Dientamoeba fragilis in children: a systematic review on diagnostic considerations and efficacy of treatment.

Introduction: The presence of D. fragilis in feces is characterized by an asymptomatic carrier ship to a spectrum of gastrointestinal symptoms. However, a causal relationship remains to be elucidated. In this systematic review, we aimed to evaluate the relationship between the eradication of D. fragilis and symptoms to establish the strength of evidence that D. fragilis in symptomatic children warrants antibiotic treatment.Areas covered: This systematic review covers a challenge in daily clinical practice. Is it necessary to test for D. fragilis in children with gastrointestinal symptoms and does a positive fecal PCR test warrant treatment?Expert opinion: Testing for D. fragilis seems justified in a selection of children with persistent unexplained chronic abdominal pain and diarrhea. Treatment of D. fragilis should be withhold until other causes like celiac disease have been excluded. Both microscopic and Real Time-PCR methods (or a combination of the two) can be used for diagnosis. Paromomycin or clioquinol are antibiotics of choice based on their small spectrum of activity, fewer side effects, and better eradication rates than metronidazole. Future randomized studies, with strict inclusion criteria, appropriate diagnostic testing, and doses of antibiotics based on bodyweight are warranted.

No association between abdominal pain and Dientamoeba in Dutch and Belgian children.

OBJECTIVE: To study the association between Dientamoebafragilis colonisation and faecal calprotectin to see whether the parasite is a harmless commensal or a gut pathogen. DESIGN: Cross-sectional study of previously collected stool samples. SETTING AND PATIENTS: Two hundred stool samples originated from children aged 5-19 years with chronic abdominal pain and diarrhoea, who were seen in paediatric clinics in the Netherlands and Belgium and in whom somatic gastrointestinal disorders were excluded. Another 122 samples came from a healthy community-based reference population of the same age. All stool samples were analysed with real-time PCR for the detection of D. fragilis and with an ELISA for calprotectin-a biomarker of gastrointestinal inflammation. MAIN OUTCOME MEASURES: Prevalence of D. fragilis colonisation and results of stool calprotectin testing. RESULTS: D. fragilis was detected in 45% (95% CI 38% to 51%) of patients and in 71% (95% CI 63% to 79%) of healthy children. Median (IQR) concentrations of calprotectin in patients and healthy children with a positive PCR result were not different from those with a negative PCR result (40 (40-55) µg/g vs 40 (40-75) µg/g, respectively). CONCLUSION: Since D. fragilis colonisation is most prevalent in healthy children and is not associated with an increase in faecal calprotectin concentration, our data do not support the inference that D. fragilis is a pathogenic parasite. Routinely testing for D. fragilis in children with chronic abdominal pain should therefore be discouraged.

[Dientamoeba fragilis infection in patients with gastrointestinal system complaints]. / Gastrointestinal sikayeti olan hastalarda dientamoeba fragilis enfeksiyonu.

In this study, we aimed to investigate the incidence of Dientamoeba fragilis with different diagnostic methods in patients with gastrointestinal symptoms and determine the sensitivity and specificity of existing diagnostic methods. Fecal samples collected from 101 patients with gastrointestinal complaints (especially upper abdominal pain, abdominal and pelvic pain, nausea and vomiting, gastroenteritis and colitis, unexplained fever and diarrhea) and 20 control cases from various clinics were included in the study. Samples were first examined with native-Lugol (N-L) method and cultured in Robinson medium. All 121 stool and culture samples were stained with iron hematoxylin stain (IHS) and trichrome stain (TS) methods and examined by PCR and QPCR for D.fragilis. Among 121 stool samples 13 (10.7%), 2 (1.7%), 7 (5.7%) 13 (10.7%), and 7 (5.8%), 4 (3.3%), 2 (1.7%), 3 (2.5%) of cultured samples were determined positive with IHS, TS, PCR, QPCR respectively. Fifteen of the 121 stool samples were determined as diarrheal. All diarrheal stool samples were negative with IHS and TS. One of the diarrheal stools and 6 (4.9%) of the non-diarrheal stools were positive by PCR. All of the diarrheal stools were negative. Thirteen of the non-diarrheal stool samples (10.7%) were positive by QPCR. When the QPCR method was considered as gold standard, sensitivity and specificity values were determined as 46% and 93% in IHS, 0% and 99% in TS, 54% and 100% by PCR and sensitivity and specificity values were 67% and 96% in IHS, 33% and 98% in TS, 67% and 100% by PCR among cultured stool samples. As a result, it was determined that there was a statistically significant difference between the samples of the patients and the control groups and the sensitivity and specificity of the conventional and molecular methods (IHS, TS, PCR and QPCR) determined in this study supported the results of other compared studies. It has been determined that staining methods used for the diagnosis of D.fragilis gave false positivite or negativite results. In addition, the QPCR method is more advantageous in terms of time saving for the diagnosis and initiation of the treatment and in cases where QPCR is not available, IHS and conventional PCR methods should be used together. In our opinion, this study will contribute to the results of epidemiological and scientific studies on D.fragilis in Turkey.

The role of Blastocystis sp. and Dientamoeba fragilis in irritable bowel syndrome: a systematic review and meta-analysis.

Irritable bowel syndrome (IBS) is globally one of the most prevalent gastrointestinal disorders with a negative impact on quality of life and socio-economic status of patients. Recently, controversial evidences suggest that Blastocystis sp. and Dientamoeba fragilis infections may be implicated in the development of IBS. We performed a systematic review and meta-analysis to examine the possible association regarding this issue. PubMed, ScienceDirect, Scopus, Web of Science, and Cochrane electronic databases were searched (up to February 2017) to identify the relevant studies. Pooled odds ratio (OR) and 95% confidence intervals were estimated using a random effects meta-analysis model on data from included studies. A total of 17 studies including 5882 participants (2527 patients and 3310 controls) met the eligibility criteria. Individuals with Blastocystis infection were found to have a positive association with IBS (OR, 2.19; 95% CI, 1.54-3.13), while this association was not observed for D. fragilis infection (OR, 1.13; 95% CI, 0.22-5.72). In subgroup analysis for Blastocystis infection, the pooled ORs were OR 2.29, 95% CI 1.55-3.41; OR 1.70, 95% CI 0.83-3.44; and OR 3.83, 95% CI 2.34-6.27 for hospital-based, healthy volunteers, and combined controls, respectively. Considering the subtypes, meta-analysis result demonstrated significant positive ORs for ST1 (OR, 4.40; 95% CI, 2.81-6.90) and ST3 (OR, 1.94; 95% CI, 1.36-2.77) to be potential risk factors for IBS. Our results support the existence of a positive association between Blastocystis sp. and IBS. Further studies with more sample size should be performed to better investigate the real impact of these parasites on the occurrence of IBS.

The persistence of chronic spontaneous urticaria in childhood is associated with the urticaria activity score.

BACKGROUND: There is little information regarding the etiology and natural course of chronic spontaneous urticaria (CSU) in childhood. OBJECTIVE: To investigate the etiology, prognosis, and the factors associated with the prognosis of CSU in children. METHOD: Data from children with CSU who had been diagnosed between 1992 and 2015 were analyzed. A telephone interview was done to assess the current status of these patients. Remission was defined as the disappearance of urticaria for >6 months. RESULTS: A total of 222 children with CSU were evaluated. The median age of symptom onset was 8.8 years (interquartile range [IQR], 4.6-12.3 years), median duration of urticaria was 23 months (IQR, 7-48 months), and the median sum of the daily urticaria activity score of 7 consecutive days (UAS7) was 28 (IQR, 21-42). Accompanying angioedema was reported by 107 patients (48.2%), whereas 27.1% of the study population had autoantibody positivity. Autologous serum skin testing results were positive in 43 (34.1%); skin-prick testing results revealed atopy in 55 children (27.9%). Parasites (4.8%), pollen sensitization (1.5%), food allergy (0.9%), urinary tract infection (0.9%), and Hashimoto thyroiditis (0.5%) were determined as etiologic factors of CSU. The patients were followed up for a median time of 15 months (IQR, 5-36.5 months). Remission was observed in 10.6, 29.3, and 44.5% of the patients in 1, 3, and 5 years, respectively. In multivariate regression analysis, a UAS7 of >28 at admission was found to be a risk factor for persistence of urticaria (odds ratio 6.22 [95% confidence interval, 1.54-25.15; p = 0.010). CONCLUSION: The etiology of CSU in children was mostly idiopathic despite detailed investigation. In childhood, the natural course of CSU was favorable, and nearly half of the patients recovered after 5 years of disease duration. A high UAS7 at admission seemed to be a significant risk factor for the persistence of symptoms.

Metronidazole therapy for treating dientamoebiasis in children is not associated with better clinical outcomes: a randomized, double-blinded and placebo-controlled clinical trial.

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. CLINICAL TRIALS REGISTRATION: Trial was registered with clinicaltrials.gov (NCT01314976).

Dientamoeba fragilis DNA detection in Enterobius vermicularis eggs.

Dientamoeba fragilis is an intestinal protozoan suspected of causing gastrointestinal symptoms, and its mode of transmission is unknown, although first described almost a century ago. A hypothesis is that Enterobius vermicularis is a vector for D. fragilis, and recently, D. fragilis DNA was detected within surface-sterilized eggs of E. vermicularis. Using real-time PCR, we detected D. fragilis DNA in 18 (85%) of 21 samples of E. vermicularis eggs collected from patients harbouring D. fragilis in faeces. This finding supports the hypothesis that E. vermicularis may have an important role in the transmission of D. fragilis.

A case-controlled study of Dientamoeba fragilis infections in children.

Dientamoeba fragilis is a pathogenic protozoan parasite that is implicated as a cause of human diarrhoea. A case-controlled study was conducted to determine the clinical signs associated with D. fragilis infection in children presenting to a Sydney Hospital. Treatment options are also discussed. Stool specimens were collected from children aged 15 years or younger and analysed for the presence of D. fragilis. In total, 41 children were included in the study along with a control group. Laboratory diagnosis was performed by microscopy of permanently stained, fixed faecal smears and by real-time PCR. Gastrointestinal symptoms were present in 40/41 (98%) of these children with dientamoebiasis, with diarrhoea (71%) and abdominal pain (29%) the most common clinical signs. Chronic gastrointestinal symptoms were present in 2% of cases. The most common anti-microbial used for treatment was metronidazole (n=41), with complete resolution of symptoms and clearance of parasite occurring in 85% of cases. A treatment failure rate occurred in 15% of those treated with metronidazole. Follow-up treatment comprised of an additional course of metronidazole or iodoquinol was needed in order to achieve complete resolution of infection and symptoms in this group. This study demonstrates the pathogenic potential of D. fragilis in children and as such it is recommended that all laboratories must routinely test for this organism and treat if detected.

Clinical and laboratory findings in 220 children with recurrent abdominal pain.

AIM: To investigate the clinical and laboratory findings in children with recurrent abdominal pain (RAP). METHODS: Consecutive patients with RAP (Apley criteria), age 4-16 years, referred to a secondary medical centre were evaluated by a standardized history, physical examination and laboratory tests. The tests encompassed Helicobacter pylori (Hp), gastrointestinal bacterial infections, protozoa, coeliac disease, carbohydrate malabsorption, food intolerance, abdominal ultrasound and plain abdominal X-ray. More investigations were obtained if indicated. Patient characteristics were compared with surgical patients without abdominal pain (control group). RESULTS: A total of 220 consecutive patients were included (92 M, mean age 8.8 years [4.1-16.0 years]). In 88% of the patients, abnormalities were found that refer to possible causes. Especially, protozoa were present in 33% of the patients, mostly Dientamoeba fragilis, Yersinia enterocolitica in 12% and endoscopically proven infection with Hp in 11%. In 36%, a plain abdominal X-ray raised suspicion of constipation. CONCLUSION: In 220 consecutive patients with RAP, referred to secondary care, a standardized work-up yielded abnormal results in a high percentage. The clinical significance of these findings remains to be established.

Acute eosinophilic myocarditis: diagnosis and treatment.

Hypereosinophilic syndrome (HES) is a rare disorder of unregulated eosinophilia, which if untreated, may lead to systemic tissue infiltration and inflammation. Cardiac involvement is a common and serious associated complication. We describe a case of HES associated myocarditis mimicking a non-ST elevation MI (NSTEMI). Unlike myocarditis in general, our patient responded well to high dose methylprednisone, the standard of care in HES. We review the clinical presentation, pathophysiology, pathology and treatment of eosinophilic myocarditis related to HES.

Blastocystis: unravelling potential risk factors and clinical significance of a common but neglected parasite.

Two independent studies were conducted to describe symptoms and potential risk factors associated with Blastocystis infection. Isolates were subtyped by molecular analysis. In the NORMAT study (126 individuals randomly sampled from the general population) 24 (19%) were positive for Blastocystis. Blastocystis was associated with irritable bowel syndrome (P=0.04), contact with pigs (P<0.01) and poultry (P=0.03). In the Follow-up (FU) study (follow-up of 92 Blastocystis-positive patients), reports on bloating were associated with subtype (ST) 2 (P<0.01), and blood in stool to mixed subtype infection (P=0.06). ST1 was more common in FU individuals (32%) than in NORMAT individuals (8%), whereas single subtype infections due to ST3 or ST4 were seen in 63% of the NORMAT cases and 28% of the FU cases. Only FU individuals hosted ST7, and ST6/7 infections due to ST7 or ST9 were characterized by multiple intestinal symptoms. The data indicate subtype-dependent differences in the clinical significance of Blastocystis.

Transmission of Dientamoeba fragilis: evaluation of the role of Enterobius vermicularis.

The role of Enterobius vermicularis in the transmission of Dientamoeba fragilis has been evaluated in two groups of patients admitted to the Parasitology Laboratory of Celal Bayar University: one group with E. vermicularis infection (n=187, Pinworm Group), and the other with D. fragilis infection (n=126, Dientamoeba Group). The presence of the other parasite, pinworm or Dientamoeba, was investigated with the microscopic examination of cellophane tape and stool samples for three consecutive days. In the Pinworm Group, 9.6% of the patients were found to be coinfected with D. fragilis, while 25.4% of the patients in the Dientamoeba Group were found to be coinfected with pinworms. The coincidence rates of D. fragilis and E. vermicularis, higher than the prevalence of each parasite in similar populations, suggest a common relation between these two parasites, possibly in entering the human body. E. vermicularis infection was found to be significantly more common in younger children (p<0.001), indicating that younger children may also be at higher risk for D. fragilis infection. These findings also raise the question of whether the unrelated symptoms of the pinworm infected patients such as abdominal pain and diarrhea may actually be due to overlooked Dientamoeba infections.

Irritable bowel syndrome: a review on the role of intestinal protozoa and the importance of their detection and diagnosis.

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder in which abdominal pain is associated with a defect or a change in bowel habits. Gut inflammation is one of the proposed mechanisms of pathogenesis. Recent studies have described a possible role for protozoan parasites, such as Blastocystis hominis and Dientamoeba fragilis, in the etiology of IBS. Dientamoeba fragilis is known to cause IBS-like symptoms and has a propensity to cause chronic infections but its diagnosis relies on microscopy of stained smears, which many laboratories do not perform, thereby leading to the misdiagnosis of dientamoebiasis as IBS. The role of B. hominis as an etiological agent of IBS is inconclusive, due to contradictory reports and the controversial nature of B. hominis as a human pathogen. Although Entamoeba histolytica infections occur predominately in developing regions of the world, clinical diagnosis of amebiasis is often difficult because symptoms of patients with IBS may closely mimic those patients with non-dysenteric amoebic colitis. Clinical manifestations of Giardia intestinalis infection also vary from asymptomatic carriage to acute and chronic diarrhoea with abdominal pain. These IBS-like symptoms can be continuous, intermittent, sporadic or recurrent, sometimes lasting years without correct diagnosis. It is essential that all patients with IBS undergo routine parasitological investigations in order to rule out the presence of protozoan parasites as the causative agents of the clinical signs.

[Dientamoeba fragilis: possibly an important cause of persistent abdominal pain in children]. / Dientamoeba fragilis: een mogelijk belangrijke oorzaak van persisterende buikpijn bij kinderen.

OBJECTIVE: To determine the effect of an antiprotozoic treatment on children with persistent abdominal pain and infection with Dientamoeba fragilis. DESIGN: Retrospective. METHOD: A total of 43 children with D. fragilis infection and persistent gastrointestinal complaints were included in the study. Of these 27 were treated with clioquinol and 16 with a nitroimidazole drug: metronidazole or tinidazole. The parasitological and clinical effects of the treatment were assessed. RESULTS: In 33 of the 43 (77%) children, no parasites were detected during follow-up with a triple faeces test: 22/27 following treatment with clioquinol and 11/16 following treatment with a nitroimidazole drug. In 27 of the 33 (82%) children with a negative follow-up result, gastrointestinal complaints were considerably less or had completely disappeared. In 2 of the 10 (20%) children in which D. fragilis had not disappeared in the follow-up period, the complaints were less or had disappeared. CONCLUSION: Effective treatment of D. fragilis infection in children with longstanding gastrointestinal complaints often resulted in a reduction or disappearance of the complaints.

Dientamoeba fragilis infection presenting to the emergency department as acute appendicitis.

Dientamoeba fragilis is a non-enteroinvasive, protozoan parasite of the human large intestine with a worldwide prevalence. Considered for years to be a non-pathogenic organism, more recent studies suggest that up to 25% of adult hosts and up to 90% of infested children may manifest clinical disease. D. fragilis infestation has been implicated in chronic gastrointestinal syndromes characterized by protean complaints such as post-prandial abdominal pain, chronic diarrhea, flatulence, fatigue, anorexia, and weight loss. Rarely, D. fragilis infestation is the etiology of acute abdominal pain, mimicking a surgical abdomen. A case report is presented that details a patient with a 1-month history of vague abdominal complaints who presented to the Emergency Department with an apparent episode of acute appendicitis.

[Dientamoeba fragilis: pathogenic flagellate?]. / Dientamoeba fragilis: flagelle pathogène?

INTRODUCTION: D. fragilis is an intestinal protozoa whose pathogenic characteristics are increasingly recognized. The aim of this study is to specify the epidemiologic, biological and clinical aspects of this protozoa. MATERIAL USED AND METHODOLOGY: Survey conducted on 27,058 parasitological test of stools in parasitology-mycology laboratory of the Sfax University Hospital over a period of 5 years. RESULTS: 11,254 parasitological test of stools were positive (41.6%) of which 89.3% comprised protozoa. D. fragilis was found in 1497 cases (13.3% of the positive cases). In 65% of these cases, it was associated with other intestinal parasites in particular Blastocystis hominis (40.3%), Endolimax nanus (24%), Entamoeba coli (6%), Giardia intestinalis (5.7%) and Enterobius vermicularis (5%). Those patients having a parasitism with isolated D. fragilis were predominantly female and young subjects (< 20 years). Clinical signs included abdominal pain (88.5%), anorexia (50%), alternating diarrhoea and constipation (40.4%) and diarrhoea (21%) with mucus in 7.6%. DISCUSSION: D. fragilis is today classified in the group of flagellates and we share the opinion of the majority of the authors as to its real pathogenic capacity.

Blastocystis hominis: pathogen or fellow traveler?

Blastocystis hominis, an intestinal organism of uncertain taxonomic position, has long been considered nonpathogenic. Some recent studies suggest, however, that it may be associated with diarrhea and may respond to treatment with iodoquinol or metronidazole. To investigate this possibility, we identified 148 persons whose stools contained this organism. Of this number, 32 had at least 6 stool examinations performed. Twenty-seven of the 32 persons were later found to have greater than or equal to 1 recognized pathogens--Entamoeba histolytica, Giardia lamblia or Dientamoeba fragilis--and, after receiving appropriate therapy, became asymptomatic. The B hominis infection, however, was unaffected by therapy. Five persons with only B. hominis infection were treated with iodoquinol without effect; these persons fulfilled the medical criteria for irritable bowel syndrome. We believe that when an apparently symptomatic B. hominis infection responds to therapy, the improvement probably represents elimination of some other undetected organism causing the infection.

Dientamoeba fragilis: a review with notes on its epidemiology, pathogenicity, mode of transmission, and diagnosis.

Dientamoeba fragilis was found in 4.2% of approximately 43,000 individuals who submitted stools for parasitological examination during 1970 to 1974. The parasite was more frequently found in the younger age group (less than 20 years) than in older age groups, and more often in females than in males. Symptoms in 255 of patients in whom D. fragilis was the only parasite found and for whom detailed symptoms had been supplied, included: diarrhea, abdominal pains, anal pruritus, and loose stools. Analysis of mixed infections of D. fragilis with intestinal helminths suggests that such infections are random except for the combination of D. fragilis and Enterobius vermicularis. This combination occurred 9 times more often than theoretically expected. Daily periodicity and distribution of D. fragilis within stools of one patient were studied over a period of 6 months. More than twice as many organisms per ml of stool were present in the last than in the first portion evacuated. The total number of organisms excreted fluctuated markedly from day to day.