administered by mouth: 3 times per day, unless treatment outcomes because Dienta- Cadham Provincial Laboratory otherwise indicated. moeba requires xenic media (media Cliff Koschik containing bacteria for the parasite to Cadham Provincial Laboratory that D. fragilis may also be transmitted feed on). Furthermore, no large-scale Winnipeg, Man. that way.1 Early studies pointed toward randomized control trials have been the pinworm, Enterobius vermicularis, done. Many agents have, however, led This article has been peer reviewed. as a potential vector: coinfection with to the eradication of D. fragilis from D. fragilis and E. vermicularis initially stools and resolution of symptoms as Competing interests: None declared. appeared to be far more common than documented in case reports (Table expected; amoeboid bodies resembling 1).1,2,5–9 The most commonly employed D. fragilis have been described in the and best studied treatments currently REFERENCES 1,8 1. Johnson EH, Windsor JJ, Clark CG. Emerging from eggs of E. vermicularis; and the parasi- are iodoquinol and doxycycline. This obscurity: biological, clinical, and diagnostic as- tologist Ockert (again, in the tradition regimen was studied in a small case pects of Dientamoeba fragilis. Clin Microbiol Rev of self-experimentation) successfully series of 21 people with IBS-like symp- 2004;17:553-70. 2. Norberg A, Nord CE, Evengard B. Dientamoeba infected himself and 2 other adult vol- toms and concomitant infection with fragilis — a protozoal infection which may cause unteers by ingesting E. vermicularis D. fragilis who were treated with iodo- severe bowel distress. Clin Microbiol Infect 2003; 9:65-8. eggs taken from a child coinfected quinol and doxycycline: the symptoms 3. Stark D, Beebe N, Marriott D, et al. Prospective with D. fragilis.1 resolved in 14 of the patients (67%), in study of the prevalence, genotyping, and clinical relevance of Dientamoeba fragilis infections in an Despite these observations, many whom the organism was eradicated. In Australian population. J Clin Microbiol 2005;43: have questioned a role for pinworms in a more recent study of secnidazole 2718-23. 9 4. Menghi CI, Makiya R, Gatta CL, et al. Dientamoeba transmission, frequently citing the pau- treatment, a single dose eradicated fragilis: molecular biology techniques for the eluci- city of well-controlled epidemiological the parasite in 34 of 35 patients (97%, dation of its mode of transmission. Parasitol Lati- experiments.1 In one study, Stark and 95% CI 92%–100%) and resolved clini- noam 2005;60:25-31. 5. Dardick KR. Tetracycline treatment of Dientamoe- 3 colleagues performed appropriate pin- cal symptoms in 27 cases (77%, 95% ba fragilis. Conn Med 1983;47:69-70. worm testing in conjunction with mi- CI 63%–91%). 6. Spencer MJ, Garcia LS, Chapin MR. Dientamoeba fragilis: an intestinal pathogen in children? Am J croscopic stool examination and found Intestinal parasites, particularly Dis Child 1979;133:390-3. no association between infection with those found in temperate climates, are 7. Cuffari C, Oligny L, Seidman EG. Dientamoeba fragilis masquerading as allergic . J Pediatr Enterobius and Dientamoeba. The au- often forgotten as causes of disease. Gastroenterol Nutr 1998;26:16-20. thors acknowledged, however, that Increasing evidence of pathogenicity in 8. Borody T, Warren E, Wettstein A, et al. Eradication of Dientamoeba fragilis can resolve IBS-like symp- spontaneous remission of pinworm common parasites previously deemed toms. J Gastroenterol Hepatol 2002;17(Suppl):A103. infection could have occurred while Di- as nonpathogenic, including D. fragil- 9. Girginkardesler N, Coskun S, Cuneyt Balcioglu I, et al. Dientamoeba fragilis, a neglected cause of di- entamoeba infection persisted. Similar- is, should prompt clinicians to con- arrhea, successfully treated with secnidazole. Clin ly, our study did not identify any co- sider eradicating D. fragilis when it is Microbiol Infect 2003;9:110-3.

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CMAJ • August 29, 2006 • 175(5) | 469