Review Article| Volume 35, ISSUE 2, P333-344, June 2015

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Markers of Intestinal Inflammation for the Diagnosis of Infectious Gastroenteritis

  • Author Footnotes
    1 These authors contributed equally to this work.
    Mark D. Gonzalez
    1 These authors contributed equally to this work.
    Division of Laboratory and Genomic Medicine, Department of Pathology and Immunology, Washington University School of Medicine, Washington University in St. Louis, 660 South Euclid Avenue, St Louis, MO 63110, USA
    Search for articles by this author
  • Author Footnotes
    1 These authors contributed equally to this work.
    Craig B. Wilen
    1 These authors contributed equally to this work.
    Department of Pathology and Immunology, Washington University School of Medicine, Washington University in St. Louis, 660 South Euclid Avenue, St. Louis, MO 63110, USA
    Search for articles by this author
  • Carey-Ann D. Burnham
    Corresponding author. Washington University School of Medicine, Washington University in St. Louis, 660 South Euclid Avenue, Campus Box 8118, St. Louis, MO 63110.
    Department of Pathology and Immunology, Washington University School of Medicine, Washington University in St. Louis, 660 South Euclid Avenue, St. Louis, MO 63110, USA
    Search for articles by this author
  • Author Footnotes
    1 These authors contributed equally to this work.
Published:March 19, 2015DOI:


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        • Liu L.
        • Johnson H.L.
        • Cousens S.
        • et al.
        Global, regional, and national causes of child mortality: an updated systematic analysis for 2010 with time trends since 2000.
        Lancet. 2012; 379: 2151-2161
        • Scallan E.
        • Griffin P.M.
        • Angulo F.J.
        • et al.
        Foodborne illness acquired in the United States–unspecified agents.
        Emerg Infect Dis. 2011; 17: 16-22
        • Perry M.D.
        • Corden S.A.
        • Howe R.A.
        Evaluation of the Luminex xTAG Gastrointestinal Pathogen Panel and the Savyon Diagnostics Gastrointestinal Infection Panel for the detection of enteric pathogens in clinical samples.
        J Med Microbiol. 2014; 63: 1419-1426
        • Khare R.
        • Espy M.J.
        • Cebelinski E.
        • et al.
        Comparative evaluation of two commercial multiplex panels for detection of gastrointestinal pathogens by use of clinical stool specimens.
        J Clin Microbiol. 2014; 52: 3667-3673
        • Halligan E.
        • Edgeworth J.
        • Bisnauthsing K.
        • et al.
        Multiplex molecular testing for management of infectious gastroenteritis in a hospital setting: a comparative diagnostic and clinical utility study.
        Clin Microbiol Infect. 2014; 20: O460-O467
        • Wessels E.
        • Rusman L.G.
        • van Bussel M.J.
        • et al.
        Added value of multiplex Luminex Gastrointestinal Pathogen Panel (xTAG® GPP) testing in the diagnosis of infectious gastroenteritis.
        Clin Microbiol Infect. 2014; 20: O182-O187
        • Claas E.C.
        • Burnham C.A.
        • Mazzulli T.
        • et al.
        Performance of the xTAG® gastrointestinal pathogen panel, a multiplex molecular assay for simultaneous detection of bacterial, viral, and parasitic causes of infectious gastroenteritis.
        J Microbiol Biotechnol. 2013; 23: 1041-1045
        • Gabay C.
        • Kushner I.
        Acute-phase proteins and other systemic responses to inflammation.
        N Engl J Med. 1999; 340: 448-454
        • Abernethy T.J.
        • Avery O.T.
        The occurrence during acute infections of a protein not normally present in the blood: I. Distribution of the reactive protein in patients' sera and the effect of calcium on the flocculation reaction with C polysaccharide of pneumococcus.
        J Exp Med. 1941; 73: 173-182
        • Borgnolo G.
        • Barbone F.
        • Guidobaldi G.
        • et al.
        C-reactive protein in viral and bacterial gastroenteritis in childhood.
        Acta Paediatr. 1996; 85: 670-674
        • Elsing C.
        • Ernst S.
        • Kayali N.
        • et al.
        Lipopolysaccharide binding protein, interleukin-6 and C-reactive protein in acute gastrointestinal infections: value as biomarkers to reduce unnecessary antibiotic therapy.
        Infection. 2011; 39: 327-331
        • Hsu T.R.
        • Chen S.J.
        • Wu T.C.
        • et al.
        Tumor necrosis factor-alpha and interleukin-10 in viral and bacterial gastroenteritis in children.
        J Chin Med Assoc. 2005; 68: 250-253
        • Lin C.H.
        • Hsieh C.C.
        • Chen S.J.
        • et al.
        The diagnostic value of serum interleukins 6 and 8 in children with acute gastroenteritis.
        J Pediatr Gastroenterol Nutr. 2006; 43: 25-29
        • Meloni G.F.
        • Tomasi P.A.
        • Spanu P.
        • et al.
        C-reactive protein levels for diagnosis of Salmonella gastroenteritis.
        Pediatr Infect Dis J. 1999; 18: 471-473
        • Sýkora J.
        • Siala K.
        • Huml M.
        • et al.
        Evaluation of faecal calprotectin as a valuable non-invasive marker in distinguishing gut pathogens in young children with acute gastroenteritis.
        Acta Paediatr. 2010; 99: 1389-1395
        • Weh J.
        • Antoni C.
        • Weiß C.
        • et al.
        Discriminatory potential of C-reactive protein, cytokines, and fecal markers in infectious gastroenteritis in adults.
        Diagn Microbiol Infect Dis. 2013; 77: 79-84
        • Mangiarotti P.
        • Moulin F.
        • Palmer P.
        • et al.
        Interferon-alpha in viral and bacterial gastroenteritis: a comparison with C-reactive protein and interleukin-6.
        Acta Paediatr. 1999; 88: 592-594
        • Yeung C.Y.
        • Lee H.C.
        • Lin S.P.
        • et al.
        Serum cytokines in differentiating between viral and bacterial enterocolitis.
        Ann Trop Paediatr. 2004; 24: 337-343
        • Kim D.H.
        • Kang S.H.
        • Jeong W.S.
        • et al.
        Serum C-reactive protein (CRP) levels in young adults can be used to discriminate between inflammatory and non-inflammatory diarrhea.
        Dig Dis Sci. 2013; 58: 504-508
        • Grzybowski A.
        • Sak J.
        Edmund Biernacki (1866–1911): discoverer of the erythrocyte sedimentation rate. On the 100th anniversary of his death.
        Clin Dermatol. 2011; 29: 697-703
        • Chen S.M.
        • Ku M.S.
        • Lee M.Y.
        • et al.
        Diagnostic performance of serum interleukin-6 and interleukin-10 levels and clinical predictors in children with rotavirus and norovirus gastroenteritis.
        Cytokine. 2012; 59: 299-304
        • Riedel S.
        • Carroll K.C.
        Laboratory detection of sepsis: biomarkers and molecular approaches.
        Clin Lab Med. 2013; 33: 413-437
        • Tanaka T.
        • Narazaki M.
        • Kishimoto T.
        IL-6 in inflammation, immunity, and disease.
        Cold Spring Harb Perspect Biol. 2014; 6: a016295
        • Popa C.
        • Netea M.G.
        • van Riel P.L.
        • et al.
        The role of TNF-alpha in chronic inflammatory conditions, intermediary metabolism, and cardiovascular risk.
        J Lipid Res. 2007; 48: 751-762
        • Stathaki M.I.
        • Koukouraki S.I.
        • Karkavitsas N.S.
        • et al.
        Role of scintigraphy in inflammatory bowel disease.
        World J Gastroenterol. 2009; 15: 2693-2700
        • Harris J.C.
        • Dupont H.L.
        • Hornick R.B.
        Fecal leukocytes in diarrheal illness.
        Ann Intern Med. 1972; 76: 697-703
        • Alasmari F.
        • Seiler S.M.
        • Hink T.
        • et al.
        Prevalence and risk factors for asymptomatic Clostridium difficile carriage.
        Clin Infect Dis. 2014; 59: 216-222
        • Burnham C.A.
        • Carroll K.C.
        Diagnosis of Clostridium difficile infection: an ongoing conundrum for clinicians and for clinical laboratories.
        Clin Microbiol Rev. 2013; 26: 604-630
        • Dubberke E.R.
        • Han Z.
        • Bobo L.
        • et al.
        Impact of clinical symptoms on interpretation of diagnostic assays for Clostridium difficile infections.
        J Clin Microbiol. 2011; 49: 2887-2893
        • Savola K.L.
        • Baron E.J.
        • Tompkins L.S.
        • et al.
        Fecal leukocyte stain has diagnostic value for outpatients but not inpatients.
        J Clin Microbiol. 2001; 39: 266-269
        • Däbritz J.
        • Musci J.
        • Foell D.
        Diagnostic utility of faecal biomarkers in patients with irritable bowel syndrome.
        World J Gastroenterol. 2014; 20: 363-375
        • Guerrant R.L.
        • Araujo V.
        • Soares E.
        • et al.
        Measurement of fecal lactoferrin as a marker of fecal leukocytes.
        J Clin Microbiol. 1992; 30: 1238-1242
        • Naidu A.S.
        • Arnold R.R.
        Influence of lactoferrin on host-microbe interactions.
        in: Lactoferrin–-interactions and biological functions. vol. 28. Humana Press, Totowa (NJ)1997: 259-275
        • Uchida K.
        • Matsuse R.
        • Tomita S.
        • et al.
        Immunochemical detection of human lactoferrin in feces as a new marker for inflammatory gastrointestinal disorders and colon cancer.
        Clin Biochem. 1994; 27: 259-264
        • Burri E.
        • Beglinger C.
        The use of fecal calprotectin as a biomarker in gastrointestinal disease.
        Expert Rev Gastroenterol Hepatol. 2014; 8: 197-210
        • Gill C.J.
        • Lau J.
        • Gorbach S.L.
        • et al.
        Diagnostic accuracy of stool assays for inflammatory bacterial gastroenteritis in developed and resource-poor countries.
        Clin Infect Dis. 2003; 37: 365-375
        • Greenwald B.
        From guaiac to immune fecal occult blood tests: the emergence of technology in colorectal cancer screening.
        Gastroenterol Nurs. 2005; 28: 90-96
        • Røseth A.G.
        • Schmidt P.N.
        • Fagerhol M.K.
        Correlation between faecal excretion of indium-111-labelled granulocytes and calprotectin, a granulocyte marker protein, in patients with inflammatory bowel disease.
        Scand J Gastroenterol. 1999; 34: 50-54
        • Dolwani S.
        • Metzner M.
        • Wassell J.J.
        • et al.
        Diagnostic accuracy of faecal calprotectin estimation in prediction of abnormal small bowel radiology.
        Aliment Pharmacol Ther. 2004; 20: 615-621
        • Savino F.
        • Castagno E.
        • Calabrese R.
        • et al.
        High faecal calprotectin levels in healthy, exclusively breast-fed infants.
        Neonatology. 2010; 97: 299-304
        • Campeotto F.
        • Butel M.J.
        • Kalach N.
        • et al.
        High faecal calprotectin concentrations in newborn infants.
        Arch Dis Child Fetal Neonatal Ed. 2004; 89: F353-F355
        • Olafsdottir E.
        • Aksnes L.
        • Fluge G.
        • et al.
        Faecal calprotectin levels in infants with infantile colic, healthy infants, children with inflammatory bowel disease, children with recurrent abdominal pain and healthy children.
        Acta Paediatr. 2002; 91: 45-50
        • Hestvik E.
        • Tumwine J.K.
        • Tylleskar T.
        • et al.
        Faecal calprotectin concentrations in apparently healthy children aged 0–12 years in urban Kampala, Uganda: a community-based survey.
        BMC Pediatr. 2011; 11: 9
        • Husebye E.
        • Tøn H.
        • Johne B.
        Biological variability of fecal calprotectin in patients referred for colonoscopy without colonic inflammation or neoplasm.
        Am J Gastroenterol. 2001; 96: 2683-2687
        • Naismith G.D.
        • Smith L.A.
        • Barry S.J.
        • et al.
        A prospective single-centre evaluation of the intra-individual variability of faecal calprotectin in quiescent Crohn's disease.
        Aliment Pharmacol Ther. 2013; 37: 613-621
        • Sherwood R.A.
        Faecal markers of gastrointestinal inflammation.
        J Clin Pathol. 2012; 65: 981-985
        • Shastri Y.M.
        • Bergis D.
        • Povse N.
        • et al.
        Prospective multicenter study evaluating fecal calprotectin in adult acute bacterial diarrhea.
        Am J Med. 2008; 121: 1099-1106
        • Nielsen H.L.
        • Engberg J.
        • Ejlertsen T.
        • et al.
        Evaluation of fecal calprotectin in Campylobacter concisus and Campylobacter jejuni/coli gastroenteritis.
        Scand J Gastroenterol. 2013; 48: 633-635
        • Chen C.C.
        • Huang J.L.
        • Chang C.J.
        • et al.
        Fecal calprotectin as a correlative marker in clinical severity of infectious diarrhea and usefulness in evaluating bacterial or viral pathogens in children.
        J Pediatr Gastroenterol Nutr. 2012; 55: 541-547