Prediction and attenuation of seasonal spillover of parasites between wild and domestic ungulates in an arid mixed-use system.

Transmission of parasites between host species affects host population dynamics, interspecific competition, and ecosystem structure and function. In areas where wild and domestic herbivores share grazing land, management of parasites in livestock may affect or be affected by sympatric wildlife due to cross-species transmission.We develop a novel method for simulating transmission potential based on both biotic and abiotic factors in a semi-arid system in Botswana. Optimal timing of antiparasitic treatment in livestock is then compared under a variety of alternative host scenarios, including seasonally migrating wild hosts.In this region, rainfall is the primary driver of seasonality of transmission, but wildlife migration leads to spatial differences in the effectiveness of treatment in domestic animals. Additionally, competent migratory wildlife hosts move parasites across the landscape.Simulated transmission potential matches observed patterns of clinical disease in livestock in the study area. Increased wildlife contact is correlated with a decrease in disease, suggesting that non-competent wild hosts may attenuate transmission by removing infective parasite larvae from livestock pasture.Optimising the timing of treatment according to within-year rainfall patterns was considerably more effective than treating at a standard time of year. By targeting treatment in this way, efficient control can be achieved, mitigating parasite spillover from wildlife where it does occur. Synthesis and applications. This model of parasite transmission potential enables evidence-based management of parasite spillover between wild and domestic species in a spatio-temporally dynamic system. It can be applied in other mixed-use systems to mitigate parasite transmission under altered climate scenarios or changes in host ranges.

Clinical and Immunologic Features of Ultra-Short Celiac Disease.

BACKGROUND & AIMS: The clinical effects of gluten-sensitive enteropathy with villous atrophy limited to the duodenal bulb (D1) have not been delineated in adults with celiac disease. We investigated the sensitivity of D1 biopsy analysis in the detection of celiac disease, the number and sites of biopsies required to detect ultra-short celiac disease (USCD, villous atrophy limited to D1), and the clinical phenotype of USCD. METHODS: We performed a prospective study of 1378 patients (mean age, 50.3 y; 62% female) who underwent endoscopy at a tertiary medical center in the United Kingdom from 2008 through 2014; routine duodenal biopsy specimens were collected from D1 and the second part of the duodenum (D2). Quadrantic D1 biopsy specimens were collected from 171 consecutive patients with a high suspicion of celiac disease (mean age, 46.5 y; 64% female). Clinical data from patients diagnosed with USCD, based on biopsy analysis, were compared with those from patients with conventional celiac disease (CCD) (villous atrophy beyond D1) and individuals without celiac disease (controls). The number of intraepithelial lymphocytes (IELs) and immune phenotypes were compared between D1 vs D2 in patients with celiac disease. RESULTS: Of the 1378 patients assessed, 268 (19.4%) were diagnosed with celiac disease; 9.7% of these patients had villous atrophy confined to D1 (USCD; P < .0001). Collection of a single additional biopsy specimen from any D1 site increased the sensitivity of celiac disease detection by 9.3%-10.8% (P < .0001). Patients with USCD were younger (P = .03), had lower titers of tissue transglutaminase antibody (P = .001), and less frequently presented with diarrhea (P = .001) than patients with CCD. Higher proportions of patients with CCD had ferritin deficiency (P = .007) or folate deficiency (P = .003) than patients with USCD or controls. Patients with celiac disease had a median of 50 IELs/100 enterocytes in D1 and a median of 48 IELs/100 enterocytes (P = .7) in D2. The phenotype of IELs from patients with D1 celiac disease was indistinguishable from those of patients with D2 celiac disease. CONCLUSIONS: Collection of a single additional biopsy specimen from any site in the D1 intestine increases the sensitivity of detection for celiac disease. Patients with USCD may have early stage or limited celiac disease, with a mild clinical phenotype and infrequent nutritional deficiencies.

Gastro-oesophageal reflux symptoms and coeliac disease: no role for routine duodenal biopsy.

BACKGROUND: Coeliac disease (CD) has been linked to gastro-oesophageal reflux disease (GORD). Previous studies have demonstrated an increased prevalence of reflux in patients with CD. However data on the risk for CD in patients presenting with reflux are conflicting. AIMS: The aim of this study was to establish the prevalence of CD in patients with GORD and to elucidate the mechanisms for reflux symptoms in newly diagnosed CD patients. METHODS: Group A: patients who had undergone routine duodenal biopsy were prospectively recruited between 2004 and 2014. Diagnostic yield was compared with that of a screening cohort. Group B: 32 patients with newly diagnosed CD who had undergone oesophageal manometry and 24-h pH studies were prospectively recruited. RESULTS: Group A: 3368 patients (58.7% female, mean age 53.4 years) underwent routine duodenal biopsy. Of these patients, 850 (25.2%) presented with GORD. The prevalence of CD among GORD patients was 1.3% (0.7-2.4%), which was not significantly higher than that in the general population (P=0.53). Within the context of routine duodenal biopsy at endoscopy (when corrected for concurrent symptoms, age and sex), reflux was found to be negatively associated with CD [adjusted odds ratio 0.12 (0.07-0.23), P<0.0001]. In group B, 34% of patients complained of reflux. On manometry, 9% had a hypotensive lower oesophageal sphincter and 40.6% had oesophageal motor abnormalities, with 25% significantly hypocontractile. On pH studies, 33% demonstrated reflux episodes. CONCLUSION: The prevalence of undiagnosed CD among GORD patients is similar to that in the general population, and routine duodenal biopsy cannot be recommended. A significant number of patients with newly diagnosed CD were found to have reflux and/or oesophageal dysmotility on pH/manometry studies; this may explain the high prevalence of reflux symptoms in CD.

Point-of-care testing for celiac disease has a low sensitivity in endoscopy.

BACKGROUND: Celiac disease (CD) is a common but underdiagnosed condition. A rapid point-of-care test (POCT) could reduce lead times and missed diagnoses. OBJECTIVE: To assess the utility of an immunoglobulin (Ig) A tissue transglutaminase (TTG) antibody POCT in an endoscopic setting. DESIGN: Prospective observational study. SETTING: A single UK university hospital. PATIENTS: Patients presenting with suspected CD, known CD, and routine endoscopy for upper GI symptoms. INTERVENTIONS: All patients were tested with POCT, serum TTG, endomysial antibody (EMA), and upper GI endoscopy with duodenal biopsies at the same visit. MAIN OUTCOME MEASUREMENTS: Comparison was made with histology in all cases, with villous atrophy regarded as diagnostic of CD. RESULTS: A total of 576 patients (63.5% female, mean [± standard deviation] age 49.7 years [± 17.6 years]) were recruited. A total of 523 patients had no prior diagnosis of CD, and 53 patients had known CD coming for reassessment. A total of 117 patients were newly diagnosed with CD, and 82 were positively identified by the POCT. Sensitivity, specificity, positive predictive value, and negative predictive value were 70.1%, 96.6%, 85.4%, and 91.8%, respectively. In comparison, TTG and EMA both performed significantly better than the POCT. Sensitivity and specificity of TTG were 91.0% and 83.5%, respectively, and EMA were 83.8% and 97.5%, respectively. Of patients with known CD coming for reassessment, 26 had villous atrophy, and POCT results were positive in 16 (61.5%). There was poor agreement between POCT and standard serology. LIMITATIONS: High pre-test probability of CD. CONCLUSION: The performance of this POCT was disappointing compared with standard serology and cannot at present be recommended within the context of an endoscopy unit.

Case-finding for coeliac disease in secondary care: a prospective multicentre UK study.

BACKGROUND: Coeliac disease affects 1% of the population. Despite this high prevalence, the majority of individuals are undetected. Many patients present with subtle symptoms which may also contribute to under diagnosis. Our aim was to determine the relative importance of different presenting characteristics. METHODS: Unselected gastroenterology patients referred to 4 hospitals in South Yorkshire were investigated for coeliac disease. Diagnosis was based on positive serology and the presence of villous atrophy. Odds ratios were calculated for presenting characteristics and multivariate analysis performed to identify independent risk factors. RESULTS: 4089 patients were assessed (41.5% male, mean age 55.8 ± 18.2 years); 129 had coeliac disease (3.2%, 95% CI 2.6-3.7%). Multivariate analysis of patients referred to secondary care showed family history of coeliac disease (OR 1.26, p < 0.0001), anaemia (OR 1.03, p < 0.0001) and osteoporosis (OR 1.1, p = 0.006) were independent risk factors for diagnosis of coeliac disease. When compared to population controls, diarrhoea (OR 4.1, p < 0.0001), weight loss (OR 2.7, p = 0.02), irritable bowel syndrome symptoms (OR 3.2, p = 0.005) thyroid disease (OR 4.4, p = 0.01) and diabetes (OR 3.0, p = 0.05) were also associated with increased coeliac disease risk. CONCLUSIONS: Coeliac disease accounts for 1 in 31 referrals in secondary care to unselected gastroenterology clinics. A low threshold for coeliac disease testing should be adopted.

Capsule endoscopy in adult celiac disease: a potential role in equivocal cases of celiac disease?

BACKGROUND: There have been limited studies evaluating capsule endoscopy (CE) in equivocal celiac disease (CD). OBJECTIVE: To determine the role CE may have in equivocal CD cases, compared with patients with biopsy-proven and serology-proven CD who have persisting symptoms. DESIGN: Prospective cohort study. SETTING: University hospital. PATIENTS: A total of 62 patients with equivocal CD and 69 patients with nonresponsive CD. INTERVENTION: CE. MAIN OUTCOME MEASUREMENTS: Diagnostic yield of CE in equivocal cases and accuracy of mucosal abnormality detection in patients with nonresponsive CD. RESULTS: Equivocal cases (n = 62) were divided into two subgroups: group A (antibody-negative villous atrophy, n = 32) and group B (Marsh 1-2 changes, n = 30). In group A, CE secured a diagnosis of CD or Crohn's disease in 28% (9/32), significantly higher than the diagnostic yield in group B (7%; P = .044). In patients with CD with persisting symptoms, significant CE findings were identified in 12% (8/69), including 2 cases of enteropathy-associated lymphoma, 4 type 1 refractory disease cases, 1 polypoidal mass histologically confirmed to be a fibroepithelial polyp, and 1 case of ulcerative jejunitis. This outcome was significantly lower than the diagnostic yield of CE in antibody-negative villous atrophy (P = .048). LIMITATIONS: Single center. CONCLUSION: There have been no previous reports systematically evaluating equivocal CD by using CE. The diagnostic yield of CE in patients with antibody-negative villous atrophy is better than that of CE in patients with CD with persisting symptoms. We advocate the use of CE in equivocal cases, particularly in patients with antibody-negative villous atrophy.

Celiac disease.

Celiac disease is common, affecting approximately 1 in 100 people, yet it remains underdiagnosed. This article reviews our current understanding of celiac disease, diagnosis, and common pitfalls. Although the cornerstone of treatment is a gluten-free diet, some patients may still have persisting symptoms and warrant further investigations.

Treatment failure in coeliac disease: a practical guide to investigation and treatment of non-responsive and refractory coeliac disease.

Coeliac disease is a common condition affecting up to 1% of the European adult population. Whilst the majority of patients will respond to a gluten free diet with resolution of symptoms and an improvement in histology, a significant minority have persistent problems. Refractory coeliac disease is a relatively uncommon cause of non-response to gluten free diet with potentially serious consequences of severe malabsorption and a high rate of progression to lymphoma. This review provides a practical guide to the investigation of patients who do not respond to a gluten free diet. We will highlight the differences between the more common non-responsive coeliac disease and the rare entity of refractory coeliac disease and discuss current management and treatment options for both non-responsive coeliac disease and refractory coeliac disease.

Duodenal bulb biopsies for diagnosing adult celiac disease: is there an optimal biopsy site?

BACKGROUND: Recent studies highlight the role of duodenal bulb biopsy in the diagnosis of celiac disease. OBJECTIVE: To determine whether a targeted duodenal bulb biopsy in addition to distal duodenal biopsies is the optimal strategy to identify villous atrophy. DESIGN: Prospective cohort study. SETTING: Tertiary-care referral center. PATIENTS: Seventy-seven patients undergoing clinically indicated EGD with duodenal biopsies were recruited. Of these, 28 had newly diagnosed celiac disease and 49 were controls. INTERVENTIONS: At endoscopy, 8 duodenal biopsy specimens were taken: 4 from the second part of the duodenum and 4 quadrantically from the bulb (at the 3-, 6-, 9-, and 12-o'clock positions). MAIN OUTCOME MEASUREMENTS: Increasing the diagnostic yield and detection of the most severe villous atrophy in celiac disease with the addition of a targeted duodenal bulb biopsy. RESULTS: The most severe degree of villous atrophy was detected when distal duodenal biopsy specimens were taken in addition to a duodenal bulb biopsy specimen from either the 9- or 12-o'clock position (96.4% sensitivity; 95% CI, 79.7%-100%). The difference between the 12-o'clock position biopsy and the 3-o'clock position biopsy in detecting the most severe villous atrophy was 92% (24/26) versus 65% (17/26) (P = .02). LIMITATIONS: Small sample and study performed in a tertiary referral center. CONCLUSIONS: This study demonstrates the patchy appearance of villous atrophy that occurs within the duodenum. A targeted duodenal bulb biopsy from either the 9- or 12-o'clock position in addition to distal duodenal biopsies may improve diagnostic yields by detecting the most severe villous atrophy within the duodenum.

A prospective study of duodenal bulb biopsy in newly diagnosed and established adult celiac disease.

OBJECTIVES: Recent reports suggest that the duodenal bulb may be the only site to demonstrate villous atrophy (VA) in celiac disease. However, there is a paucity of data from newly diagnosed adult celiac patients and no data from those patients with established celiac disease. The objective of this study was to compare the histological findings in the duodenal bulb and distal duodenum of patients with adult celiac disease (newly diagnosed or established) against controls. METHODS: A total of 461 patients were prospectively recruited. Biopsies were graded using the Marsh criteria. RESULTS: In all, 461 patients (300 females and 161 males) with median age 51 years were analyzed. In all, 126 had newly diagnosed celiac disease, 85 established celiac disease, and 250 controls. New diagnosis celiac disease (9%, P<0.0001) and established celiac disease (14%, P<0.0001) were more likely than controls to have VA in the bulb alone. Overall, when comparing the histological lesion of the bulb against the distal duodenum, 31/85 with established celiac disease (P<0.0001) and 21/126 newly diagnosed (P=0.0067) had a discrepancy in the severity of the lesion between the two sites compared with 18/250 controls. In all, 24/31 with established celiac disease and 16/21 newly diagnosed had the more severe lesion in the bulb. CONCLUSIONS: VA may be present only in the duodenal bulb. This study suggests that the optimal assessment of patients in whom celiac disease is suspected (with positive serology) and those with established celiac disease requires a duodenal bulb biopsy in addition to distal duodenal biopsies.

Bile acid malabsorption: an under-investigated differential diagnosis in patients presenting with diarrhea predominant irritable bowel syndrome type symptoms.

OBJECTIVE: Bile acid malabsorption (BAM) has been reported as a possible cause of diarrhea predominant irritable bowel syndrome (D-IBS) type symptoms. We aimed to determine how commonly patients with D-IBS type symptoms had a diagnosis of BAM as demonstrated by a positive SeHCAT (75 Selenium-homocholic acid taurine) test (retention <10% at seven days). MATERIALS AND METHODS: A retrospective analysis was undertaken of patient's records for all patients who underwent a SeHCAT test between 2001 and 2009 in a tertiary hospital (Group A). Concurrently, a cohort of patients with Rome II D-IBS type symptoms was examined to determine the potential utility of SeHCAT test (Group B). RESULTS: In Group A 39.2% (n = 107/273) of patients had a positive SeHCAT result. The median time from first hospital visit to SeHCAT result was 30 weeks. Predictive factors for BAM: terminal ileal Crohn's disease (p < 0.01), terminal ileal resection (p < 0.01), and previous cholecystectomy (p < 0.01). 33.6% of patients who had a positive SeHCAT also had Rome II D-IBS. In Group B the D-IBS control cohort only 1.9% of patients had undergone a SeHCAT scan (p < 0.001 compared to Group A). CONCLUSION: BAM is common and should be considered earlier when investigating unselected patients with D-IBS type symptoms.

Are patients with coeliac disease seeking alternative therapies to a gluten-free diet?

BACKGROUND & AIMS: The cornerstone of treatment for coeliac disease is a gluten-free diet (GFD). However, adherence to a GFD is variable. Recently investigators have been reporting their preliminary findings using novel therapies. In addition, there is a growing interest in the use of complementary or alternative medicine (CAM) in gastrointestinal illnesses. These observations suggest that patients with coeliac disease may be dissatisfied with a GFD and possibly are seeking/using alternative therapies for their disease. Our aim was to assess the satisfaction levels of adults with coeliac disease towards a GFD, their use of oral CAM and views regarding novel therapies. METHODS: 310 patients with coeliac disease completed a questionnaire survey while attending their out-patient appointment. The control group comprised 477 individuals. RESULTS: Over 40% of patients with coeliac disease were dissatisfied with a GFD. The frequency of CAM use in patients with coeliac disease was 21.6% (67/310) vs 27% in the control group (129/477), p=0.09. All patients expressed an interest in novel therapies, with a vaccine being the first choice in 42% of patients, 35% and 23% for anti- zonulin and peptidases, respectively. Universally, patients placed genetically modified wheat as the lowest preference. CONCLUSIONS: A large proportion of patients with coeliac disease are dissatisfied with a GFD. Coeliac patients are not taking CAM any more than controls, suggesting they do not view CAM as an alternative to a GFD. However, all the patients in this survey were keen to consider novel therapies, with a vaccine being the most preferred option.

Pancreatic insufficiency in adult celiac disease: do patients require long-term enzyme supplementation?

BACKGROUND: Celiac disease is associated with exocrine pancreatic insufficiency. We previously reported that in 30% (20/66) of adult celiac patients with current or persistent diarrhea the underlying cause was exocrine pancreatic insufficiency. Of these 20 patients, 19 initially improved on pancreatic supplementation. To date, there are no published longitudinal studies. METHODS: The 20 patients who had initially received therapy for exocrine pancreatic insufficiency were prospectively followed-up for 4 years. Gastrointestinal symptoms, dietary adherence, celiac antibody status, and dose of enzyme supplementation were recorded. Fecal elastase-1 (Fel-1) was repeated to reassess exocrine pancreatic function. RESULTS: In the study, 19/20 patients were reviewed, as one had died (mean age 59.7 years, 7 males). The mean duration of celiac disease was 13.2 years. Eleven out of nineteen were still taking enzyme supplementation at a mean dose of 45,000 units of lipase per day. Only 1/11 reported no symptomatic benefit and 8/19 patients had discontinued supplementation because their diarrhea had improved. In the whole group there was a significant increase in Fel-1 levels over time, with median values of 90 µg/g at 0 months, 212 µg/g at 6 months, and 365 µg/g at follow-up (45-66 months)(p < 0.0001). CONCLUSIONS: Fecal elastase-1 is useful in identifying exocrine pancreatic insufficiency in adult celiac patients with diarrhea. Our longitudinal data suggests that pancreatic enzyme supplementation could be discontinued in a substantial proportion of patients as symptoms improve.

Be vigilant for patients with coeliac disease.

Recent population studies show that coeliac disease affects around 1 in 100 people. The estimated ratio of diagnosed to undiagnosed individuals is 1:8, and the average delay in diagnosis is reported to be 11 years. The contemporary coeliac patient is diagnosed between the ages of 40 and 60, has normal or even high BMI, and subtle symptoms. Patients are often identified in screening groups which would include those with type 1 diabetes, autoimmune thyroid disease, or a first-degree relative with coeliac disease. The presence of relevant symptoms is not essential for a diagnosis of coeliac disease. Additionally, positive serological testing alone is not sufficient to confirm the diagnosis. Endomysial antibody (EMA) and tissue transglutaminase (TTG) have a combined sensitivity and specificity of > 90% when used in combination in selected populations. However, false positives occur in conditions such as inflammatory bowel disease, and autoimmune disease. Conversely antibody-negative disease accounts for around 9% of cases. IgA deficiency is a cause of false negatives and levels should be checked at the same time as EMA and TTG. Patients must consume a gluten-containing diet for six weeks before serological testing and biopsy if necessary. All those with positive serological tests, and those for whom clinical suspicion is high even if seronegative, should be referred to a gastroenterologist for a duodenal biopsy to confirm or exclude coeliac disease. Diagnosis requires the demonstration of villous atrophy in the small bowel which improves when gluten is withdrawn.

Joint BAPEN and British Society of Gastroenterology Symposium on 'Coeliac disease: basics and controversies'. Coeliac disease: optimising the management of patients with persisting symptoms?

The vast majority of patients with coeliac disease will derive benefit from a gluten-free diet. However, some patients will not improve on the gluten-free diet or they will have a relapse of their symptoms. The present review will focus on this group of patients. Definitions for non-responsive coeliac disease and refractory coeliac disease will be provided. The most common reason for recurrent symptoms is continued gluten exposure. Other causes of persisting symptoms are discussed, including alternative causes of villous atrophy or co-existent pathology. Current literature is reviewed, including an initial investigation strategy for patients with persisting symptoms. A pragmatic management plan is described that can be initiated by any clinician. Finally, the current optimal investigational pathway for patients with refractory (or suspected refractory) coeliac disease is discussed and the reported effects of a number of therapeutic options are summarised. The aim of the present article is to provide clinicians with an up-to-date review of the literature in this clinical field and allow them to determine the most appropriate management strategy.