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Tuteja AK, Leung DT, Fang JC, Talley NJ, Stoddard GJ. Randomized double-blind placebo-controlled study to evaluate the effect of long-acting mesalamine on postinfectious irritable bowel syndrome with diarrhea. Neurogastroenterol Motil 2024; 36:e14889. [PMID: 39104061 DOI: 10.1111/nmo.14889] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2024] [Revised: 07/11/2024] [Accepted: 07/25/2024] [Indexed: 08/07/2024]
Abstract
BACKGROUND A subset of patients with irritable bowel syndrome (IBS) develop their symptoms after gastroenteritis, referred to as postinfectious IBS (PI-IBS). PI-IBS is associated with low-grade intestinal inflammation. Previous studies have evaluated mesalamine, an anti-inflammatory drug, in patients with IBS. We evaluated the efficacy of long-acting mesalamine in patients with PI-IBS. METHODS Sixty-one patients who developed diarrhea-predominant IBS (IBS-D) after gastroenteritis were randomized to receive either 2.4 g of long-acting mesalamine or placebo daily for 8-weeks. The symptoms assessed were abdominal pain, bloating, stool frequency, stool consistency, severity of diarrhea and constipation, satisfaction with bowel habits, and IBS affecting or interfering with life. Quality-of-life (QOL) was assessed using the IBS-QOL questionnaire. The prespecified primary outcome variable was the overall bowel symptom score (BSS) after 8-weeks of treatment. Effect sizes were expressed as standardized mean differences (Cohen's d). RESULTS Fifty-four patients completed the 8-week treatment (n = 28 mesalamine, n = 26 placebo), 49 (91%) were male, and age range 23-71 years (mean ± SD 43 ± 13). Mesalamine demonstrated superior efficacy compared to placebo on the primary outcome variable, overall BSS (Cohen's d = 0.57, p = 0.042). Mesalamine was also superior for the secondary outcome of how much IBS affects your life in general (d = 0.72, p = 0.01). For the secondary outcomes of IBS symptoms, 7 of the 7 symptoms had trends of mesalamine superiority. For the secondary outcomes of IBS-QOL subscales, 8 of 9 had trends of mesalamine superiority. CONCLUSION In patients with PI-IBS, long-acting mesalamine demonstrated to be effective in reducing IBS symptoms and improving QOL.
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Affiliation(s)
- Ashok K Tuteja
- George E. Whalen Veterans Affairs Medical Center, Salt Lake City, Utah, USA
- Divisions of Gastroenterology, University of Utah, Salt Lake City, Utah, USA
| | - Daniel T Leung
- Infectious Diseases, University of Utah, Salt Lake City, Utah, USA
| | - John C Fang
- Divisions of Gastroenterology, University of Utah, Salt Lake City, Utah, USA
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Gutiérrez RL, Porter CK, Harro C, Talaat K, Riddle MS, DeNearing B, Brubaker J, Maciel M, Laird RM, Poole S, Chakraborty S, Maier N, Sack DA, Savarino SJ. Efficacy Evaluation of an Intradermally Delivered Enterotoxigenic Escherichia coli CF Antigen I Fimbrial Tip Adhesin Vaccine Coadministered with Heat-Labile Enterotoxin with LT(R192G) against Experimental Challenge with Enterotoxigenic E. coli H10407 in Healthy Adult Volunteers. Microorganisms 2024; 12:288. [PMID: 38399692 PMCID: PMC10892241 DOI: 10.3390/microorganisms12020288] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2023] [Revised: 01/16/2024] [Accepted: 01/26/2024] [Indexed: 02/25/2024] Open
Abstract
BACKGROUND Enterotoxigenic E. coli (ETEC) is a principal cause of diarrhea in travelers, deployed military personnel, and children living in low to middle-income countries. ETEC expresses a variety of virulence factors including colonization factors (CF) that facilitate adherence to the intestinal mucosa. We assessed the protective efficacy of a tip-localized subunit of CF antigen I (CFA/I), CfaE, delivered intradermally with the mutant E. coli heat-labile enterotoxin, LTR192G, in a controlled human infection model (CHIM). METHODS Three cohorts of healthy adult subjects were enrolled and given three doses of 25 μg CfaE + 100 ng LTR192G vaccine intradermally at 3-week intervals. Approximately 28 days after the last vaccination, vaccinated and unvaccinated subjects were admitted as inpatients and challenged with approximately 2 × 107 cfu of CFA/I+ ETEC strain H10407 following an overnight fast. Subjects were assessed for moderate-to-severe diarrhea for 5 days post-challenge. RESULTS A total of 52 volunteers received all three vaccinations; 41 vaccinated and 43 unvaccinated subjects were challenged and assessed for moderate-to-severe diarrhea. Naïve attack rates varied from 45.5% to 64.7% across the cohorts yielding an overall efficacy estimate of 27.8% (95% confidence intervals: -7.5-51.6%). In addition to reducing moderate-severe diarrhea rates, the vaccine significantly reduced loose stool output and overall ETEC disease severity. CONCLUSIONS This is the first study to demonstrate protection against ETEC challenge after intradermal vaccination with an ETEC adhesin. Further examination of the challenge methodology is necessary to address the variability in naïve attack rate observed among the three cohorts in the present study.
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Affiliation(s)
- Ramiro L. Gutiérrez
- Naval Medical Research Command, Silver Spring, MD 20910, USA; (R.L.G.); (M.S.R.); (R.M.L.); (S.P.); (S.J.S.)
| | - Chad K. Porter
- Naval Medical Research Command, Silver Spring, MD 20910, USA; (R.L.G.); (M.S.R.); (R.M.L.); (S.P.); (S.J.S.)
| | - Clayton Harro
- Center for Immunization Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21224, USA (K.T.); (B.D.); (D.A.S.)
| | - Kawsar Talaat
- Center for Immunization Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21224, USA (K.T.); (B.D.); (D.A.S.)
| | - Mark S. Riddle
- Naval Medical Research Command, Silver Spring, MD 20910, USA; (R.L.G.); (M.S.R.); (R.M.L.); (S.P.); (S.J.S.)
| | - Barbara DeNearing
- Center for Immunization Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21224, USA (K.T.); (B.D.); (D.A.S.)
| | - Jessica Brubaker
- Center for Immunization Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21224, USA (K.T.); (B.D.); (D.A.S.)
| | - Milton Maciel
- Naval Medical Research Command, Silver Spring, MD 20910, USA; (R.L.G.); (M.S.R.); (R.M.L.); (S.P.); (S.J.S.)
- Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD 20817, USA
| | - Renee M. Laird
- Naval Medical Research Command, Silver Spring, MD 20910, USA; (R.L.G.); (M.S.R.); (R.M.L.); (S.P.); (S.J.S.)
- Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD 20817, USA
| | - Steven Poole
- Naval Medical Research Command, Silver Spring, MD 20910, USA; (R.L.G.); (M.S.R.); (R.M.L.); (S.P.); (S.J.S.)
- Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD 20817, USA
| | - Subra Chakraborty
- Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA;
| | | | - David A. Sack
- Center for Immunization Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21224, USA (K.T.); (B.D.); (D.A.S.)
| | - Stephen J. Savarino
- Naval Medical Research Command, Silver Spring, MD 20910, USA; (R.L.G.); (M.S.R.); (R.M.L.); (S.P.); (S.J.S.)
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España-Cueto S, Oliveira-Souto I, Salvador F, Goterris L, Treviño B, Sánchez-Montalvá A, Serre-Delcor N, Sulleiro E, Rodríguez V, Aznar ML, Bosch-Nicolau P, Espinosa-Pereiro J, Pou D, Molina I. Post-infectious irritable bowel syndrome following a diagnosis of traveller's diarrhoea: a comprehensive characterization of clinical and laboratory parameters. J Travel Med 2023; 30:taad030. [PMID: 36881659 DOI: 10.1093/jtm/taad030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2022] [Revised: 02/20/2023] [Accepted: 02/21/2023] [Indexed: 03/09/2023]
Abstract
BACKGROUND Prolonged or recurrent gastrointestinal symptoms may persist after acute traveller's diarrhoea (TD), even after adequate treatment of the primary cause. This study aims to describe the epidemiological, clinical and microbiological characteristics of patients with post-infectious irritable bowel syndrome (PI-IBS) after returning from tropical or subtropical areas. METHODS We conducted a retrospective study of patients presenting between 2009 and 2018 at the International Health referral centre in Barcelona with persistent gastrointestinal symptoms following a diagnosis of TD. PI-IBS was defined as the presence of persistent or recurrent gastrointestinal manifestations for at least 6 months after the diagnosis of TD, a negative stool culture for bacterial pathogens and a negative ova and parasite exam after targeted treatment. Epidemiological, clinical and microbiological variables were collected. RESULTS We identified 669 travellers with a diagnosis of TD. Sixty-eight (10.2%) of these travellers, mean age 33 years and 36 (52.9%) women, developed PI-IBS. The most frequently visited geographical areas were Latin America (29.4%) and the Middle East (17.6%), with a median trip duration of 30 days (IQR 14-96). A microbiological diagnosis of TD was made in 32 of these 68 (47%) patients, 24 (75%) of whom had a parasitic infection, Giardia duodenalis being the most commonly detected parasite (n = 20, 83.3%). The symptoms persisted for a mean of 15 months after diagnosis and treatment of TD. The multivariate analysis revealed that parasitic infections were independent risk factors for PI-IBS (OR 3.0, 95%CI 1.2-7.8). Pre-travel counselling reduced the risk of PI-IBS (OR 0.4, 95%CI 0.2-0.9). CONCLUSIONS In our cohort, almost 10% of patients with travellers' diarrhoea developed persistent symptoms compatible with PI-IBS. Parasitic infections, mainly giardiasis, seem to be associated with PI-IBS.
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Affiliation(s)
- Sergio España-Cueto
- International Health Unit Vall d'Hebron-Drassanes, Infectious Diseases Department, Vall d'Hebron University Hospital, PROSICS Barcelona, Universitat Autònoma de Barcelona, Barcelona, Spain
- Infectious Diseases Department, Germans Trias i Pujol University Hospital, Badalona, Spain
- The Fight Infections Foundation, Badalona, Spain
| | - Inés Oliveira-Souto
- International Health Unit Vall d'Hebron-Drassanes, Infectious Diseases Department, Vall d'Hebron University Hospital, PROSICS Barcelona, Universitat Autònoma de Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain
| | - Fernando Salvador
- International Health Unit Vall d'Hebron-Drassanes, Infectious Diseases Department, Vall d'Hebron University Hospital, PROSICS Barcelona, Universitat Autònoma de Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain
| | - Lidia Goterris
- Department of Microbiology, Vall d'Hebron University Hospital and PROSICS, Barcelona, Spain
| | - Begoña Treviño
- International Health Unit Vall d'Hebron-Drassanes, Infectious Diseases Department, Vall d'Hebron University Hospital, PROSICS Barcelona, Universitat Autònoma de Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain
| | - Adrián Sánchez-Montalvá
- International Health Unit Vall d'Hebron-Drassanes, Infectious Diseases Department, Vall d'Hebron University Hospital, PROSICS Barcelona, Universitat Autònoma de Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain
| | - Núria Serre-Delcor
- International Health Unit Vall d'Hebron-Drassanes, Infectious Diseases Department, Vall d'Hebron University Hospital, PROSICS Barcelona, Universitat Autònoma de Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain
| | - Elena Sulleiro
- Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain
- Department of Microbiology, Vall d'Hebron University Hospital and PROSICS, Barcelona, Spain
| | - Virginia Rodríguez
- Department of Microbiology, Vall d'Hebron University Hospital and PROSICS, Barcelona, Spain
| | - Maria Luisa Aznar
- International Health Unit Vall d'Hebron-Drassanes, Infectious Diseases Department, Vall d'Hebron University Hospital, PROSICS Barcelona, Universitat Autònoma de Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain
| | - Pau Bosch-Nicolau
- International Health Unit Vall d'Hebron-Drassanes, Infectious Diseases Department, Vall d'Hebron University Hospital, PROSICS Barcelona, Universitat Autònoma de Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain
| | - Juan Espinosa-Pereiro
- International Health Unit Vall d'Hebron-Drassanes, Infectious Diseases Department, Vall d'Hebron University Hospital, PROSICS Barcelona, Universitat Autònoma de Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain
| | - Diana Pou
- International Health Unit Vall d'Hebron-Drassanes, Infectious Diseases Department, Vall d'Hebron University Hospital, PROSICS Barcelona, Universitat Autònoma de Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain
| | - Israel Molina
- International Health Unit Vall d'Hebron-Drassanes, Infectious Diseases Department, Vall d'Hebron University Hospital, PROSICS Barcelona, Universitat Autònoma de Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain
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Herrick T. Health Care of the International Traveler. Fam Med 2022. [DOI: 10.1007/978-3-030-54441-6_9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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Abstract
Following acute gastroenteritis (AGE) due to bacteria, viruses, or protozoa, a subset of patients develop new onset Rome criteria positive irritable bowel syndrome (IBS), called postinfection IBS (PI-IBS). The pooled prevalence of PI-IBS following AGE was 11.5%. PI-IBS is the best natural model that suggests that a subset of patients with IBS may have an organic basis. Several factors are associated with a greater risk of development of PI-IBS following AGE including female sex, younger age, smoking, severity of AGE, abdominal pain, bleeding per rectum, treatment with antibiotics, anxiety, depression, somatization, neuroticism, recent adverse life events, hypochondriasis, extroversion, negative illness beliefs, history of stress, sleep disturbance, and family history of functional gastrointestinal disorders (FGIDs), currently called disorder of gut-brain interaction. Most patients with PI-IBS present with either diarrhea-predominant IBS or the mixed subtype of IBS, and overlap with other FGIDs, such as functional dyspepsia is common. The drugs used to treat non-constipation IBS may also be useful in PI-IBS treatment. Since randomized controlled trials on the efficacy of drugs to treat PI-IBS are rare, more studies are needed on this issue.
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Affiliation(s)
- Uday C Ghoshal
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
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Hujoel IA, Wu TT, Sweetser S. Diarrhea in a Retired Couple From Mexico. Gastroenterology 2021; 160:1039-1040. [PMID: 32565013 DOI: 10.1053/j.gastro.2020.05.094] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2020] [Accepted: 05/11/2020] [Indexed: 12/02/2022]
Affiliation(s)
- Isabel A Hujoel
- Department of Internal Medicine and Division of Gastroenterology and Hepatology.
| | - Tsung-Teh Wu
- Department of Anatomic Pathology, Mayo Clinic College of Medicine, Rochester, Minnesota
| | - Seth Sweetser
- Department of Internal Medicine and Division of Gastroenterology and Hepatology
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Balmus IM, Ciobica A, Cojocariu R, Luca AC, Gorgan L. Irritable Bowel Syndrome and Neurological Deficiencies: Is There A Relationship? The Possible Relevance of the Oxidative Stress Status. ACTA ACUST UNITED AC 2020; 56:medicina56040175. [PMID: 32295083 PMCID: PMC7230401 DOI: 10.3390/medicina56040175] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2020] [Revised: 04/06/2020] [Accepted: 04/08/2020] [Indexed: 12/12/2022]
Abstract
Background: Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorders, exhibiting complex and controversial pathological features. Both oxidative stress and inflammation-related reactive oxygen species production may be involved in IBS pathological development. Thus, we focused on several aspects regarding the causes of oxidative stress occurrence in IBS. Additionally, in the molecular context of oxidative changes, we tried to discuss these possible neurological implications in IBS. Methods: The literature search included the main available databases (e.g., ScienceDirect, Pubmed/Medline, Embase, and Google Scholar). Articles in the English language were taken into consideration. Our screening was conducted based on several words such as “irritable bowel syndrome”, “gut brain axis”, “oxidative stress”, “neuroendocrine”, and combinations. Results: While no consistent evidence suggests clear pathway mechanisms, it seems that the inflammatory response may also be relevant in IBS. The mild implication of oxidative stress in IBS has been described through clinical studies and some animal models, revealing changes in the main markers such as antioxidant status and peroxidation markers. Moreover, it seems that the neurological structures involved in the brain-gut axis may be affected in IBS rather than the local gut tissue and functionality. Due to a gut-brain axis bidirectional communication error, a correlation between neurological impairment, emotional over-responsiveness, mild inflammatory patterns, and oxidative stress can be suggested. Conclusions: Therefore, there is a possible correlation between neurological impairment, emotional over-responsiveness, mild inflammatory patterns, and oxidative stress that are not followed by tissue destruction in IBS patients. Moreover, it is not yet clear whether oxidative stress, inflammation, or neurological impairments are key determinants or in which way these three interact in IBS pathology. However, the conditions in which oxidative imbalances occur may be an interesting research lead in order to find possible explanations for IBS development.
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Affiliation(s)
- Ioana-Miruna Balmus
- Department of Interdisciplinary Research in Science, “Alexandru Ioan Cuza” University of Iasi, Carol I Avenue, No. 11, 700506 Iași, Romania;
- Department of Research, Faculty of Biology, “Alexandru Ioan Cuza” University of Iasi, Carol I Avenue, 20A, 700506 Iași, Romania
| | - Alin Ciobica
- Department of Research, Faculty of Biology, “Alexandru Ioan Cuza” University of Iasi, Carol I Avenue, 20A, 700506 Iași, Romania
- Correspondence: (A.C.); (A.-C.L.)
| | - Roxana Cojocariu
- Department of Biology, Faculty of Biology, “Alexandru Ioan Cuza” University of Iasi, Carol I Avenue, 20A, 700506 Iași, Romania; (R.C.); (L.G.)
| | - Alina-Costina Luca
- Faculty of Medicine, “Gr. T. Popa” University of Medicine and Pharmacy, 16th University Street, 700115 Iași, Romania
- Correspondence: (A.C.); (A.-C.L.)
| | - Lucian Gorgan
- Department of Biology, Faculty of Biology, “Alexandru Ioan Cuza” University of Iasi, Carol I Avenue, 20A, 700506 Iași, Romania; (R.C.); (L.G.)
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Pogreba-Brown K, Austhof E, Armstrong A, Schaefer K, Zapata LV, McClelland DJ, Batz MB, Kuecken M, Riddle M, Porter CK, Bazaco MC. Chronic Gastrointestinal and Joint-Related Sequelae Associated with Common Foodborne Illnesses: A Scoping Review. Foodborne Pathog Dis 2020; 17:67-86. [PMID: 31589475 PMCID: PMC9246095 DOI: 10.1089/fpd.2019.2692] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
To strengthen the burden estimates for chronic sequelae of foodborne illness, we conducted a scoping review of the current literature for common foodborne pathogens and their associated sequelae. We aim to describe the current literature and gaps in knowledge of chronic sequelae associated with common foodborne illnesses. A comprehensive search was conducted in PubMed, EMBASE, and Web of Science for peer-reviewed articles published January 1, 2000 to April 1, 2018. Articles available in English, of any epidemiological study design, for 10 common foodborne pathogens (Campylobacter, Salmonella, Escherichia coli, Listeria, Shigella, Cryptosporidium, Cyclospora, Giardia, Yersinia, and norovirus) and their associated gastrointestinal (GI)- and joint-related sequelae were included. Of the 6348 titles screened for inclusion, 380 articles underwent full-text review; of those 380, 129 were included for data extraction. Of the bacterial pathogens included in the search terms, the most commonly reported were Salmonella (n = 104) and Campylobacter (n = 99); E. coli (n = 55), Shigella (n = 49), Yersinia (n = 49), and Listeria (n = 15) all had fewer results. Norovirus was the only virus included in our search, with 28 article that reported mostly GI-related sequelae and reactive arthritis (ReA) reported once. For parasitic diseases, Giardia (n = 26) and Cryptosporidium (n = 18) had the most articles, and no results were found for Cyclospora. The most commonly reported GI outcomes were irritable bowel syndrome (IBS; n = 119) and inflammatory bowel disease (n = 29), and ReA (n = 122) or "joint pain" (n = 19) for joint-related sequelae. Salmonella and Campylobacter were most often associated with a variety of outcomes, with ReA (n = 34 and n = 27) and IBS (n = 17 and n = 20) reported most often. This scoping review shows there are still a relatively small number of studies being conducted to understand specific pathogen/outcome relationships. It also shows where important gaps in the impact of chronic sequelae from common foodborne illnesses still exist and where more focused research would best be implemented.
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Affiliation(s)
- Kristen Pogreba-Brown
- Epidemiology & Biostatistics Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, Arizona
| | - Erika Austhof
- Epidemiology & Biostatistics Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, Arizona
| | - Alexandra Armstrong
- Epidemiology & Biostatistics Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, Arizona
| | - Kenzie Schaefer
- Epidemiology & Biostatistics Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, Arizona
| | - Lorenzo Villa Zapata
- Epidemiology & Biostatistics Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, Arizona
| | | | | | - Maria Kuecken
- U.S. Food and Drug Administration, College Park, Maryland
| | - Mark Riddle
- Naval Medical Research Center, Silver Spring, Maryland
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Health Care of the International Traveler. Fam Med 2020. [DOI: 10.1007/978-1-4939-0779-3_9-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Suciu A, Popa SL, Dumitrascu DL. Upper Gastrointestinal Sensitization And Symptom Generation. J Med Life 2019; 12:316-321. [PMID: 32025247 PMCID: PMC6993284 DOI: 10.25122/jml-2019-0111] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2019] [Accepted: 11/20/2019] [Indexed: 12/29/2022] Open
Abstract
Functional gastrointestinal disorders (FGIDs) are a highly prevalent group of heterogeneous disorders, and their diagnostic criteria are symptom-based, with the absence of anatomical and biochemical abnormalities of the gastrointestinal tract. Chronic visceral symptoms are common both in patients with an identifiable organic disease but also in FGID patients. Patients suffering from upper gastrointestinal functional disorders typically present with various symptoms such as early satiety, postprandial fullness, bloating, nausea, vomiting, and epigastric pain. Considering their increasing prevalence, difficulties in diagnosis, and low quality of life, FGIDs have become an emerging problem in gastroenterology. We aimed to provide an updated summary of pathways involved in visceral sensitization. We examined the recent literature searching for evidence of the most important studies about the mechanisms underlying gastrointestinal symptom generation and sensitization.
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Affiliation(s)
| | - Stefan-Lucian Popa
- Second Medical Department “Iuliu Hatieganu” University of Medicine and Pharmacy Cluj-Napoca, Romania
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Svendsen AT, Bytzer P, Engsbro AL. Systematic review with meta-analyses: does the pathogen matter in post-infectious irritable bowel syndrome? Scand J Gastroenterol 2019; 54:546-562. [PMID: 31112663 DOI: 10.1080/00365521.2019.1607897] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Objective: Acute gastroenteritis (AGE) is a risk factor for post-infectious irritable bowel syndrome (PI-IBS). This systematic review evaluates the prevalence and risk-factors of PI-IBS after AGE by specific pathogens. Materials and methods: Medline (1966-2019) and Embase (1974-2019) were searched for studies evaluating PI-IBS minimum 3 months after AGE with Campylobacter spp., Salmonella spp., Shigella spp., Escherischia coli, Clostridium difficile, norovirus, rotavirus, Cryptosporidium spp. or Giardia intestinalis using validated criteria for IBS. Pooled prevalence (PP), odds ratios (OR) and risk factors were determined for single pathogens, groups of bacteria, viruses and parasites, and overall for AGE caused by any pathogen. Random-effect models were used for meta-analyses. Results: A total of 34 articles were included. PP of PI-IBS after Campylobacter spp. was 12% (confidence interval 95% [CI]: 10-15%), Salmonellosis 12% (CI: 9-15%), Shigellosis 11% (CI: 8-15%), C. difficile 14% (CI: 4-29%) and E. coli spp. 12% (CI: 5-20%). OR of PI-IBS after salmonellosis was 5.5 (CI: 2.3-12.8) and after shigellosis 13.8 (CI: 4.2-45.4). Bacterial AGE overall showed OR 5.8 (CI: 4.0-8.3) and AGE caused by any pathogen OR 4.9 (CI: 3.9-6.1). Few studies exist on viral and parasitic gastroenteritis. Conclusions: Current literature show similar risks for bacterial pathogens. Studies are limited for viral and parasitic pathogens. The evaluated risk-factors for PI-IBS varied among the included studies and the existing evidence is insufficient to identify pathogen-specific risk factors.
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Affiliation(s)
- Anna Tølbøll Svendsen
- a Department of Gastroenterology , Zealand University Hospital , Køge , Denmark.,b Department of Clinical Medicine , Copenhagen University , Copenhagen N , Denmark
| | - Peter Bytzer
- a Department of Gastroenterology , Zealand University Hospital , Køge , Denmark.,b Department of Clinical Medicine , Copenhagen University , Copenhagen N , Denmark
| | - Anne Line Engsbro
- c Department of Clinical Microbiology , Copenhagen University Hospital Hvidovre , Hvidovre , Denmark
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Florens MV, Van Wanrooy S, Dooley J, Aguilera-Lizarraga J, Vanbrabant W, Wouters MM, Van Oudenhove L, Peetermans WE, Liston A, Boeckxstaens GE. Prospective study evaluating immune-mediated mechanisms and predisposing factors underlying persistent postinfectious abdominal complaints. Neurogastroenterol Motil 2019; 31:e13542. [PMID: 30657233 DOI: 10.1111/nmo.13542] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2018] [Revised: 11/20/2018] [Accepted: 12/10/2018] [Indexed: 12/13/2022]
Abstract
BACKGROUND The role of persistent immune activation in postinfectious irritable bowel syndrome (PI-IBS) remains controversial. Here, we prospectively studied healthy subjects traveling to destinations with a high-risk to develop infectious gastroenteritis (IGE) in order to identify immune-mediated mechanisms and risk factors of PI-IBS. METHODS One hundred and one travelers were asked to complete questionnaires on psychological profile and gastrointestinal (GI) symptoms before travel, 2 weeks, 6 months and 1 year after travel. At each visit, blood was collected for PBMC isolation and rectal biopsies were taken. PI-IBS was diagnosed using the Rome III criteria and subjects with persistent postinfectious abdominal complaints (PI-AC) were identified using 3 GSRS symptoms (ie, loose stools, urgency and abdominal pain). RESULTS Forty-seven of the 101 subjects reported IGE during travel. After 1 year, two subjects were diagnosed with PI-IBS and eight subjects were presented with PI-AC versus two subjects with IBS and two with abdominal complaints in the non-infected group. PBMC analysis showed no differences in T and B cell populations in subjects with PI-AC vs healthy. Additionally, no differences in gene expression were observed in the early postinfectious phase or after 1 year. Regression analysis identified looser stools, higher anxiety and somatization before infection and several postinfectious GI symptoms as risk factors for PI-AC. CONCLUSIONS The incidence of PI-IBS is low following travelers' diarrhea and there is need for larger studies investigating the role of immune activation in PI-IBS. Psychological factors before infection and the severity of symptoms shortly after infection are risk factors for the persistence of PI-AC.
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Affiliation(s)
- Morgane V Florens
- Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, Leuven, Belgium
| | - Sander Van Wanrooy
- Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, Leuven, Belgium
| | - James Dooley
- Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium.,Autoimmune Genetics Laboratory, VIB, Leuven, Belgium
| | | | - Winde Vanbrabant
- Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, Leuven, Belgium
| | - Mira M Wouters
- Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, Leuven, Belgium
| | - Lukas Van Oudenhove
- Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, Leuven, Belgium
| | - Willy E Peetermans
- Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium.,Laboratory for Clinical Infectious and Inflammatory Disorders, KU Leuven, Leuven, Belgium
| | - Adrian Liston
- Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium.,Autoimmune Genetics Laboratory, VIB, Leuven, Belgium
| | - Guy E Boeckxstaens
- Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, Leuven, Belgium
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13
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Ghoshal UC, Rahman MM. Post-infection irritable bowel syndrome in the tropical and subtropical regions: Vibrio cholerae is a new cause of this well-known condition. Indian J Gastroenterol 2019; 38:87-94. [PMID: 31073702 DOI: 10.1007/s12664-019-00959-2] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Affiliation(s)
- Uday C Ghoshal
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226 014, India.
| | - M Masudur Rahman
- Department of Gastroenterology, Sheikh Russel Gastroliver Institute and Hospital, Dhaka, Bangladesh
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14
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Sadeghi A, Biglari M, Nasseri Moghaddam S. Post-infectious Irritable Bowel Syndrome: A Narrative Review. Middle East J Dig Dis 2019; 11:69-75. [PMID: 31380002 PMCID: PMC6663289 DOI: 10.15171/mejdd.2019.130] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2019] [Accepted: 05/22/2019] [Indexed: 12/12/2022] Open
Abstract
The Irritable bowel syndrome (IBS) is a functional disorder of alimentary system, which may be caused by infectious gastroenteritis determined as post infectious irritable bowel syndrome (PI-IBS). The prevalence of PI-IBS is reported to be 4-36% in patients with infectious gastroenteritis. The exact mechanism leading to PI-IBS is not fully understood and some factors pertaining to infectious agent and host response may have a role. Rome IV diagnostic criteria provided new definition for PI-IBS. Though it is now considered a well-defined functional disorder of gastrointestinal system, no specific treatment is yet available for PI-IBS. This article reviews the latest issues on these heading about PI-IBS.
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Affiliation(s)
- Anahita Sadeghi
- Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Biglari
- Department of Internal Medicine, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Siavosh Nasseri Moghaddam
- Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
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15
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Vojdani A, Vojdani E. Reaction of antibodies to Campylobacter jejuni and cytolethal distending toxin B with tissues and food antigens. World J Gastroenterol 2019; 25:1050-1066. [PMID: 30862994 PMCID: PMC6406185 DOI: 10.3748/wjg.v25.i9.1050] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2018] [Revised: 01/16/2019] [Accepted: 01/26/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The bacteria Campylobacter jejuni (C. jejuni) is commonly associated with Guillane-Barré syndrome (GBS) and irritable bowel syndrome (IBS), but studies have also linked it with Miller Fisher syndrome, reactive arthritis and other disorders, some of which are autoimmune. It is possible that C. jejuni and its toxins may be cross-reactive with some human tissues and food antigens, potentially leading to autoimmune responses.
AIM To measure the immune reactivity of C. jejuni and C. jejuni cytolethal distending toxin (Cdt) antibodies with tissue and food antigens to examine their role in autoimmunities.
METHODS Using enzyme-linked immunosorbent assay (ELISA) methodology, specific antibodies made against C. jejuni and C. jejuni Cdt were applied to a variety of microwell plates coated with 45 tissues and 180 food antigens. The resulting immunoreactivities were compared to reactions with control wells coated with human serum albumin (HSA) which were used as negative controls and with wells coated with C. jejuni lysate or C. jejuni Cdt which served as positive controls.
RESULTS At 3 SD above the mean of control wells coated with HSA or 0.41 OD, the mouse monoclonal antibody made against C. jejuni showed moderate to high reactions with zonulin, somatotropin, acetylcholine receptor, β-amyloid and presenilin. This immune reaction was low with an additional 25 tissue antigens including asialoganglioside, and the same antibody did not react at all with another 15 tissue antigens. Examining the reaction between C. jejuni antibody and 180 food antigens, we found insignificant reactions with 163 foods but low to high immune reactions with 17 food antigens. Similarly, we examined the reaction of C. jejuni Cdt with the same tissues and food antigens. The strongest reactions were observed with zonulin, intrinsic factor and somatotropin. The reaction was moderate with 9 different tissue antigens including thyroid peroxidase, and reaction was low with another 10 different antigens, including neuronal antigens. The reaction of C. jejuni Cdt antibody with an additional 23 tissue antigens was insignificant. Regarding the reaction of C. jejuni Cdt antibody with different food antigens, 160 out of 180 foods showed insignificant reactions, while 20 foods showed reactions ranging from low to high.
CONCLUSION Our findings indicate that C. jejuni and its Cdt may play a role in inflammation and autoimmunities beyond the gut.
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Affiliation(s)
- Aristo Vojdani
- Immunosciences Lab., Inc., Los Angeles, CA 90035, United States
- Cyrex Labs, LLC., Phoenix, AZ 85034, United States
- Department of Preventive Medicine, Loma Linda University School of Medicine, Loma Linda, CA 92354, United States
| | - Elroy Vojdani
- Regenera Medical, Los Angeles, CA 90025, United States
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16
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Abstract
PURPOSE OF REVIEW Review recent developments pertaining to the epidemiology, molecular pathogenesis, and sequelae of enterotoxigenic Escherichia coli (ETEC) infections in addition to discussion of challenges for vaccinology. RECENT FINDINGS ETEC are a major cause of diarrheal illness in resource poor areas of the world where they contribute to unacceptable morbidity and continued mortality particularly among young children; yet, precise epidemiologic estimates of their contribution to death and chronic disease have been difficult to obtain. Although most pathogenesis studies, and consequently vaccine development have focused intensively on canonical antigens, more recently identified molecules unique to the ETEC pathovar may inform our understanding of ETEC virulence, and the approach to broadly protective vaccines. ETEC undeniably continue to have a substantial impact on global health; however, further studies are needed to clarify the true impact of these infections, particularly in regions where access to care may be limited. Likewise, our present understanding of the relationship of ETEC infection to non-diarrheal sequelae is presently limited, and additional effort will be required to achieve a mechanistic understanding of these diseases and to fulfill Koch's postulates on a molecular level. Precise elucidation of the role played by novel virulence factors, the global burden of acute illness, and the contribution of these pathogens and/or their toxins to non-diarrheal morbidity remain important imperatives.
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Affiliation(s)
- James M Fleckenstein
- Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, 660 South Euclid Avenue, Saint Louis, MO, 63110, USA.
- Medicine Service, Veterans Affairs Medical Center, Saint Louis, MO, USA.
| | - F Matthew Kuhlmann
- Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, 660 South Euclid Avenue, Saint Louis, MO, 63110, USA
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17
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Lindsay L, DuPont HL, Moe CL, Alberer M, Hatz C, Kirby AE, Wu HM, Verstraeten T, Steffen R. Estimating the incidence of norovirus acute gastroenteritis among US and European international travelers to areas of moderate to high risk of traveler's diarrhea: a prospective cohort study protocol. BMC Infect Dis 2018; 18:605. [PMID: 30509202 PMCID: PMC6276235 DOI: 10.1186/s12879-018-3461-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2017] [Accepted: 10/31/2018] [Indexed: 12/31/2022] Open
Abstract
Background Acute gastroenteritis (AGE) is the leading cause of illness among returning travelers seeking medical care. Multiple types of enteric pathogens can cause travel-acquired AGE and, while bacterial pathogens have a predominant role, the importance of viruses, such as norovirus, is increasingly recognized. There is a lack of information on travel-acquired norovirus incidence among symptomatic and asymptomatic individuals irrespective of healthcare-seeking behavior. Our aim is to estimate the incidence of travel-acquired AGE due to norovirus and to characterize the burden of disease among international travelers from the United States and Europe. Methods We describe a prospective cohort study implemented in five US and European sites to estimate the role of AGE due to norovirus among adult international travelers. We enrolled individuals aged 18 years and older who are traveling to regions of moderate-high risk of AGE, or via cruise ship with an international port stop, with a trip duration of 3–15 days. The study will generate a wide range of health and travel-related data for pre-, during, and up to 6-months post-travel. We will identify laboratory-confirmed travel-acquired norovirus infections among both symptomatic and asymptomatic individuals from self-collected whole stool samples tested via quantitative RT-PCR. Coinfections will be identified in a subset of travelers with AGE using a multiplex molecular-based assay. Discussion This study is unique in design and breadth of data collected. The prospective collection of health and behavioral data, as well as biologic samples from travelers irrespective of symptoms, will provide useful data to better understand the importance of norovirus AGE among international travelers. This study will provide data to estimate the incidence of norovirus infections and AGE and the risk of post-infectious sequelae in the 6-month post-travel period serving as a baseline for future norovirus AGE vaccination studies. This study will contribute valuable information to better understand the role of norovirus in travel-acquired AGE risk and the impact of these infections on a broad set of outcomes.
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Affiliation(s)
- Lisa Lindsay
- P95 Pharmacovigilance and Epidemiology Services, Koning Leopold III Laan 1, 3001, Leuven, Belgium.
| | - Herbert L DuPont
- University of Texas McGovern Medical School and School of Public Health, 1200 Pressler Street, Houston, TX, 77030, USA
| | - Christine L Moe
- Emory University, Rollins School of Public Health, 1518 Clifton Road NE, Atlanta, GA, 30322, USA
| | - Martin Alberer
- Division of Infectious Diseases and Tropical Medicine, University Hospital, Ludwig-Maximilians-University (LMU) Munich, Leopoldstrasse 5, 80802, Munich, Germany
| | - Christoph Hatz
- Swiss Tropical and Public Health Institute, Socinstrasse 57, 4056, Basel, Switzerland.,University of Basel, Petersplatz 1, 4001, Basel, Switzerland.,University of Zurich; Epidemiology, Biostatistics and Prevention Institute, WHO Collaborating Centre for Travellers' Health, Hirschengraben 84, 8001, Zurich, Switzerland
| | - Amy E Kirby
- Emory University, Rollins School of Public Health, 1518 Clifton Road NE, Atlanta, GA, 30322, USA
| | - Henry M Wu
- Emory University, Division of Infectious Diseases, Department of Medicine, 550 Peachtree Street NE MOT 7, Atlanta, GA, 30308, USA
| | - Thomas Verstraeten
- P95 Pharmacovigilance and Epidemiology Services, Koning Leopold III Laan 1, 3001, Leuven, Belgium
| | - Robert Steffen
- University of Texas McGovern Medical School and School of Public Health, 1200 Pressler Street, Houston, TX, 77030, USA.,University of Zurich; Epidemiology, Biostatistics and Prevention Institute, WHO Collaborating Centre for Travellers' Health, Hirschengraben 84, 8001, Zurich, Switzerland
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18
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Lääveri T, Vilkman K, Pakkanen S, Kirveskari J, Kantele A. Despite antibiotic treatment of travellers' diarrhoea, pathogens are found in stools from half of travellers at return. Travel Med Infect Dis 2018; 23:49-55. [PMID: 29702254 DOI: 10.1016/j.tmaid.2018.04.003] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2017] [Revised: 03/24/2018] [Accepted: 04/09/2018] [Indexed: 01/01/2023]
Abstract
BACKGROUND Among visitors to the (sub)tropics, 20-50% contract travellers' diarrhoea (TD) and 5-30% take antibiotics. While shortening the duration of illness, antimicrobials predispose to acquisition of multi-drug resistant bacteria. Therefore, liberal use is no longer advocated. Although antibiotics kill pathogens, no data support the view that they could prevent post-infectious sequelae. We investigated how antibiotic use for TD abroad impacts the pathogen findings at return. MATERIALS AND METHODS We revisited 456 travellers' clinical data and stool pathogens examined by qPCR for Salmonella, Yersinia, Campylobacter, Shigella, Vibrio cholerae and enteroaggregative (EAEC), enteropathogenic (EPEC), enterotoxigenic (ETEC), enterohaemorrhagic (EHEC) and enteroinvasive (EIEC) Escherichia coli. RESULTS Among travellers with TD, antibiotic users had pathogen-positive samples less frequently than non-users (50% versus 83%). The difference was significant for EPEC (23% versus 47%) and EAEC (27% versus 54%), but not ETEC (17% versus 26%) or the other pathogens. Shigella/EIEC was found more often among antibiotic users than non-users (4% versus 1%). CONCLUSION Despite antibiotic treatment of TD, half of the users still had stool pathogens at return, reflecting either antibiotic resistance of pathogens or recolonisation/reinfection while abroad. Treatment of TD with antibiotics during travel should not be interpreted to indicate eradication of pathogens.
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Affiliation(s)
- Tinja Lääveri
- Inflammation Center, Division of Infectious Diseases, University of Helsinki and Helsinki University Hospital, Helsinki, Finland, POB 348, FIN-00029 HUS, Finland.
| | - Katri Vilkman
- Inflammation Center, Division of Infectious Diseases, University of Helsinki and Helsinki University Hospital, Helsinki, Finland, POB 348, FIN-00029 HUS, Finland.
| | - Sari Pakkanen
- Department of Bacteriology and Immunology, University of Helsinki, Helsinki, Finland, POB 21, FIN-00014 Helsinki, Finland.
| | - Juha Kirveskari
- Helsinki University Hospital Laboratory (HUSLAB), Department of Bacteriology, Helsinki, Finland, POB 720, FIN-00029 HUS, Finland; Mobidiag Ltd, Espoo, Finland, Keilaranta 16 A, FIN-02150 Espoo Finland.
| | - Anu Kantele
- Inflammation Center, Division of Infectious Diseases, University of Helsinki and Helsinki University Hospital, Helsinki, Finland, POB 348, FIN-00029 HUS, Finland; Clinicum, University of Helsinki, Helsinki, Finland, POB 63, FI-00014 Helsinki, Finland; Aava Travel Clinic, Medical Centre Aava, Helsinki, Finland, Annankatu 32, FIN-00100 Helsinki, Finland; Unit of Infectious Diseases, Department of Medicine/Solna, Karolinska Institutet, Stockholm, Sweden, SE-17176 Stockholm, Sweden.
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19
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Lääveri T, Pakkanen SH, Kirveskari J, Kantele A. Travellers' diarrhoea: Impact of TD definition and control group design on study results. Travel Med Infect Dis 2018; 24:37-43. [PMID: 29409749 DOI: 10.1016/j.tmaid.2018.01.006] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2017] [Revised: 01/24/2018] [Accepted: 01/25/2018] [Indexed: 01/17/2023]
Abstract
BACKGROUND Travellers' diarrhoea (TD) is a common health problem among visitors to the (sub)tropics. Much research deals with aetiology, prevention, and post-infection sequalae, yet the data may not allow comparisons due to incompatible definitions of TD and No TD control groups. METHOD The impact of defining TD and No TD control groups was explored by revisiting our recent data. We set up two TD groups: classical TD i.e. ≥3 loose or liquid stools/day and WHO TD (diarrhoea as defined by the WHO) i.e. any diarrhoea, and four No TD groups by TD definition and timing (no classical/WHO TD during travel, no ongoing classical/WHO TD). RESULTS TD was recorded for 37% versus 65% of subjects when using classical versus WHO definitions, respectively; the proportions of the various pathogens proved similar. The strictest criterion for the No TD control group (no WHO TD during travel) yielded pathogens among 61% and the least strict (no ongoing classical TD) among 73% of the travellers; the differences were greatest for enteroaggregative Escherichia coli and Campylobacter. CONCLUSIONS Definition of TD and control group design substantially impact on TD study results. The WHO definition yields more cases, but the pathogen selection is similar by both definitions. Design of the No TD control group was found critical: only those remaining asymptomatic throughout the journey should be included.
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Affiliation(s)
- Tinja Lääveri
- Inflammation Center, Division of Infectious Diseases, University of Helsinki and Helsinki University Hospital, POB 348, FIN-00029 HUS, Helsinki, Finland
| | - Sari H Pakkanen
- Department of Bacteriology and Immunology, University of Helsinki, P.O. Box 21, FIN-00014 Helsinki, Finland
| | - Juha Kirveskari
- Helsinki University Hospital Laboratory (HUSLAB), Department of Bacteriology, POB 720, FIN-00029 HUS, Helsinki, Finland; Mobidiag Ltd, Keilaranta 16 A, FIN-02150 Espoo, Finland
| | - Anu Kantele
- Inflammation Center, Division of Infectious Diseases, University of Helsinki and Helsinki University Hospital, POB 348, FIN-00029 HUS, Helsinki, Finland; Clinicum, University of Helsinki, PO Box 63, FIN-00014, Helsinki, Finland; Aava Travel Clinic, Medical Centre Aava, Annankatu 32, FIN-00100 Helsinki, Finland; Unit of Infectious Diseases, Department of Medicine/Solna, Karolinska Institutet, SE-17176 Stockholm, Sweden.
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20
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Abstract
PURPOSE OF REVIEW Post-infectious irritable bowel syndrome (PI-IBS) is characterized by persistent abdominal pain and diarrhea, typically following an episode of infectious gastroenteritis. The mechanisms that underlie IBS-D remain elusive, but PI-IBS provides a mechanistic model of this disorder. This review provides an up-to-date appraisal of the pathophysiology, clinical features, and management approaches for PI-IBS. RECENT FINDINGS Disordered immune reactions and release of cytokines with resultant gut inflammation and dysfunction appear to be key features of PI-IBS. Disordered brain-gut-microbiota interactions, type of infecting agent, and host-genetic susceptibility are risk factors but also are reasons for the varying spectrum of clinical severity. Although prognosis is generally good, symptoms and inflammation may persist for a long time. Symptomatic relief with antidiarrheals, antispasmodics, 5HT3 antagonists, mesalamine, probiotics, and low-dose antidepressants remain the primary approaches, but in some difficult cases, a combination of drugs that target the pathophysiology may be helpful. PI-IBS has many overlapping features with IBS-D and shares similar pathophysiology and management approaches.
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Affiliation(s)
- Yeong Yeh Lee
- School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia
| | | | - Satish S C Rao
- Section of Gastroenterology/Hepatology, Department of Internal Medicine, Medical College of Georgia, AD 2226, Digestive Health Center, Augusta University, 1481 Laney-Walker Blvd, Augusta, GA, 30912, USA.
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21
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Rabinowicz S, Schwartz E. Morbidity among Israeli paediatric travellers. J Travel Med 2017; 24:4191320. [PMID: 29088478 DOI: 10.1093/jtm/tax062] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2017] [Accepted: 08/15/2017] [Indexed: 11/15/2022]
Abstract
BACKGROUND International travel, particularly to developing countries, is becoming increasingly common among the Israeli population, including an increase in the number of travelling children. Since children are a distinct travellers' population, data about their post-travel morbidity are needed. METHODS A retrospective study which examined all children (0-19 years old) who presented to our centre after international travel from 1999 to 2015. RESULTS About 314 children were seen. The mean age was 10 years (SD ± 5.8). Most of the patients (80.6%) were tourists, and the rest were expatriates. The main destinations visited were South-Asia (46.5%), Sub-Saharan Africa (33.4%), Latin-America (7%) and Europe (6.4%). Overall, the most common diagnoses were gastrointestinal (GI) (mainly chronic) disorders (30.6%), followed by febrile diseases (26.4%), among which 18.1% of patients were diagnosed with dengue fever and 12% with malaria. Dermatologic conditions accounted for 25.2%. Additional diagnoses were schistosomiasis (6.4%) and neuropsychiatric symptoms (2.2%). A substantial part, 10.8%, had eosinophilia, either symptomatic or asymptomatic. Travellers to Asia, compared to travellers to Africa, presented more commonly with GI illness (OR 2.02, 95% confidence interval 1.13-3.61), and dermatologic conditions (OR 1.94, 95% confidence interval 1.05-3.61). Morbidity was associated with a variety of transmission modes, such as food-borne illnesses (30.9%), bite and sting wounds (10.2%), mosquito-borne infections (8%), freshwater contact (6.7%) and tick-borne infections (2.2%). CONCLUSION The main conditions seen in paediatric returning travellers were GI, febrile and dermatologic illnesses, some may be rare in their country of origin. Targeting care for the suspected pathogens based on updated knowledge of epidemiology and thorough travel history is essential.
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Affiliation(s)
- Shira Rabinowicz
- Department of Pediatrics A, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Ramat Gan, Tel Hashomer 5262000, Israel.,Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 6997801, Israel
| | - Eli Schwartz
- Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 6997801, Israel.,The Center for Geographic Medicine and Tropical Diseases, Sheba Medical Center, Ramat Gan, Tel Hashomer 5262000, Israel
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22
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Post-infectious IBS, tropical sprue and small intestinal bacterial overgrowth: the missing link. Nat Rev Gastroenterol Hepatol 2017; 14:435-441. [PMID: 28513629 DOI: 10.1038/nrgastro.2017.37] [Citation(s) in RCA: 49] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Evidence is emerging that IBS, a hitherto enigmatic disorder thought to be predominantly related to psychological factors, has a microorganic basis in a subset of patients with the disease. Post-infectious IBS (PI-IBS), commonly of the diarrhoea-predominant subtype (defined as new development of IBS following acute infectious diarrhoea), is one such condition known to occur in up to 10-30% individuals after acute gastroenteritis. However, following acute infectious gastroenteritis, patients can also develop post-infectious malabsorption syndrome (PI-MAS), popularly known as tropical sprue. As no study on PI-IBS has rigorously excluded tropical sprue by appropriate investigations, including small intestinal biopsy, the frequency of tropical sprue among patients with PI-IBS is not known. Small intestinal bacterial overgrowth (SIBO) has been suggested to be associated with IBS in general, and in particular diarrhoea-predominant IBS, including PI-IBS. SIBO is also known to be associated with tropical sprue. As both IBS, particularly the subset probably associated with SIBO, and tropical sprue improve with antibiotic treatment, we provide evidence and an explanatory model to support a link among these disorders.
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23
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Rezaie A, Park SC, Morales W, Marsh E, Lembo A, Kim JH, Weitsman S, Chua KS, Barlow GM, Pimentel M. Assessment of Anti-vinculin and Anti-cytolethal Distending Toxin B Antibodies in Subtypes of Irritable Bowel Syndrome. Dig Dis Sci 2017; 62:1480-1485. [PMID: 28451914 DOI: 10.1007/s10620-017-4585-z] [Citation(s) in RCA: 35] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2017] [Accepted: 04/18/2017] [Indexed: 12/11/2022]
Abstract
BACKGROUND Antibodies to cytolethal distending toxin B (CdtB) and vinculin are novel biomarkers that rule-in and differentiate irritable bowel syndrome with diarrhea (IBS-D) from other causes of diarrhea and healthy controls. AIM To determine whether these antibodies can also diagnose and differentiate other IBS subtypes. METHODS Subjects with IBS-D based on Rome III criteria (n = 2375) were recruited from a large-scale multicenter clinical trial (TARGET 3). Healthy subjects without gastrointestinal (GI) diseases or symptoms (n = 43) and subjects with mixed IBS (IBS-M) (n = 25) or IBS with constipation (IBS-C) (n = 30) were recruited from two major medical centers. Plasma levels of anti-CdtB and anti-vinculin antibodies in all subjects were determined by enzyme-linked immunosorbent assay. Optical densities of ≥1.68 and ≥2.80 were considered positive for anti-vinculin and anti-CdtB, respectively. Plasma levels of anti-CdtB and anti-vinculin antibodies were highest in IBS-D and lowest in IBS-C and healthy controls (P < 0.001). Levels in IBS-C subjects were not statistically different from controls (P > 0.1). Positivity for anti-CdtB or anti-vinculin resulted in a statistically significant negative gradient from IBS-D (58.1%) to IBS-M (44.0%), IBS-C (26.7%), and controls (16.3%) (P < 0.001). CONCLUSIONS Anti-CdtB and anti-vinculin titers and positivity rates differ in IBS subtypes, with higher antibody levels and positivity rates in IBS-D and IBS-M, and lower levels in IBS-C subjects that are similar to those in healthy controls. These antibodies appear useful in the diagnosis of IBS-M and IBS-D, but not IBS-C. Furthermore, these findings suggest that IBS-C is pathophysiologically distinct from subtypes with diarrheal components (i.e., IBS-M and IBS-D).
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Affiliation(s)
- Ali Rezaie
- GI Motility Program, Division of Gastroenterology, Department of Medicine, Cedars-Sinai Medical Center, 8730 Alden Drive, Thalians Bldg, #E226, Los Angeles, CA, 90048, USA.
| | - Sung Chul Park
- GI Motility Program, Division of Gastroenterology, Department of Medicine, Cedars-Sinai Medical Center, 8730 Alden Drive, Thalians Bldg, #E226, Los Angeles, CA, 90048, USA.,Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon, South Korea
| | - Walter Morales
- GI Motility Program, Division of Gastroenterology, Department of Medicine, Cedars-Sinai Medical Center, 8730 Alden Drive, Thalians Bldg, #E226, Los Angeles, CA, 90048, USA
| | - Emily Marsh
- GI Motility Program, Division of Gastroenterology, Department of Medicine, Cedars-Sinai Medical Center, 8730 Alden Drive, Thalians Bldg, #E226, Los Angeles, CA, 90048, USA
| | - Anthony Lembo
- Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Jae Hak Kim
- Department of Internal Medicine, Dongguk University Ilsan Hospital, The Graduate School of Dongguk University, Goyang, South Korea
| | - Stacy Weitsman
- GI Motility Program, Division of Gastroenterology, Department of Medicine, Cedars-Sinai Medical Center, 8730 Alden Drive, Thalians Bldg, #E226, Los Angeles, CA, 90048, USA
| | - Kathleen S Chua
- GI Motility Program, Division of Gastroenterology, Department of Medicine, Cedars-Sinai Medical Center, 8730 Alden Drive, Thalians Bldg, #E226, Los Angeles, CA, 90048, USA
| | - Gillian M Barlow
- GI Motility Program, Division of Gastroenterology, Department of Medicine, Cedars-Sinai Medical Center, 8730 Alden Drive, Thalians Bldg, #E226, Los Angeles, CA, 90048, USA
| | - Mark Pimentel
- GI Motility Program, Division of Gastroenterology, Department of Medicine, Cedars-Sinai Medical Center, 8730 Alden Drive, Thalians Bldg, #E226, Los Angeles, CA, 90048, USA
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Klem F, Wadhwa A, Prokop L, Sundt W, Farrugia G, Camilleri M, Singh S, Grover M. Prevalence, Risk Factors, and Outcomes of Irritable Bowel Syndrome After Infectious Enteritis: A Systematic Review and Meta-analysis. Gastroenterology 2017; 152:1042-1054.e1. [PMID: 28069350 PMCID: PMC5367939 DOI: 10.1053/j.gastro.2016.12.039] [Citation(s) in RCA: 306] [Impact Index Per Article: 38.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2016] [Revised: 12/29/2016] [Accepted: 12/30/2016] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS Foodborne illness affects 15% of the US population each year, and is a risk factor for irritable bowel syndrome (IBS). We evaluated risk of, risk factors for, and outcomes of IBS after infectious enteritis. METHODS We performed a systematic review of electronic databases from 1994 through August 31, 2015 to identify cohort studies of the prevalence of IBS 3 months or more after infectious enteritis. We used random-effects meta-analysis to calculate the summary point prevalence of IBS after infectious enteritis, as well as relative risk (compared with individuals without infectious enteritis) and host- and enteritis-related risk factors. RESULTS We identified 45 studies, comprising 21,421 individuals with enteritis, followed for 3 months to 10 years for development of IBS. The pooled prevalence of IBS at 12 months after infectious enteritis was 10.1% (95% confidence interval [CI], 7.2-14.1) and at more than 12 months after infectious enteritis was 14.5% (95% CI, 7.7-25.5). Risk of IBS was 4.2-fold higher in patients who had infectious enteritis in the past 12 months than in those who had not (95% CI, 3.1-5.7); risk of IBS was 2.3-fold higher in individuals who had infectious enteritis more than 12 months ago than in individuals who had not (95% CI, 1.8-3.0). Of patients with enteritis caused by protozoa or parasites, 41.9% developed IBS, and of patients with enteritis caused by bacterial infection, 13.8% developed IBS. Risk of IBS was significantly increased in women (odds ratio [OR], 2.2; 95% CI, 1.6-3.1) and individuals with antibiotic exposure (OR, 1.7; 95% CI, 1.2-2.4), anxiety (OR, 2; 95% CI, 1.3-2.9), depression (OR, 1.5; 95% CI, 1.2-1.9), somatization (OR, 4.1; 95% CI, 2.7-6.0), neuroticism (OR, 3.3; 95% CI, 1.6-6.5), and clinical indicators of enteritis severity. There was a considerable level of heterogeneity among studies. CONCLUSIONS In a systematic review and meta-analysis, we found >10% of patients with infectious enteritis develop IBS later; risk of IBS was 4-fold higher than in individuals who did not have infectious enteritis, although there was heterogeneity among studies analyzed. Women-particularly those with severe enteritis-are at increased risk for developing IBS, as are individuals with psychological distress and users of antibiotics during the enteritis.
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Affiliation(s)
- Fabiane Klem
- Division of Gastroenterology & Hepatology, Mayo Clinic, Rochester, MN,Universidade Federal do Paraná, Curitiba, Paraná, Brazil
| | - Akhilesh Wadhwa
- Division of Gastroenterology & Hepatology, Mayo Clinic, Rochester, MN
| | - Larry Prokop
- Division of Gastroenterology & Hepatology, Mayo Clinic, Rochester, MN
| | - Wendy Sundt
- Division of Gastroenterology & Hepatology, Mayo Clinic, Rochester, MN
| | - Gianrico Farrugia
- Division of Gastroenterology & Hepatology, Mayo Clinic, Rochester, MN
| | - Michael Camilleri
- Division of Gastroenterology & Hepatology, Mayo Clinic, Rochester, MN
| | - Siddharth Singh
- Division of Gastroenterology, University of California San Diego, San Diego, CA
| | - Madhusudan Grover
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.
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25
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DuPont HL, Steffen R. Use of antimicrobial agents for treatment and prevention of travellers' diarrhoea in the face of enhanced risk of transient fecal carriage of multi-drug resistant enterobacteriaceae: setting the stage for consensus recommendations. J Travel Med 2017; 24:S57-S62. [PMID: 28881862 DOI: 10.1093/jtm/tax040] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2016] [Accepted: 07/14/2016] [Indexed: 01/08/2023]
Abstract
BACKGROUND The recommendation that antibiotics should be used for routine therapy of travellers' diarrhoea is being reconsidered in view of growing evidence that the therapy may lead to intestinal carriage of multi-drug resistant (MDR) colonic microbiota. This review attempts to put the issues of therapy and MDR acquisition in perspective to help in the establishment of therapeutic recommendations for travellers' diarrhoea. METHODS The existing literature showing the risk and consequences of acquisition of MDR microbiota in antibiotic-treated travellers was reviewed. Issues important to the development of firm evidence-based recommendations for antibiotics use for treatment and prevention of travellers' diarrhoea were researched. RESULTS Six areas of research needed to allow the development of evidence-based recommendations for antibiotic-treatment and -prevention of travellers' diarrhoea were identified. CONCLUSIONS Increasing worldwide occurrence of antibiotic resistance should alert public health officials of the importance of encouraging local antibiotic stewardship guidelines. Six areas to research are identified in this review to allow the development of evidence-based recommendations for use of antibiotics for treatment and selective prevention of travellers' diarrhoea. An interdisciplinary ISTM Consensus group will consider the data available and develop current recommendations for therapy and chemoprevention of travellers' diarrhoea considering groups who would benefit the most from antimicrobials while recognizing the hazards associated with broad use of these drugs. With interim recommendations and ultimately evidence-based recommendations, guidelines can be developed for management of travellers' diarrhoea considering populations and destinations.
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Affiliation(s)
- Herbert L DuPont
- University of Texas School of Public Health.,University of Texas Medical School.,Kelsey Research Foundation.,Baylor College of Medicine, USA, Houston TX, USA
| | - Robert Steffen
- Department of Epidemiology, The University of Zurich, Biostatistics and Prevention Institute, Zurich, Switzerland
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Pathogens of Food Animals: Sources, Characteristics, Human Risk, and Methods of Detection. ADVANCES IN FOOD AND NUTRITION RESEARCH 2017; 82:277-365. [PMID: 28427535 DOI: 10.1016/bs.afnr.2016.12.009] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Pathogens associated with food production (livestock) animals come in many forms causing a multitude of disease for humans. For the purpose of this review, these infectious agents can be divided into three broad categories: those that are associated with bacterial disease, those that are associated with viruses, and those that are parasitic in nature. The goal of this chapter is to provide the reader with an overview of the most common pathogens that cause disease in humans through exposure via the food chain and the consequence of this exposure as well as risk and detection methods. We have also included a collection of unusual pathogens that although rare have still caused disease, and their recognition is warranted in light of emerging and reemerging diseases. These provide the reader an understanding of where the next big outbreak could occur. The influence of the global economy, the movement of people, and food makes understanding production animal-associated disease paramount to being able to address new diseases as they arise.
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27
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Food-Borne Diarrheal Illness. Infect Dis (Lond) 2017. [DOI: 10.1016/b978-0-7020-6285-8.00037-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
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28
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Tseng A, Herrick T. Health Care of the International Traveler. Fam Med 2017. [DOI: 10.1007/978-3-319-04414-9_9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
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29
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Wang HB, Mo QH, Wang Q, Wu BM, Feng ZL, Lin JC, Yang Z. Probe-free and sensitive detection of diarrhea-causing pathogens using RT-PCR combined high resolution melting analysis. Biologicals 2016; 44:360-6. [DOI: 10.1016/j.biologicals.2016.06.012] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2015] [Revised: 06/24/2016] [Accepted: 06/29/2016] [Indexed: 11/29/2022] Open
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30
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Connor BA. Post-Infectious Sequelae of Travelers’ Diarrhea: Reactive Arthritis, Guillain-Barré Syndrome, and Irritable Bowel Syndrome. CURRENT TROPICAL MEDICINE REPORTS 2016. [DOI: 10.1007/s40475-016-0080-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
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31
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Lääveri T, Sterne J, Rombo L, Kantele A. Systematic review of loperamide: No proof of antibiotics being superior to loperamide in treatment of mild/moderate travellers' diarrhoea. Travel Med Infect Dis 2016; 14:299-312. [PMID: 27363327 DOI: 10.1016/j.tmaid.2016.06.006] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2016] [Revised: 06/19/2016] [Accepted: 06/20/2016] [Indexed: 12/18/2022]
Abstract
Looking at the worldwide emergency of antimicrobial resistance, international travellers appear to have a central role in spreading the bacteria across the globe. Travellers' diarrhoea (TD) is the most common disease encountered by visitors to the (sub)tropics. Both TD and its treatment with antibiotics have proved significant independent risk factors of colonization by resistant intestinal bacteria while travelling. Travellers should therefore be given preventive advice regarding TD and cautioned about taking antibiotics: mild or moderate TD does not require antibiotics. Logical alternatives are medications with effects on gastrointestinal function, such as loperamide. The present review explores literature on loperamide in treating TD. Adhering to manufacturer's dosage recommendations, loperamide offers a safe and effective alternative for relieving mild and moderate symptoms. Moreover, loperamide taken singly does no predispose to contracting MDR bacteria. Most importantly, we found no proof that would show antibiotics to be significantly more effective than loperamide in treating mild/moderate TD.
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Affiliation(s)
- Tinja Lääveri
- Inflammation Center, Division of Infectious Diseases, University of Helsinki and Helsinki University Hospital, Helsinki, POB 348, FIN-00029 HUS, Finland.
| | - Jesper Sterne
- Centre for Clinical Research, Sörmland County Council, Eskilstuna and University of Uppsala, SE 631 88 Eskilstuna, Sweden.
| | - Lars Rombo
- Centre for Clinical Research, Sörmland County Council, Eskilstuna and University of Uppsala, SE 631 88 Eskilstuna, Sweden; Karolinska Institutet, Department of Medicine/Solna, Unit for Infectious Diseases, SE 17176 Stockholm, Sweden.
| | - Anu Kantele
- Inflammation Center, Division of Infectious Diseases, University of Helsinki and Helsinki University Hospital, Helsinki, POB 348, FIN-00029 HUS, Finland; Karolinska Institutet, Department of Medicine/Solna, Unit for Infectious Diseases, SE 17176 Stockholm, Sweden; Department of Medicine, University of Helsinki, Finland.
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32
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DuPont HL, Steffen R. Use of antimicrobial agents for treatment and prevention of travellers' diarrhoea in the face of enhanced risk of transient fecal carriage of multi-drug resistant enterobacteriaceae: setting the stage for consensus recommendations. J Travel Med 2016; 23:taw054. [PMID: 27503854 DOI: 10.1093/jtm/taw054] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2016] [Accepted: 07/14/2016] [Indexed: 12/11/2022]
Abstract
BACKGROUND The recommendation that antibiotics should be used for routine therapy of travellers' diarrhoea is being reconsidered in view of growing evidence that the therapy may lead to intestinal carriage of multi-drug resistant (MDR) colonic microbiota. This review attempts to put the issues of therapy and MDR acquisition in perspective to help in the establishment of therapeutic recommendations for travellers' diarrhoea. METHODS The existing literature showing the risk and consequences of acquisition of MDR microbiota in antibiotic-treated travellers was reviewed. Issues important to the development of firm evidence-based recommendations for antibiotics use for treatment and prevention of travellers' diarrhoea were researched. RESULTS Six areas of research needed to allow the development of evidence-based recommendations for antibiotic-treatment and -prevention of travellers' diarrhoea were identified. CONCLUSIONS Increasing worldwide occurrence of antibiotic resistance should alert public health officials of the importance of encouraging local antibiotic stewardship guidelines. Six areas to research are identified in this review to allow the development of evidence-based recommendations for use of antibiotics for treatment and selective prevention of travellers' diarrhoea. An interdisciplinary ISTM Consensus group will consider the data available and develop current recommendations for therapy and chemoprevention of travellers' diarrhoea considering groups who would benefit the most from antimicrobials while recognizing the hazards associated with broad use of these drugs. With interim recommendations and ultimately evidence-based recommendations, guidelines can be developed for management of travellers' diarrhoea considering populations and destinations.
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Affiliation(s)
- Herbert L DuPont
- University of Texas School of Public Health University of Texas Medical School Kelsey Research Foundation Baylor College of Medicine, USA, Houston TX, USA
| | - Robert Steffen
- Department of Epidemiology, The University of Zurich, Biostatistics and Prevention Institute, Zurich, Switzerland
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33
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Schwille-Kiuntke J, Enck P, Polster AV, Gaile M, Kremsner PG, Zanger P. Postinfectious irritable bowel syndrome after travelers' diarrhea--a cohort study. Neurogastroenterol Motil 2015; 27:1147-55. [PMID: 26009981 DOI: 10.1111/nmo.12601] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2015] [Accepted: 04/24/2015] [Indexed: 12/19/2022]
Abstract
BACKGROUND There is sound evidence for the role of gastrointestinal infections in the development of postinfectious irritable bowel syndrome (PI-IBS), but understanding the interaction between mental factors and the infection remains incomplete. This study aims to (i) assess the occurrence of PI-IBS in a cohort of patients with self-reported travelers' diarrhea (TD), (ii) assess risk factors for PI-IBS development, and (iii) investigate the prognosis of PI-IBS after 1 year. METHODS Patients consulting the travel clinic at the University Hospital Tuebingen, Germany (in 2009 and 2010) were identified from records and questioned in follow-ups in 2011 and 2012. We used the Rome III modular questionnaire to assess IBS, the Hospital Anxiety and Depression Scale to assess anxiety and depression, and the Patient Health Questionnaire to assess somatization. KEY RESULTS We identified 529 eligible subjects from the clinical records. Of 135 subjects (age: 36.6 ± 14.6 years, 58.5% female) included in the study sample 6.7% (95% CI 3.0-11.1) had PI-IBS. We found more females (88.9% vs 56.3%, p = 0.08) and younger age subjects (mean 29.3 vs 37.1 years, p = 0.02) among the PI-IBS subjects. A multivariable regression model revealed vomiting at baseline and high somatization scores as strong and independent PI-IBS risk factors. One year later PI-IBS occurrence decreased to 3.3% (three cases of 90). CONCLUSIONS & INFERENCES Our findings underline the close linkage of mental and somatic processes for the manifestation of PI-IBS. Screening for psychiatric comorbidities in patients with severe gastrointestinal infections may allow identifying groups at high risk for PI-IBS.
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Affiliation(s)
- J Schwille-Kiuntke
- Department of Internal Medicine VI: Psychosomatic Medicine and Psychotherapy, University Hospital Tübingen, Tübingen, Germany
| | - P Enck
- Department of Internal Medicine VI: Psychosomatic Medicine and Psychotherapy, University Hospital Tübingen, Tübingen, Germany
| | - A V Polster
- Department of Internal Medicine VI: Psychosomatic Medicine and Psychotherapy, University Hospital Tübingen, Tübingen, Germany.,Department of Internal Medicine, University of Gothenburg, Gothenburg, Sweden
| | - M Gaile
- Department of Internal Medicine VII: Institute of Tropical Medicine, University Hospital Tübingen, Tübingen, Germany
| | - P G Kremsner
- Department of Internal Medicine VII: Institute of Tropical Medicine, University Hospital Tübingen, Tübingen, Germany
| | - P Zanger
- Department of Internal Medicine VII: Institute of Tropical Medicine, University Hospital Tübingen, Tübingen, Germany.,Institute of Public Health, University Hospital Heidelberg, Heidelberg, Germany
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34
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Kaakoush NO, Castaño-Rodríguez N, Mitchell HM, Man SM. Global Epidemiology of Campylobacter Infection. Clin Microbiol Rev 2015; 28:687-720. [PMID: 26062576 PMCID: PMC4462680 DOI: 10.1128/cmr.00006-15] [Citation(s) in RCA: 953] [Impact Index Per Article: 95.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Campylobacter jejuni infection is one of the most widespread infectious diseases of the last century. The incidence and prevalence of campylobacteriosis have increased in both developed and developing countries over the last 10 years. The dramatic increase in North America, Europe, and Australia is alarming, and data from parts of Africa, Asia, and the Middle East indicate that campylobacteriosis is endemic in these areas, especially in children. In addition to C. jejuni, there is increasing recognition of the clinical importance of emerging Campylobacter species, including Campylobacter concisus and Campylobacter ureolyticus. Poultry is a major reservoir and source of transmission of campylobacteriosis to humans. Other risk factors include consumption of animal products and water, contact with animals, and international travel. Strategic implementation of multifaceted biocontrol measures to reduce the transmission of this group of pathogens is paramount for public health. Overall, campylobacteriosis is still one of the most important infectious diseases that is likely to challenge global health in the years to come. This review provides a comprehensive overview of the global epidemiology, transmission, and clinical relevance of Campylobacter infection.
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Affiliation(s)
- Nadeem O Kaakoush
- School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, NSW, Australia
| | - Natalia Castaño-Rodríguez
- School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, NSW, Australia
| | - Hazel M Mitchell
- School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, NSW, Australia
| | - Si Ming Man
- School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, NSW, Australia Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA
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35
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Schwille-Kiuntke J, Mazurak N, Enck P. Systematic review with meta-analysis: post-infectious irritable bowel syndrome after travellers' diarrhoea. Aliment Pharmacol Ther 2015; 41:1029-37. [PMID: 25871571 DOI: 10.1111/apt.13199] [Citation(s) in RCA: 77] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/17/2014] [Revised: 12/11/2014] [Accepted: 03/25/2015] [Indexed: 01/06/2023]
Abstract
BACKGROUND Gastrointestinal infection is known as a risk factor for the development of the irritable bowel syndrome (post-infectious irritable bowel syndrome, PI-IBS). The incidence of PI-IBS ranges between 3% and over 30% of people after infectious gastroenteritis. AIM To perform a meta-analysis pools and report data concerning the relative risk (RR) of PI-IBS after TD. METHODS Database search using Medline through PubMed, Scopus, EBM Reviews (Cochrane Database of Systematic Reviews) and PsycINFO was performed to identify relevant studies. Those that met the inclusion criteria were pooled. A random effects model (Mantel-Haenszel) was performed. RESULTS Six eligible studies were found. In three of six studies, the authors reported a statistically significant association of TD and PI-IBS. The pooled RR was 3.35 (95% CI: 2.22-5.05) with a significant overall effect (P < 0.00001). Overall PI-IBS incidence was 5.4% in TD subjects and 1.4% in healthy subjects. There was no significant heterogeneity within the pooled studies (I(2) = 5%). Self-reported TD alone resulted in an over 1.5-fold RR for PI-IBS compared to laboratory-confirmed TD [RR 3.90 (95% CI: 2.35-6.49) vs. RR 2.42 (95% CI: 1.22-4.78)]. CONCLUSIONS There is a strong association between travellers' diarrhoea and post-infectious irritable bowel syndrome. Self-reports of exposure seem to result in a higher post-infectious irritable bowel syndrome occurrence than laboratory-confirmed cases of travellers' diarrhoea, but further studies are needed to confirm this finding. Finally, potential influences of the selection of an appropriate study population on post-infectious irritable bowel syndrome epidemiology are discussed.
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Affiliation(s)
- J Schwille-Kiuntke
- Department of Internal Medicine VI: Psychosomatic Medicine and Psychotherapy, University Hospital Tuebingen, Tuebingen, Germany
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36
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Bijvelds MJC, Loos M, Bronsveld I, Hellemans A, Bongartz JP, Ver Donck L, Cox E, de Jonge HR, Schuurkes JAJ, De Maeyer JH. Inhibition of Heat-Stable Toxin-Induced Intestinal Salt and Water Secretion by a Novel Class of Guanylyl Cyclase C Inhibitors. J Infect Dis 2015; 212:1806-15. [PMID: 25999056 DOI: 10.1093/infdis/jiv300] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2015] [Accepted: 05/13/2015] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND Many enterotoxigenic Escherichia coli strains produce the heat-stable toxin, STa, which, by activation of the intestinal receptor-enzyme guanylyl cyclase (GC) C, triggers an acute, watery diarrhea. We set out to identify GCC inhibitors that may be of benefit for the treatment of infectious diarrheal disease. METHODS Compounds that inhibit STa-induced cyclic guanosine 3',5'-monophosphate (cGMP) production were selected by performing cyclase assays on cells and membranes containing GCC, or the related GCA. The effect of leads on STa/GCC-dependent activation of the cystic fibrosis transmembrane conductance regulator anion channel was investigated in T84 cells, and in porcine and human intestinal tissue. Their effect on STa-provoked fluid transport was assessed in ligated intestinal loops in piglets. RESULTS Four N-2-(propylamino)-6-phenylpyrimidin-4-one-substituted piperidines were shown to inhibit GCC-mediated cellular cGMP production. The half maximal inhibitory concentrations were ≤ 5 × 10(-7) mol/L, whereas they were >10 times higher for GCA. In T84 monolayers, these leads blocked STa/GCC-dependent, but not forskolin/adenylyl cyclase-dependent, cystic fibrosis transmembrane conductance regulator activity. GCC inhibition reduced STa-provoked anion secretion in pig jejunal tissue, and fluid retention and cGMP levels in STa-exposed loops. These GCC inhibitors blocked STa-provoked anion secretion in rectal biopsy specimens. CONCLUSIONS We have identified a novel class of GCC inhibitors that may form the basis for development of future therapeutics for (infectious) diarrheal disease.
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Affiliation(s)
- Marcel J C Bijvelds
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands
| | - Michaela Loos
- Laboratory of Immunology, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
| | - Inez Bronsveld
- Department of Pulmonology, University Medical Center Utrecht, The Netherlands
| | | | | | - Luc Ver Donck
- Janssen Research and Development, Janssen Pharmaceutica NV, Beerse, Belgium
| | - Eric Cox
- Laboratory of Immunology, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
| | - Hugo R de Jonge
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands
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Development and validation of a biomarker for diarrhea-predominant irritable bowel syndrome in human subjects. PLoS One 2015; 10:e0126438. [PMID: 25970536 PMCID: PMC4430499 DOI: 10.1371/journal.pone.0126438] [Citation(s) in RCA: 100] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2015] [Accepted: 04/02/2015] [Indexed: 02/07/2023] Open
Abstract
Diarrhea-predominant irritable bowel syndrome (IBS) is diagnosed through clinical criteria after excluding “organic” conditions, and can be precipitated by acute gastroenteritis. Cytolethal distending toxin B (CdtB) is produced by bacteria that cause acute gastroenteritis, and a post-infectious animal model demonstrates that host antibodies to CdtB cross-react with vinculin in the host gut, producing an IBS-like phenotype. Therefore, we assessed circulating anti-CdtB and anti-vinculin antibodies as biomarkers for D-IBS in human subjects. Subjects with D-IBS based on Rome criteria (n=2375) were recruited from a large-scale multicenter clinical trial for D-IBS (TARGET 3). Subjects with inflammatory bowel disease (IBD) (n=142), subjects with celiac disease (n=121), and healthy controls (n=43) were obtained for comparison. Subjects with IBD and celiac disease were recruited based on the presence of intestinal complaints and histologic confirmation of chronic inflammatory changes in the colon or small intestine. Subjects with celiac disease were also required to have an elevated tTG and biopsy. All subjects were aged between 18 and 65 years. Plasma levels of anti-CdtB and anti-vinculin antibodies were determined by ELISA, and compared between groups. Anti-CdtB titers were significantly higher in D-IBS subjects compared to IBD, healthy controls and celiac disease (P<0.001). Anti-vinculin titers were also significantly higher in IBS (P<0.001) compared to the other groups. The area-under-the-receiver operating curves (AUCs) were 0.81 and 0.62 for diagnosis of D-IBS against IBD for anti-CdtB and anti-vinculin, respectively. Both tests were less specific in differentiating IBS from celiac disease. Optimization demonstrated that for anti-CdtB (optical density≥2.80) the specificity, sensitivity and likelihood ratio were 91.6%, 43.7 and 5.2, respectively, and for anti-vinculin (OD≥1.68) were 83.8%, 32.6 and 2.0, respectively. These results confirm that anti-CdtB and anti-vinculin antibodies are elevated in D-IBS compared to non-IBS subjects. These biomarkers may be especially helpful in distinguishing D-IBS from IBD in the workup of chronic diarrhea.
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Pimentel M, Morales W, Pokkunuri V, Brikos C, Kim SM, Kim SE, Triantafyllou K, Weitsman S, Marsh Z, Marsh E, Chua KS, Srinivasan S, Barlow GM, Chang C. Autoimmunity Links Vinculin to the Pathophysiology of Chronic Functional Bowel Changes Following Campylobacter jejuni Infection in a Rat Model. Dig Dis Sci 2015; 60:1195-1205. [PMID: 25424202 DOI: 10.1007/s10620-014-3435-5] [Citation(s) in RCA: 61] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2014] [Accepted: 11/11/2014] [Indexed: 02/06/2023]
Abstract
BACKGROUND Acute gastroenteritis can precipitate irritable bowel syndrome (IBS) in humans. Cytolethal distending toxin is common to all pathogens causing gastroenteritis. Its active subunit, CdtB, is associated with post-infectious bowel changes in a rat model of Campylobacter jejuni infection, including small intestinal bacterial overgrowth (SIBO). AIM To evaluate the role of host antibodies to CdtB in contributing to post-infectious functional sequelae in this rat model. METHODS Ileal tissues from non-IBS human subjects, C. jejuni-infected and control rats were immunostained with antibodies to CdtB, c-Kit, S-100, PGP 9.5 and vinculin. Cytosolic and membrane proteins from mouse enteric neuronal cell lysates were immunoprecipitated with anti-CdtB and analyzed by mass spectrometry. ELISAs were performed on rat cardiac serum using CdtB or vinculin as antigens. RESULTS Anti-CdtB antibodies bound to a cytosolic protein in interstitial cells of Cajal (ICC) and myenteric ganglia in C. jejuni-infected and naïve rats and human subjects. Mass spectrometry identified vinculin, confirmed by co-localization and ELISAs. Anti-CdtB antibodies were higher in C. jejuni-infected rats (1.27 ± 0.15) than controls (1.76 ± 0.12) (P < 0.05), and rats that developed SIBO (2.01 ± 0.18) vs. rats that did not (1.44 ± 0.11) (P = 0.019). Vinculin expression levels were reduced in C. jejuni-infected rats (0.058 ± 0.053) versus controls (0.087 ± 0.023) (P = 0.0001), with greater reductions in rats with two C. jejuni infections (P = 0.0001) and rats that developed SIBO (P = 0.001). CONCLUSIONS Host anti-CdtB antibodies cross-react with vinculin in ICC and myenteric ganglia, required for normal gut motility. Circulating antibody levels and loss of vinculin expression correlate with number of C. jejuni exposures and SIBO, suggesting that effects on vinculin are important in the effects of C. jejuni infection on the host gut.
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Affiliation(s)
- Mark Pimentel
- GI Motility Program, Division of Gastroenterology, Cedars-Sinai Medical Center, 8730 Alden Drive, Suite 225E, Los Angeles, CA, 90048, USA,
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Lalani T, Maguire JD, Grant EM, Fraser J, Ganesan A, Johnson MD, Deiss RG, Riddle MS, Burgess T, Tribble DR. Epidemiology and self-treatment of travelers' diarrhea in a large, prospective cohort of department of defense beneficiaries. J Travel Med 2015; 22:152-60. [PMID: 25483360 PMCID: PMC4409454 DOI: 10.1111/jtm.12179] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2014] [Revised: 09/25/2014] [Accepted: 10/06/2014] [Indexed: 01/26/2023]
Abstract
BACKGROUND Infectious diarrhea is a common problem among travelers. Expert guidelines recommend the prompt use of antibiotics for self-treatment of moderate or severe travelers' diarrhea (TD). There is limited data on whether travelers follow these self-treatment guidelines. We evaluated the risk factors associated with TD, the use of TD self-treatment, and the risk of irritable bowel syndrome (IBS) during travel. METHODS Department of Defense beneficiaries traveling outside the United States for ≤6.5 months were enrolled in a prospective cohort study. Participants received pre- and post-travel surveys, and could opt into a travel illness diary and follow-up surveys for symptoms of IBS. Standard definitions were used to assess for TD and IBS. Suboptimal self-treatment was defined as the use of antibiotics (with or without antidiarrheal agents) for mild TD, or the use of antidiarrheals alone or no self-treatment in cases of moderate or severe TD. RESULTS Twenty-four percent of participants (270/1,120) met the criteria for TD. The highest incidence was recorded in Africa [8.6 cases/100 person-weeks, 95% confidence interval (CI): 6.7-10.5]. Two hundred and twelve participants with TD provided information regarding severity and self-treatment: 89 (42%) had mild TD and 123 (58%) had moderate or severe TD. Moderate or severe TD was independently associated with suboptimal self-treatment [OR 10.4 (95% CI: 4.92-22.0)]. Time to last unformed stool did not differ between optimal and suboptimal self-treatment. IBS occurred in 4.5% (7/154) of TD cases and in 3.1% (16/516) of cases without TD (p = 0.39). Among TD cases, a lower incidence of IBS was noted in participants who took antibiotics [4.8% (5/105) vs 2.2% (1/46)] in those who did not, but the difference did not reach statistical significance (p = 0.60). CONCLUSIONS Our results suggest the underutilization of antibiotics in travelers with moderate or severe TD. Further studies are needed to systematically evaluate pre-travel instruction and traveler adherence to self-treatment guidelines, and the impact of suboptimal self-treatment on outcomes.
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Affiliation(s)
- Tahaniyat Lalani
- Infectious Disease Clinical Research Program, Uniformed Services University of the Health Sciences, Bethesda, MD, USA; Henry M Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA; Division of Infectious Diseases, Naval Medical Center, Portsmouth, VA, USA
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Epidemiology and clinical manifestations of enteroaggregative Escherichia coli. Clin Microbiol Rev 2015; 27:614-30. [PMID: 24982324 DOI: 10.1128/cmr.00112-13] [Citation(s) in RCA: 132] [Impact Index Per Article: 13.2] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Enteroaggregative Escherichia coli (EAEC) represents a heterogeneous group of E. coli strains. The pathogenicity and clinical relevance of these bacteria are still controversial. In this review, we describe the clinical significance of EAEC regarding patterns of infection in humans, transmission, reservoirs, and symptoms. Manifestations associated with EAEC infection include watery diarrhea, mucoid diarrhea, low-grade fever, nausea, tenesmus, and borborygmi. In early studies, EAEC was considered to be an opportunistic pathogen associated with diarrhea in HIV patients and in malnourished children in developing countries. In recent studies, associations with traveler's diarrhea, the occurrence of diarrhea cases in industrialized countries, and outbreaks of diarrhea in Europe and Asia have been reported. In the spring of 2011, a large outbreak of hemolytic-uremic syndrome (HUS) and hemorrhagic colitis occurred in Germany due to an EAEC O104:H4 strain, causing 54 deaths and 855 cases of HUS. This strain produces the potent Shiga toxin along with the aggregative fimbriae. An outbreak of urinary tract infection associated with EAEC in Copenhagen, Denmark, occurred in 1991; this involved extensive production of biofilm, an important characteristic of the pathogenicity of EAEC. However, the heterogeneity of EAEC continues to complicate diagnostics and also our understanding of pathogenicity.
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Abstract
Diarrhoea is probably the single most common medical complaint in returning travellers. The most common pathogens are entero-toxigenic Escherichia coli, Shigella, Salmonella and Campylobacter. Viruses, toxigenic Arcobacter and Bacteroides fragilis, as well as parasites such as Cryptosporidium sp, are increasingly recognised but are not tested for in most diagnostic laboratories. Blood in stools is a sign of invasive disease and should trigger exclusion of invasive amoebic disease. The use of empiric antibiotics may shorten illness but is complicated by the diversity of bacterial causes and emerging resistance.
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Affiliation(s)
- Alastair C McGregor
- Hospital for Tropical Diseases, London, UK, and Imported Fever Service, Rare and Imported Pathogens Laboratory, Public Health England, Porton Down, UK
| | - Stephen G Wright
- Hospital for Tropical Diseases, London, UK, and consultant physician, King Edward VII Hospital, London, UK
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Abstract
Tropical sprue (TS), once known to be a common cause of malabsorption syndrome (MAS) in India and other tropical countries, is believed to be uncommon currently in spite of contrary evidence. Several recent studies from India showed TS to be the commonest cause of sporadic MAS in Indian adults. TS is diagnosed in patients presenting with suggestive clinical presentation, which cannot be explained by another cause of MAS and investigations revealing malabsorption of two unrelated substances, abnormal small-intestinal mucosal histology, which responds to treatment with antibiotics such as tetracycline and folic acid. There is substantial overlap between TS and postinfectious irritable bowel syndrome. There have been several advances in epidemiology, pathogenesis, and diagnosis of TS, hitherto an enigmatic condition.
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Nair P, Okhuysen PC, Jiang ZD, Carlin LG, Belkind-Gerson J, Flores J, Paredes M, DuPont HL. Persistent abdominal symptoms in US adults after short-term stay in Mexico. J Travel Med 2014; 21:153-8. [PMID: 24621006 DOI: 10.1111/jtm.12114] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2013] [Revised: 10/22/2013] [Accepted: 11/22/2013] [Indexed: 01/25/2023]
Abstract
BACKGROUND Postinfectious irritable bowel syndrome (PI-IBS) has been reported as a complication of bacterial diarrhea including travelers' diarrhea (TD). This study assessed the role of TD among US students in Mexico in triggering the onset of persistent abdominal symptoms (PAS) and IBS. METHODS We conducted a 6-month follow-up of a cohort of 817 US students in Mexico as short-term study to assess the frequency of PAS and IBS. Using Rome II criteria for IBS, groups of students with PAS were then categorized as PI-IBS if they met the symptom criteria for IBS or as suffering from functional abdominal disorder (FAD) if they did not meet the criteria. RESULTS FAD and IBS were commonly found in US students 6 months after leaving Mexico. Important variables in their development were younger adult age, longer stays in Mexico and occurrence of acute diarrhea while in Mexico. Diarrhea while in Mexico occurred more commonly for those later diagnosed with FAD, 101/196 (52%), relative risk (RR) = 1.5 [confidence interval (CI) 1.2-1.8; p = 0.001]; IBS, 20/32 (63%), RR = 2.5 (CI 1.2-5.0; p = 0.007); and PAS (FAD + IBS), 121/228 (53%), RR = 1.5 (CI 1.2-1.8; p < 0.001) compared with subjects who had experienced diarrhea while in Mexico but were not diagnosed with PAS at 6 months, 227/589 (39%). Diarrhea caused by heat-labile enterotoxin-producing enterotoxigenic Escherichia coli or Providencia ssp. demonstrated a greater risk of developing PAS. CONCLUSIONS PAS occurred commonly in a subset of younger adult travelers who stayed longer in Mexico and experienced acute diarrhea while there. Further studies with this cohort will focus on host genetic associations with the development of PAS.
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Affiliation(s)
- Parvathy Nair
- Division of Epidemiology, Human Genetics and Environmental Sciences, Center for Infectious Disease, The University of Texas School of Public Health, Houston, TX, USA
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Schmulson M, Bielsa MV, Carmona-Sánchez R, Hernández A, López-Colombo A, López Vidal Y, Peláez-Luna M, Remes-Troche JM, Tamayo JL, Valdovinos MA. Microbiota, gastrointestinal infections, low-grade inflammation, and antibiotic therapy in irritable bowel syndrome: an evidence-based review. REVISTA DE GASTROENTEROLOGIA DE MEXICO 2014; 79:96-134. [PMID: 24857420 DOI: 10.1016/j.rgmx.2014.01.004] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/19/2013] [Revised: 01/22/2014] [Accepted: 01/23/2014] [Indexed: 12/16/2022]
Abstract
BACKGROUND Post-infectious irritable bowel syndrome (PI-IBS) prevalence, small intestinal bacterial overgrowth (SIBO), altered microbiota, low-grade inflammation, and antibiotic therapy in IBS are all controversial issues. AIMS To conduct an evidence-based review of these factors. METHODS A review of the literature was carried out up to July 2012, with the inclusion of additional articles as far as August 2013, all of which were analyzed through the Oxford Centre for Evidence-Based Medicine (OCEBM) system. RESULTS 1.There is greater SIBO probability in IBS when breath tests are performed, but prevalence varies widely (2-84%). 2.The gut microbiota in individuals with IBS is different from that in healthy subjects, but a common characteristic present in all the patients has not been established. 3.The incidence and prevalence of PI-IBS varies from 9-10% and 3-17%, respectively, and the latter decreases over time. Bacterial etiology is the most frequent but post-viral and parasitic cases have been reported. 4.A sub-group of patients has increased enterochromaffin cells, intraepithelial lymphocytes, and mast cells in the intestinal mucosa, but no differences between PI-IBS and non-PI-IBS have been determined. 5.Methanogenic microbiota has been associated with IBS with constipation. 6.Rifaximin at doses of 400mg TID/10days or 550mg TID/14days is effective treatment for the majority of overall symptoms and abdominal bloating in IBS. Retreatment effectiveness appears to be similar to that of the first cycle. CONCLUSIONS Further studies are required to determine the nature of the gut microbiota in IBS and the differences in low-grade inflammation between PI-IBS and non-PI-IBS. Rifaximin has shown itself to be effective treatment for IBS, regardless of prior factors.
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Affiliation(s)
- M Schmulson
- Laboratorio de Hígado, Páncreas y Motilidad (HIPAM), Departamento de Medicina Experimental, Facultad de Medicina, Universidad Nacional Autónoma de México (UNAM), Hospital General de México, México DF, México.
| | - M V Bielsa
- Departamento de Gastroenterología, Facultad de Medicina, Universidad Autónoma de Guadalajara, Guadalajara, Jalisco, México
| | - R Carmona-Sánchez
- Servicio de Gastroenterología, Servicio de Medicina Interna, Hospital Ángeles-CMP, San Luis Potosí, San Luis Potosí, México
| | - A Hernández
- Servicio de Endoscopia, Instituto Nacional de Cancerología, México DF, México
| | - A López-Colombo
- Coordinación Delegacional de Investigación en Salud, Instituto Mexicano del Seguro Social, Puebla, Puebla, México
| | - Y López Vidal
- Programa de Inmunología Molecular Microbiana, Departamento de Microbiología y Parasitología, Facultad de Medicina, Universidad Nacional Autónoma de México (UNAM), México DF, México
| | - M Peláez-Luna
- Laboratorio de Hígado, Páncreas y Motilidad (HIPAM), Departamento de Medicina Experimental, Facultad de Medicina, Universidad Nacional Autónoma de México (UNAM), Hospital General de México, México DF, México
| | - J M Remes-Troche
- Laboratorio de Fisiología Digestiva y Motilidad Gastrointestinal, Instituto de Investigaciones Médico-Biológicas, Universidad Veracruzana, Veracruz, Veracruz, México; Facultad de Medicina «Miguel Alemán Valdés», Universidad Veracruzana, Veracruz, Veracruz, México
| | - J L Tamayo
- Centro de Investigación y Docencia en Ciencias de la Salud, Universidad Autónoma de Sinaloa, Hospital Civil de Culiacán, Culiacán, Sinaloa, México
| | - M A Valdovinos
- Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México DF, México
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Schmulson M, Bielsa MV, Carmona-Sánchez R, Hernández A, López-Colombo A, Vidal YL, Peláez-Luna M, Remes-Troche JM, Tamayo JL, Valdovinos MA. Microbiota, gastrointestinal infections, low-grade inflammation, and antibiotic therapy in irritable bowel syndrome (IBS): an evidence-based review. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO (ENGLISH EDITION) 2014. [DOI: 10.1016/j.rgmxen.2014.01.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
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Estrada-Garcia T, Perez-Martinez I, Bernal-Reynaga R, Zaidi MB. Enteroaggregative coli: A Pathogen Bridging the North and South. CURRENT TROPICAL MEDICINE REPORTS 2014; 1:88-96. [PMID: 24892007 DOI: 10.1007/s40475-014-0018-7] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Enteroaggregative Escherichia coli (EAEC) is a heterogeneous emerging enteric pathogen. Identified during the 1980's when EAEC strains where isolated from cases of acute and persistent diarrhea among infants from developing countries and of traveler's diarrhea. Subsequently, EAEC strains were linked with foodborne outbreaks and diarrhea illness in adults and children from industrialized countries, HIV-infected subjects and stunting of malnourished poor children. Nowadays, EAEC is increasingly recognized as a major cause of acute diarrhea in children recurring hospitalization and of traveler's diarrhea worldwide. EAEC strains defining phenotype is the aggregative adherence (AA) pattern on epithelial cells. AggR a transcriptional regulator of several EAEC virulence genes has been a key factor in both understanding EAEC pathogenesis and defining typical EAEC (tEAEC) strains. EAEC virulence genes distribution among these strains is highly variable. Present challenges are the identification of key virulence genes and how they coordinately function in the setting of enteric disease.
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Affiliation(s)
| | | | | | - Mussaret B Zaidi
- Microbiology Research Laboratory and Pediatric Emergency Department, Hospital General O'Horán, Mérida, Yucatán, México ; Infectious Diseases Research Unit, Hospital Regional de Alta Especialidad de La Península de Yucatán, Mérida, Yucatán, México
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Chemotactic chemokines are important in the pathogenesis of irritable bowel syndrome. PLoS One 2014; 9:e93144. [PMID: 24667736 PMCID: PMC3965506 DOI: 10.1371/journal.pone.0093144] [Citation(s) in RCA: 50] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2013] [Accepted: 02/28/2014] [Indexed: 12/13/2022] Open
Abstract
Irritable bowel syndrome (IBS) is one of the most frequently diagnosed disorders, affecting about 20% of the general population in Western countries. This syndrome poses an enormous socio-economic burden, impairs the quality of life substantially, and increases healthcare costs. IBS can be classified as either idiopathic (ID-IBS) with unknown etiology or post-infectious (PI-IBS), which develops after a bout of acute diarrhea or gastroenteritis. Little is known about the immunopathogenesis of these two forms of IBS. We evaluated various biomarkers in clinical samples of ID-IBS and PI-IBS patients with the goal to test the hypothesis that the immunologic presentations of these forms of IBS are similar, despite their apparent different etiologic origins. Sera and stool samples from PI-IBS, ID-IBS, and healthy volunteers were analyzed for relative amounts of 36 different biomarkers using the Proteome Profiler Human Cytokine Array Panel A Kit and quantitative ELISA. Our results demonstrated significantly high levels of chemotactic chemokines monocytes chemotactic protein-1 (CCL2) [p-value = 0.003], macrophage inflammatory protein-1β (CCL4) [p-value = 0.010], and CXCL16 (p-value 0.001) in the sera and stools of both ID-IBS and PI-IBS patients. Furthermore, pro-inflammatory cytokines (IFN-γ, IL-1β, and TNF-α) were significantly higher in IBS patients. Anti-inflammatory cytokines (IL-10, IL-4, and IL-13) were variable except IL-10, which was significantly higher in the healthy volunteers than the IBS patients. Remarkably, the amounts and expression pattern of these biomarkers were not significantly different between ID-IBS and PI-IBS. Thus, ID-IBS and PI-IBS present similar immunologic and clinical phenotypes, in spite of their different etiologic origins.
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Mutsch M, Pitzurra R, Hatz C, Steffen R. Post-infectious sequelae of travelers' diarrhea: irritable bowel syndrome. J Travel Med 2014; 21:141-3. [PMID: 24593027 DOI: 10.1111/jtm.12094_1] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Affiliation(s)
- Margot Mutsch
- Epidemiology of Communicable Diseases, WHO CC for Travellers' Health, University of Zurich, Zurich, Switzerland
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Tseng A, Herrick T. Health Care of the International Traveler. Fam Med 2014. [DOI: 10.1007/978-1-4939-0779-3_9-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
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Croxen MA, Law RJ, Scholz R, Keeney KM, Wlodarska M, Finlay BB. Recent advances in understanding enteric pathogenic Escherichia coli. Clin Microbiol Rev 2013; 26:822-80. [PMID: 24092857 PMCID: PMC3811233 DOI: 10.1128/cmr.00022-13] [Citation(s) in RCA: 899] [Impact Index Per Article: 74.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Although Escherichia coli can be an innocuous resident of the gastrointestinal tract, it also has the pathogenic capacity to cause significant diarrheal and extraintestinal diseases. Pathogenic variants of E. coli (pathovars or pathotypes) cause much morbidity and mortality worldwide. Consequently, pathogenic E. coli is widely studied in humans, animals, food, and the environment. While there are many common features that these pathotypes employ to colonize the intestinal mucosa and cause disease, the course, onset, and complications vary significantly. Outbreaks are common in developed and developing countries, and they sometimes have fatal consequences. Many of these pathotypes are a major public health concern as they have low infectious doses and are transmitted through ubiquitous mediums, including food and water. The seriousness of pathogenic E. coli is exemplified by dedicated national and international surveillance programs that monitor and track outbreaks; unfortunately, this surveillance is often lacking in developing countries. While not all pathotypes carry the same public health profile, they all carry an enormous potential to cause disease and continue to present challenges to human health. This comprehensive review highlights recent advances in our understanding of the intestinal pathotypes of E. coli.
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