eCommons@AKU

Section of Department of Medicine

May 2010 Emerging Parasitic Infection Mimicking Functional Bowel Disease javed Yakoob Aga Khan University, [email protected]

Wasim Jafri Aga Khan University, [email protected]

Mohammad Asim Beg Aga Khan University

Z Abbas Aga Khan University, [email protected] shagufta Naz, Aga Khan University

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Recommended Citation Yakoob, j., Jafri, W., Beg, M. A., Abbas, Z., Naz,, s., Islam, M., Khalid, A., Khan, R., Ahmad, Z. (2010). Emerging Parasitic Infection Mimicking Functional Bowel Disease. Gastroenterology, 138(5 (supplement 1)), S-587-S-588. Available at: http://ecommons.aku.edu/pakistan_fhs_mc_med_gastroenterol/118 Authors javed Yakoob; Wasim Jafri; Mohammad Asim Beg; Z Abbas; shagufta Naz,; Muhammad Islam; A. B. Khalid; Rustam Khan; and Zubair Ahmad

This article is available at eCommons@AKU: http://ecommons.aku.edu/pakistan_fhs_mc_med_gastroenterol/118 complex containing both protein and RNA molecules (i.e., a ribonucleoprotein complex) T1828 and small nuclear ribonuclear polypeptide A were present in high titers in serum that contained anti-enteric neuronal antibodies in our neuronal assays. Our Invitrogen®ProtoAr- Fructose and : Association With Atopy and Extra-GI ray assay did not find these antibodies in serum in which our immunostaining assay found Symptoms no anti-enteric neuronal antibodies. Moderate levels of anti-ro 52000 MW antibody were Clive H. Wilder-Smith, Andrea Materna present also in IBS serum. Anti-ro 52000 is a known biomarker for Sjögren's syndrome. INTRODUCTION: Sugar intolerances are common in patients with functional bowel dis- Conclusion: The gut does not work well when the enteric nervous system (ENS) is not orders (FBD), although the prevalence of sugar in not dissimilar to that in working well. The gut does not work at all without the ENS. The results suggest that healthy populations. The association of lactose and fructose intolerances with other food symptoms in an unexpectedly large subset of patients with a diagnosis of IBS, might result reactions, including allergies and pseudoallergies, as well as extra-gastrointestinal symptoms from a degenerative ENS neuropathy with anti-enteric antibodies serving as a biomarker. is unclear and would suggest additional disorders, such as increased intestinal permeability and immune activation. METHODS: We prospectively assessed the prevalence of fructose (50g) and lactose (50g) intolerance in 586 Caucasian secondary to tertiary care FBD patients T1826 (mean age: 42±16y, 431 females, Rome III criteria ) with H2 and CH4 breath testing (5 hours) as well as atopy and extra-GI symptoms using detailed questionnaires (during testing Altered Migrating Motor Complex After Side-to-Side Ileal Bypass in Mouse

and long-term). RESULTS: The prevalence of intolerance in these FBD patients was 76% AGA Abstracts : Physiologic Mechanism Underlying the Blind Loop Syndrome? for fructose and 56% for lactose. Respective times to peak symptoms were 110±63 and Suk-Bae Moon, Kyu Joo Park, Jung Sun Moon, Eun-Kyung Choe, In-Suk So, Sung-Eun 134±123 minutes. The commonest non-GI symptoms during testing with fructose/lactose Jung were tiredness (46%/72%), headache (34%/52%), diminished concentration (26%/40%), Introduction: Considering that MMC is a key element in intestinal motility, alterations in myalgia (14%/20%), arthralgia (14%/20%), rash (5%/9%) and cardiac arrhythmia (4%/5%). the MMC may be responsible for blind loop syndrome, a well-known complication following The long-term history in fructose/lactose intolerance revealed prevalences of eczema (26%/ side-to-side intestinal anastomosis. This study intended to investigate the physiological 9%), allergic rhinitis (19%/5%), asthma (12%/8%), oral allergy syndrome (14%/2%), hayfever mechanism underlying blind loop syndrome, based on migrating motor complex (MMC) (15%/5%), arthralgia (22%/8%), myalgia (18%/7%), tiredness (46%/19%), depression (19%/ in mouse model. Materials and Methods: Ileal side-to-side bypass anastomosis was performed 6%), drug allergies (10%/5%), reactions to cosmetics (12%/4%), reactions to household on female ICR mice. In partial bypass model, contents were allowed to enter both the cleaning agents (7%/2%) and a childhood history of atopy (19%/5%); ANOVA fructose bypassed segment and distally past the bypassed loop. In total bypass model, proximal versus lactose: p<0.01. Adverse reactions to foods other than fructose, lactose, other oligosac- portion of the bypass segment was doubly ligated, not allowing the contents to enter bypassed charides and polyols (FODMAPS) were reported in 27% of fructose intolerant and 9% of loop directly. After 2 weeks or 4 weeks of the operation, the ileum containing the bypass lactose intolerant (p<0.01). CONCLUSIONS: Significant non-GI symptoms were provoked loop was harvested and MMCs were recorded at 4 different recording channels (2 at the during sugar intolerance testing. Intolerant patients with FBD have a marked history of bypassed segment, and proximal and distal to the bypassed loop) with conventional tension atopy and non-GI adverse reactions. The significantly increased long-term prevalence of recordings in a organ bath continuously perfused with prewarmed (37.0±0.5°C) Krebs- atopy and non-GI symptoms in fructose intolerance suggests the involvement of increased Ringer buffer. Amplitude, duration, interval, propagation pattern, and area under the curve intestinal permeability and/or immune activation requiring further study. (AUC) of MMCs were measured and compared to the control. Results: In control intact mouse ileum (N=7), most MMCs propagated aborally (91.1%). After 2 weeks of partial bypass (N=4), the proportion of orally-propagating MMCs was significantly increased (p= T1829 .002) in the bypassed segment. Bidirectional MMCs were also observed (10%). After 4 weeks of partial bypass (N=4), the propagation direction did not change significantly (p=.422), as Effect of Traditional Japanese Medicine Daikenchuto (TJ-100) in Patients With compared to that of 2 weeks after the bypass. Amplitude and AUC of the MMCs decreased Chronic significantly after 2 weeks of partial bypass; the decrease of the amplitude became more Akira Horiuchi, Yoshiko Nakayama prominent at 4 weeks but the AUC showed no significant changes compared to that of 2 Objective: In Japan a traditional herbal medicine Daikenchuto (TJ-100) has been commonly weeks. In total bypass model at 2 weeks (N=6), bypassed segment had independent MMCs used for uncomfortable abdominal symptoms in patients with and not coordinated to the proximal segment. All of MMCs within the loop propagated aborally. chronic constipation. This study was to compare the effect of a stimulant laxative alone and After 4 weeks of total bypass (N=5), MMCs within the bypassed loop lost temporal relation- in combination with TJ-100 in improving stool frequency and in alleviating bloating and ship or completely disappeared. Amplitude and AUC of the MMCs decreased significantly abdominal pain in patients with chronic constipation. Patients and methods: All subjects in total bypass model, both at 2- and 4 weeks compared to the control state. Conclusions: who were enrolled in this study fulfilled the following; 1) they were taking a stimulant Continuation of intact intestinal tract seems to be required to maintain the amplitude and laxative, 24-60 mg/day of sennosides for at least three months, 2) they had abdominal AUC of the MMCs. Changes in the propagation direction of the MMCs and resultant symptoms including bloating and abdominal pain, 3) without the laxatives, the bowel stagnation of contents in the bypassed loop may be responsible for the development of blind movements were less than 3 times per week, 4) colonoscopy was normal, and 5) they had loop syndrome in partial bypass. Since the direction of propagation of the MMCs was no history of abdominal surgery. The study period was 12 weeks and consisted of 4 weeks maintained in total bypass, blind loop syndrome may be prevented. (pretreatment phase) before the administration of TJ-100, 6 weeks (treatment phase) for the administration of TJ-100, and 2 weeks (washout period) after cessation of TJ-100. The dose of TJ-100 used in this study is either 7.5 g/day or 15 g/day. The bowel movement T1827 frequency and the dose of sennoside required were recorded. Both bloating and abdominal pain were evaluated using visual analogue scale score. Abdominal symptoms were evaluated Neurogenic Bowel in Persons With Spinal Cord Injury: An Evaluation Using on the Gastrointestinal Symptoms Rating Scale. The gas volume score was measured at 0 SmartPill® Technology week and 6 week using the method described by Koide et al (Am J Gastroenterol 2000; Robert E. Williams, Ravi R. Vinnakota, Rany Z. Farid, Nishant Dhungel, Marinella D. 95:1735-41). Results: The addition of TJ-100 to sennoside resulted in significant improve- Galea, Truptesh H. Kothari, Ann M. Spungen, William Bauman, Mark A. Korsten ment in bloating (P<0.01) and abdominal pain (P<0.05). Its effects for abdominal pain were Background: Neurogenic bowel is common after spinal cord injury (SCI) and has been dose-dependent. There was no significant change in frequency of bowel movements or the associated with multiple secondary conditions, including difficulty with evacuation, impac- dose of sennoside used. The gas volume score was significantly decreased after the addition tion, and incontinence. Neurogenic bowel appears to prolong colonic transit time (CTT), of TJ-100 (P <0.05). Conclusions: The addition of TJ-100 reduced bloating and abdominal based on radiopaque marker studies. A relatively new device, the SmartPill®, is a small, pain in patients with chronic constipation receiving stimulant laxatives, possibly by decreasing wireless, ingestible capsule that offers the ability to assess temperature, pressure, pH, and the bowel gas volume. transit time as it traverses the gastrointestinal (GI) tract. The capsule measures these para- meters with an accuracy of +/- 1 degree C, +/- 5 mmHg, and +/- 0.5 pH units. CTT was determined in able-bodied subjects (AB) and those with SCI using the SmartPill® GI T1830 monitoring system. Methods: SCI-, and age-, and gender-matched AB control subjects were recruited. Following an 8 hour overnight fast, subjects consumed a standard test meal Emerging Parasitic Infection Mimicking Functional Bowel Disease consisting of 120g EggBeaters® [equivalent to 2 large eggs (60 kcals)], 2 slices of white Javed Yakoob, Wasim Jafri, Mohammad Asim Beg, Zaigham Abbas, Shagufta Naz, bread (120 kcal), and 30g strawberry jam (74 kcal). A pH calibrated SmartPill® capsule Muhammad Islam, Abdullah B. Khalid, Rustam Khan, Zubair Ahmad was ingested with 8 ounces of water. Subjects were provided with a portable data receiver Background: Irritable bowel syndrome (IBS) is a functional bowel disorder characterized by and remained fasted for 6 hours following capsule ingestion, at which time they consumed abdominal pain and changes in bowel habits. The common symptoms include lower abdom- 1 Ensure Plus® nutrition shake (350 kcal). Subjects remained fasted for an additional 2 inal pain and bloating with alteration of bowel habits that may be described as hours, after which time they resumed their normal diets. Data was collected by the data (IBS-D). Microsporidial infections are important infection in immunocompromized patients. receiver until the capsule was excreted. CTT was defined as the time elapsed between the These parasites are easily detected by light microscopy when infections are heavy however, second abrupt increase in pH (indicating entry to the cecum) and an abrupt decrease in early infections without spores, or light infections with low numbers of spores, are easily temperature (indicating excretion). Results: Data are expressed as mean +/- SD. Ten subjects missed. This study was designed to determine the prevalence of Microsporidial infection in with paraplegia (PARA) (8 males, 2 females; age, 55 +/- 12 years; duration of injury, 16 +/- patients with IBS-D and compare it with those with out IBS-D. Methodology: Three hundred 14 years; level of injury, T4-L2), 6 subjects with tetraplegia (TETRA) (6 males; age, 44 +/- and one patients with 202(67%) were males with a mean age of 41±15 years and range 15- 21 years; duration of injury, 11 +/- 7 years; level of injury C4-C7), and 8 AB subjects (6 83 years were enrolled from January 2007 - December 2009 at the gastroenterology outpatient males, 2 females; age, 43 +/- 11 years) were recruited for study. CTT was significantly longer clinic of the Aga Khan University Hospital, Karachi. Patients underwent history, physical in PARA compared to the AB group (51.8 +/- 47.0 vs. 13.6 +/- 8.4 hours, p<0.05). The and laboratory examination including stool microscopy with wet mount, Trichrome staining TETRA group trended to have a longer CTT compared to the AB group (p=0.09). Total and polymerase chain reaction (PCR) for microsporidia. Stool DNA was extracted using colonic mean peak amplitude (MPA) was significantly lower in the PARA and TETRA groups Qiagen Stool DNA extraction kit. The primers used for PCR were previously described in compared to the AB group (16.7 +/- 6.0 and 12.2 +/- 5.5 vs. 25.5 +/- 6.5 mmHg, respectively, literature. Rome III criteria was used to define patients with IBS-D and epigastric pain p<0.01). Conclusion: In agreement with previous marker studies, CTT was prolonged in syndrome. Comparison between groups was assessed using the chi-squared test, Fischer's PARA. MPA was reduced in both PARA and TETRA groups. These findings may result from exact test or likelihood ratio whichever appropriate. All p-value less than 0.05 was considered decreased parasympathetic tone to the colon and may be responsible, in part, for the statistical significant. Result: One hundred-forty (47%) were diagnosed as IBS-D, 138(46%) secondary consequences of neurogenic bowel. had epigastric pain syndrome and 23(7%) had C (HCV)-related chronic liver

S-587 AGA Abstracts AGA Abstracts ept nraigeiec uprigterl fti rtza ndgsiedisorders. digestive in protozoan this controversial of is BH role of the pathogenicity the supporting However, popula- evidence organism. the of this increasing 11-38% with indicate despite infected Europe be and States may United tion the from studies Surveillance tract. Purpose: Stuppy P. William Nitazoxanide With Eradication hominis Blastocystis T1833 of 4 appears since smithii. examined smithii M. be detectable Methanobrevibacteri also no must C-IBS. had methanogens subjects with other methane although subjects 9 subjects methane these appear in in flavifaciens important and uncommon not at albus although be methane Ruminococcus (118±53ppm) Conclusions: for to smithii significant. area-under-the-curve be M. greater to methane without enough a only subjects powered Among had methane subjects. to smithii non-methane compared M. (20%) produ- 187±85ppm 10 for methane of positive Flavifaciens. (56%) 2 R. those 9 in and of producers, positive albus 5 weakly R. in only The both present and of groups. strongly cers evidence was had between smithii 156±77ppm. positive) was Methanobrevibacter different (methane test However, patient breath not 1 of only minutes were in PCR 120 first the pain On constipation for the In -0.11±3.6 for significant abdominal area-under-the-curve to groups. towards and methane mean compared between balance Bloating 5.1±3.8 the different subjects. was indicating After no methane score (P<0.01) Results: was C-D subjects stool symptom age without female) non-methane validated in average (8 the subjects The presence group 10 study. their and methane with the detect female) (8 completed to subjects methane used 9 applied were were criteria rRNA exclusion 16S Rumin- and testing. flavifaciens albus previously Ruminococcus breath with ococcus smithii, PCR sample. on Methanobrevirbacter QIAamp). stool for (Qiagen methane frozen specific extracted fresh methane primers was for a published DNA provide with bacterial positive to sample, asked not stool subjects were each IBS subjects From results, testing, with were breath determined. test of subjects were completion testing IBS included breath After predominant breath group constipation and and control lactulose questionnaire testing) The of for a minutes are presenting 180 Using test during subjects (>3ppm breath study. Methonobrevibacter. IBS on and for methane II Ruminococcus not and eligible for Rome C-IBS are subjects with Consecutive IBS sp. subjects Methods: only from Ruminococcus hydrogen stool to al). study, Methanobrevib- by was compared is this production et Ruminococcus humans In methane in flora, (Kassinen, methanogen smithii. facilitate common stool to acter subjects most of donor The hydrogen organisms. study C-IBS methanogenic known recent true in a results a but transit prominent In organisms of transit. methanogenic be model intestinal animal to an of in slowing noted infusion 70% methane This a since testing. breath casual in on than methane more Low, and is constipation Kimberly association between Hwang, association J. the supports Laura Evidence Yang, Janet Pimentel Chou, Mark Y. Test Chang, Jim Breath Christopher Weitsman, Lactulose Stacy on Kim, Methane Gene and IBS Predominant Constipation Methanobrevibacter T1832 IBS. for and important delivery not 1.26). of is o.65, mode colonization CI: by gut % influenced that 95 not suggesting 0.91, was pairs, 1.55). = twin IBS twin 0.65, (OR %) of in (48.8 similar CI: order born development almost % second birth for link sample, was 95 the risk pairs) full and no 1.01, The %) (285 the = was (51.2 Conclusion: pairs in born OR There twin first (adjusted regression discordant the IBS. age logistic and in for IBS gestational Twenty by between discordant IBS. and tested association of weight The were when history birth pairs IBS positive for including a and 297 adjusted symptoms, reported section and twin and caesarean one concordant, illnesses least between 31 were at of pairs, pairs twin checklist and four 321 established a 1967 In was between included which Results: A born registry, questionnaire IBS. Methods: birth twins The pair. national Norwegian Norwegian 1967. the 12700 the within in from to twins identified the 1998 were of In in who order 1979 newborn. sent birth the mode was and including of questionnaire factors vaginal) microflora perinatal postal versus and gut (caesarean IBS the between delivery influence association of the could as evaluated all we utero possible which study for in present infections antibiotics, adjusted perinatal factors illness, of not critical factors. to environmental use were related perinatal and analyses closely with is the of weight birth IBS, birth However, Low group low of confounders. factor. perinatal that this contributing development demonstrated relevant represent delivery for has most of might risk the cohort Mode the pair twin life. increased the G Abstracts AGA lsoytshominis Blastocystis nPtet ihIrtbeBwlSnrm and Syndrome Bowel Irritable With Patients in Smithii B)i rtza omnyfudi h ua digestive human the in found commonly protozoan a is (BH) sPoieti to fSbet With Subjects of Stool in Prominent is S-588 hn6:02±,4v ,501 o A ewe n p<00) hr a loa also 1year). increase was to < IBS. There contribute (occurrence in could 0.05). factor IBS observed This < permeability new patients. IBS (p intestinal occludin, of of (claudin-1, biopsies the 6 case proteins colonic lowest junction in and in tight decreased higher occludin The 3 of is expression ZO-1) of intensity between 0,05). that decrease decrease shows pain VAS < study a important abdominal This for p Conclusion: more only an 0,55±0,16 (0,26±0,08; a with revealed vs for controls patients 0,24±0,14 IBS trend vs in : of C-IBS observed 6 subgroups was was of of than comparison occludin junctions the case The of tight to in (Table). expression the and controls occluding according the of Mann-Whitney of proteins in proteins than by expression of IBS 3 compared with expression the patients were the The of the blot. deviation, in expression - lower mean The Controls western expression significantly ± Results: by the patients. analyzed tests biopsies, average 3 was colonic Kruskal-Wallis as in occludin) was from ZO-1, intensity post-infectious expressed extracted 9 (claudin-1, symptom was protein results, proteins in IBS the IBS junction D-IBS screening. On tight cases. were of VAS. of 7 patients framework 10-cm controls in IBS the on 20 within A-IBS included. quantified and colonoscopy criteria were and III a 59,65years) 7, Rome underwent age: in the proteins mean fulfilling C-IBS junction years) men, cases, tight 47,69 8 patients the age: IBS women, of 23 mean methods: (12 expression men, and the Materials 2 controls. mucosa women, healthy and (21 colonic patients prospective the IBS this increased between of in This patients aim compare in (IBS). The proteins. syndrome to junction bowel tight was of irritable study alterations the to in due be factor could physiopathological permeability key permeab- paracellular a intestinal is increased an ility that suggested Déchelotte, have studies M. Recent Introduction: Pierre Coëffier Marie, Moïse Anne Ducrotté, Leroi R. Syndrome Gourcerol, Philippe Bowel Guillaume Stephane Irritable Antonietti, Liliana, With Michel Belmonte-Zalar Patients Lecleire, ZO-1 Stéphanie, of and Beutheu-Youmba Mucosa Bertiaux-Vandaële, Occludin Colonic Nathalie Claudin-1, the Proteins, in Junction Reduced Tight is the of Expression The T1834 IBS. with patients in BH of of eradication treatment and the the clinical for primary for both the in indicated BH as is nitazoxanide Nitazoxanide recommends BH. the parvum Therapy for Currently, Unfortu- Antimicrobial therapy. option treatment. to for treatment with Guide used indicated problematic been drug Sanford become no traditionally 2009 has is has resistance There metronidazole associ- drug infection. BH, strong BH nately a of and indicate treatment (IBS) studies the syndrome recent for asymptomatic, bowel be irritable may between BH ation with patients some While fe 4dy oreo hrp ihmtoiao 5 gtd hr een statistically no were There tid. mg 250 We metronidasol (29%). with infection therapy diarrhoea GL with of and patients course examined (29%) 79%(7/17) 14-days in cramps after symptoms and (50%), of abdominal (1/1), pain remission was (36%), epigastric total 2% dull documented history in (86%), syndrome patients fullness CD in (43%), dyspeptic epigastric symptoms and were of frequent heartburn infection Most GL lenght GL (3,5/2,4). chronic Average (4/10), was 2,8kg isolated of patients. HP 12% loss with of weight or in with (0/1) CD HP (22/24) 1% months without and 23,3 in GL GL HP therapy. patients. patients, and metronidasol (9/22) (4/10) GL,CD after 27% 12% months in upper in 2 diagnosed during present patients was collected infection positive aspirate GL GL RESULTS: of loss juice symptomatology duodenal weight dull studied of diarrhoea), We (heartburn, (analysis flatulence, symptoms infection with fullness, GL selected females) endoscopy), epigastric of of 87 presence cramps, and males/ presence and epigastric ultrasound (29 studied pain, abdominal patients We negative epigastric 116 findings. tests, study endoscopy laboratory origin. into upper unknown syndrome,normal enrolled of syndrome dyspeptic We We dyspeptic chronic chronic unclear. METHODS: with is patients & symptomatology in AIMS GL parasitic and of prevalence intestinal presence infection infection the asymptomatic human from studied GL vary prevalent diarrhoea.Chronic infection GL most chronic of manifestations to the Clinical world. is the in (GL) protist lamblia Bozikova Giardia Janka Hyrdel, INTRODUCTION: Rudolf Banovcin, Peter Demeter, Syndrome Michal Dyspeptic Chronic and Giardiasis T1835 of role the determine placebo to Double-blind IBS. warranted patients. with symptomatic had are in which pathogen studies potential controlled therapy a considered during be should discomfort it an gastrointestinal was symptoms, of There the of IBS of patients. complaining of yellowing the follow-up. few reporting resolution at of patients resolved the a 82% most (19/22) and with in and 86% tolerated BH achieved well urine, in BH. was of was cure for cure Nitazoxanide eradication (17/18). positive clinical microbiologic the 94% studies A a between stool years. and correlation had 53 patients excellent IBS was the with population BH of females) the for (18/22) 12 of stools symptoms. age and for related negative mean males re-evaluated IBS with The of (10 were examination resolution those patients they as as follow-up 22 and defined defined Overall Upon was BH response were was days. of Clinical stools cure 14 presence therapy. positive Microbiologic the after for with symptoms. for daily Those IBS rechecked workup. twice stools their serial g their their 1 of had nitazoxanide part Kent, patients Inc., as with (Diagnos-Techs, BH treated microscopy of via then presence examined the stool for their had WA) criteria II/III ROME by lsoytshominis Blastocystis and iri lamblia Giardia eioatrpylori Helicobacter neto.Tecmlt ahgncrl fB ean nla,however unclear, remains BH of role pathogenic complete The infection. Conclusion: nVitro In naut n ncide n a eosrtdatvt against activity demonstrated has and children in and adults in neto H) n ola ies C)i xmndpatients. examined in (CD) disease coeliac and (HP), infection tde.Ti btatrprso h s fnitazoxanide of use the on reports abstract This studies. nti td,ntzxnd a fetv o h treatment the for effective was nitazoxanide study, this In Methods: ainswt igoi fIBS of diagnosis a with Patients lsoytshominis Blastocystis Cryptosporidium npatients in Results: