Diagnostic Criteria in Peptic Ulcer Disease



The accurate detection of H. pylori, a major cause of peptic ulcer, is essential for managing infected patients. A number of invasive and noninvasive diagnostic methods are currently available. Tests differ in sensitivity and specificity, and the choice of which diagnostic method to use is highly personalized and influenced by clinical setting, cost, the pretest probability of infection, and the use of medications that generally reduce the density of bacteria and decrease the accuracy of test.

This chapter provides an overview of diagnostic tests used to identify H. pylori infection, depicts their general methodological aspects, and evaluates their validity and limitation in clinical practice.


Esophagogastroduodenoscopy Rapid urease test Urea breath test Stool antigen test 



Cytotoxin-associated gene A


Carbon dioxide




Enzyme immunoassay


Enzyme-linked immunosorbent assay


European Society for Pediatric Gastroenterology, Hepatology, and Nutrition


Fluorescence in situ hybridization


Food and Drug Administration


Fluorescence resonance energy transfer




Mucosa-associated lymphoid tissue


North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition


Polymerase chain reaction


Proton pump inhibitor


Rapid urease test


Stool antigen test


Urea breath test


Vacuolating cytotoxin A


Western blot



Supported by grant from the Medical University of Lodz (#502-03/1-156-04/502-14-343 to PM and #502-03/1-156-04/502-14-298 to MS), grant from National Science Centre (#UMO-2016/21/N/NZ5/01932 to PM and #UMO-2013/11/N/NZ7/02354 to MS), and Iuventus Plus program of the Polish Ministry of Science and Higher Education (IP2015 068774 to MS).


The authors have nothing to disclose.


  1. 1.
    Malfertheiner P, Megraud F, O’Morain CA, Atherton J, Axon ATR, Bazzoli F, et al. Management of Helicobacter pylori infection—the maastricht iv/ florence consensus report. Gut [Internet]. 2012 May [cited 2016 Nov 10];61(5):646–64. Available from:
  2. 2.
    Malfertheiner P, Megraud F, O’morain C, Bazzoli F, El-Omar E, Graham D, et al. Current concepts in the management of Helicobacter pylori infection: the maastricht III consensus report. Gut. 2007;56:772–81.CrossRefPubMedGoogle Scholar
  3. 3.
    Chey WD, Wong BCY. American college of gastroenterology guideline on the management of Helicobacter pylori Infection. Am J Gastroenterol. 2007;102:1808–25.CrossRefPubMedGoogle Scholar
  4. 4.
    Dore MP, Pes GM, Bassotti G, Usai-Satta P. Dyspepsia: when and how to test for Helicobacter pylori infection. Gastroenterol Res Pract. 2016;2016:1–9.CrossRefGoogle Scholar
  5. 5.
    Perna F, Ricci C, Gatta L, Bernabucci V, Cavina M, Miglioli M, et al. Diagnostic accuracy of a new rapid urease test (Pronto Dry), before and after treatment of Helicobacter pylori infection. Minerva Gastroenterol Dietol [Internet]. 2005 Sep [cited 2016 Nov 8];51(3):247–54. Available from:
  6. 6.
    Tian X-Y, Zhu H, Zhao J, She Q, Zhang G-X. Diagnostic performance of urea breath test, rapid urea test, and histology for Helicobacter pylori infection in patients with partial gastrectomy. J Clin Gastroenterol [Internet]. 2012 Apr [cited 2016 Nov 8];46(4):285–92. Available from:
  7. 7.
    Mégraud F, Lehours P. Helicobacter pylori detection and antimicrobial susceptibility testing. Clin Microbiol Rev. 2007;20(2):280–322.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Tzeng J, Lin Y, Chung S, Chu Y. Comparison of four diagnostic methods for Helicobacter pylori. 2005;17:339–343.Google Scholar
  9. 9.
    Rogge JD, Wagner DR, Carrico RJ, Glowinski EA, Mahoney SJ, Boguslaski RC, et al. Evaluation of a new urease reagent strip for detection of Helicobacter pylori in gastric biopsy specimens. Am J Gastroenterol [Internet]. 1995 Nov [cited 2016 Nov 8];90(11):1965–8. Available from:
  10. 10.
    Pylori H, Uotani T, Graham DY, DeBakey ME. Diagnosis of Helicobacter pylori using the rapid urease test. Ann Trans Med [Internet]. 2015 [cited 2016 Nov 7];3(1). Available from:
  11. 11.
    Tang J-H, Liu N-J, Cheng H-T, Lee C-S, Chu Y-Y, Sung K-F, et al. Endoscopic diagnosis of Helicobacter pylori infection by rapid urease test in bleeding peptic ulcers. J Clin Gastroenterol [Internet]. 2009 Feb [cited 2016 Nov 8];43(2):133–9. Available from:
  12. 12.
    Gisbert JP, Abraira V. Accuracy of Helicobacter pylori diagnostic tests in patients with bleeding peptic ulcer: a systematic review and meta-analysis. CME. Am J Gastroenterol [Internet]. 2006 Apr [cited 2016 Nov 9];101(4):848–63. Available from:
  13. 13.
    Fischbach W. Helicobacter pylori. Internist. 2009;50(8):979–87.CrossRefPubMedGoogle Scholar
  14. 14.
    Brandi G, Biavati B, Calabrese C, Granata M, Nannetti A, Mattarelli P, et al. Urease-positive bacteria other than Helicobacter pylori in human gastric juice and mucosa. Am J Gastroenterol [Internet]. 2006 Aug [cited 2016 Nov 8];101(8):1756–61. Available from:
  15. 15.
    Osaki T, Mabe K, Hanawa T, Kamiya S. Urease-positive bacteria in the stomach induce a false-positive reaction in a urea breath test for diagnosis of Helicobacter pylori infection. J Med Microbiol [Internet]. 2008 Jul 1 [cited 2016 Nov 8];57(7):814–9. Available from:
  16. 16.
    El-Zimaity H, Serra S, Szentgyorgyi E, Vajpeyi R, Samani A. Gastric biopsies: the gap between evidence-based medicine and daily practice in the management of gastric Helicobacter pylori infection. Can J Gastroenterol. 2013;27:e25–30.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Lee JY, Kim N. Diagnosis of Helicobacter pylori by invasive test: histology. Ann Trans Med [Internet]. AME Publications. 2015 Jan [cited 2016 Nov 13];3(1):10. Available from:
  18. 18.
    Miftahussurur M, Yamaoka Y. Diagnostic methods of Helicobacter pylori infection for epidemiological studies: critical importance of indirect test validation. BioMed Res Int. 2016;2016:1–14.CrossRefGoogle Scholar
  19. 19.
    Xuan S-H, Wu L-P, Zhou Y-G, Xiao M. Detection of clarithromycin-resistant Helicobacter pylori in clinical specimens by molecular methods: a review. J Glob Antimicrob Resist [Internet]. 2016 Mar [cited 2016 Nov 11];4:35–41. Available from:
  20. 20.
    Yilmaz Ö, Demiray E. Clinical role and importance of fluorescence in situ hybridization method in diagnosis of H. pylori infection and determination of clarithromycin resistance in H pylori eradication therapy. World J Gastroenterol [Internet]. 2007 [cited 2016 Nov 8];13(5):671–5. Available from:
  21. 21.
    Schmitt BH, Regner M, Mangold KA, Thomson RB, Kaul KL. PCR detection of clarithromycin-susceptible and -resistant Helicobacter pylori from formalin-fixed, paraffin-embedded gastric biopsies. Mod Pathol. 2013;26:1222–7.CrossRefPubMedGoogle Scholar
  22. 22.
    Mahachai V, Sirimontaporn N, Tumwasorn S, Thong-Ngam D, Vilaichone R-K. Sequential therapy in clarithromycin-sensitive and -resistant Helicobacter pylori based on polymerase chain reaction molecular test. J Gastroenterol Hepatol [Internet]. 2011 May [cited 2016 Nov 11];26(5):825–8. Available from:
  23. 23.
    Chung WC, Jeon EJ, Oh JH, Park JM, Kim TH, Cheung DY, et al. Dual-priming oligonucleotide-based multiplex PCR using tissue samples from the rapid urease test kit for the detection of Helicobacter pylori in bleeding peptic ulcers. Dig Liver Dis [Internet]. 2016 Aug [cited 2016 Nov 11];48(8):899–903. Available from:
  24. 24.
    Moosavian M, Tajbakhsh S, Samarbaf-Zadeh AR. Rapid detection of clarithromycin-resistant Helicobacter pylori in patients with dyspepsia by fluorescent in situ hybridization (FISH) compared with the E-test. Ann Saudi Med [Internet]. [cited 2016 Nov 11];27(2):84–8. Available from:
  25. 25.
    Monno R, Giorgio F, Carmine P, Soleo L, Cinquepalmi V, Ierardi E. Helicobacter pylori clarithromycin resistance detected by Etest and TaqMan real-time polymerase chain reaction: a comparative study. APMIS [Internet]. 2012 Sep [cited 2016 Nov 11];120(9):712–7. Available from:
  26. 26.
    Liu Q, Qi D, Kang J, Jin Y, Liu W, Gao W, et al. Efficacy of real-time PCR-based detection of Helicobacter pylori infection and genotypic resistance-guided quadruple therapy as the first-line treatment for functional dyspepsia with Helicobacter pylori infection. Eur J Gastroenterol Hepatol [Internet]. 2015 Mar [cited 2016 Nov 11];27(3):221–5. Available from:
  27. 27.
    Woo H-Y, Park D II, Park H, Kim M-K, Kim DH, Kim I-S, et al. Dual-priming oligonucleotide-based multiplex pcr for the detection of Helicobacter pylori and determination of clarithromycin resistance with gastric biopsy specimens. Helicobacter [Internet]. 2009 Feb [cited 2016 Nov 11];14(1):22–8. Available from:
  28. 28.
    Xiong Jing L, Tong Y, Wang Z, Mao M. Detection of clarithromycin-resistant Helicobacter pylori by stool pcr in children: a comprehensive review of literature. Helicobacter [Internet]. 2013 Apr [cited 2016 Nov 11];18(2):89–101. Available from:
  29. 29.
    Trebesius K, Panthel K, Strobel S, Vogt K, Faller G, Kirchner T, et al. Rapid and specific detection of Helicobacter pylori macrolide resistance in gastric tissue by fluorescent in situ hybridisation. Gut [Internet]. 2000;46(5):608–14. Available from: CrossRefGoogle Scholar
  30. 30.
    Choi YS, Kim YC, Baek KJ, Choi Y. In situ detection of bacteria within paraffin-embedded tissues using a digoxin-labeled DNA probe targeting 16S rRNA. J Vis Exp [Internet]. 2015 May 21 [cited 2016 Nov 11];(99). Available from:
  31. 31.
    Suzuki T, Matsuo K, Sawaki A, Ito H, Hirose K, Wakai K, et al. Systematic review and meta-analysis: importance of CagA status for successful eradication of Helicobacter pylori infection. Aliment Pharmacol Ther. 2006;24(2):273–80.CrossRefPubMedGoogle Scholar
  32. 32.
    Fry LC, Curioso WH, Rickes S, Horton G, Hirschowitz BI, Monkemuller K. Comparison of 13C- urea blood test to 13C-breath test and rapid urease test for the diagnosis of Helicobacter pylori infection. Acta Gastroenterol Latinoam [Internet]. 2005;35(4):225–9. Available from: PubMedGoogle Scholar
  33. 33.
    Kazemi S, Tavakkoli H, Habizadeh MR, Emami MH. Diagnostic values of Helicobacter pylori diagnostic tests: Stool antigen test, urea breath test, rapid urease test, serology and histology. J Res Med Sci. 2011;16(9):1097–104.PubMedPubMedCentralGoogle Scholar
  34. 34.
    Ferwana M, Abdulmajeed I, Alhajiahmed A, Madani W, Firwana B, Hasan R, et al. Accuracy of urea breath test in Helicobacter pylori infection: meta-analysis. World J Gastroenterol [Internet]. Baishideng Publishing Group Inc. 2015 Jan 28 [cited 2016 Nov 7];21(4):1305–14. Available from:
  35. 35.
    Rapid T, Service R. Stool Antigen Tests for Helicobacter pylori Infection: A Review of Clinical and Cost-Effectiveness and Guidelines. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2015;08:1–41. CADTH Rapid Response Reports.Google Scholar
  36. 36.
    Asaka M, Kato M, Takahashi S, Fukuda Y, Sugiyama T, Ota H, et al. Guidelines for the management of Helicobacter pylori infection in japan: 2009 revised edition. Helicobacter [Internet]. 2010 Feb [cited 2016 Nov 10];15(1):1–20. Available from:
  37. 37.
    Koletzko S, Jones NL, Goodman KJ, Gold B, Rowland M, Cadranel S, et al. Evidence-based guidelines from ESPGHAN and NASPGHAN for Helicobacter pylori infection in children. J Pediatr Gastroenterol Nutr [Internet]. 2011 May [cited 2016 Nov 9];1. Available from:
  38. 38.
    Yang HR, Seo JK. Diagnostic accuracy of the 13C-urea breath test in children: Adjustment of the cut-off value according to age. J Gastroenterol Hepatol [Internet]. 2005 Feb [cited 2016 Nov 9];20(2):264–9. Available from:
  39. 39.
    Machado RS, Patrício FRS, Kawakami E. 13C-urea breath test to diagnose Helicobacter pylori infection in children aged up to 6 years. Helicobacter [Internet]. 2004 Feb [cited 2016 Nov 9];9(1):39–45. Available from:
  40. 40.
    Guarner J, Kalach N, Elitsur Y, Koletzko S. Helicobacter pylori diagnostic tests in children: review of the literature from 1999 to 2009. Eur J Pediatr [Internet]. 2010 Jan 18 [cited 2016 Nov 9];169(1):15–25. Available from:

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.Department of BiochemistryFaculty of Medicine, Medical University of LodzLodzPoland

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