Korean J Gastroenterol.  2018 Nov;72(5):229-236. 10.4166/kjg.2018.72.5.229.

Diagnosis of Helicobacter pylori Infection

• Huh CW
• Kim BW

• KMID: 2426863
• DOI: http://doi.org/10.4166/kjg.2018.72.5.229

Abstract

Accurate diagnosis of Helicobacter pylori (H. pylori) infection is mandatory for the effective management of many gastroduodenal diseases. Currently, various diagnostic methods are available for detecting these infections, and the choice of method should take into account the clinical condition, accessibility, advantage, disadvantage, as well as cost-effectiveness. The diagnostic methods are divided into invasive (endoscopic-based) and non-invasive methods. Non-invasive methods included urea breath test, stool antigen test, serology, and molecular methods. Invasive methods included endoscopic imaging, rapid urease test, histology, culture, and molecular methods. In this article, we provide a review of the currently available options and recent advances of various diagnostic methods.

Keyword

Helicobacter pylori; Diagnosis; Guideline

MeSH Terms

Breath Tests
Diagnosis*
Helicobacter pylori*
Helicobacter*
Methods
Urea
Urease
Urea
Urease

Figure

• 

  Fig. 1 Rapid urase test. When Helicobacter pylori produce ammonia then pH will increase and the color of the medium will change from yellow to red.

• 

  Fig. 2 Giemsa stain. The Helicobacter pylori organisms (arrows) are present in Giemsa stain (×400).

Reference

1. Malfertheiner P, Megraud F, O'Morain CA, et al. Management of Helicobacter pylori infection-the Maastricht V/Florence consensus report. Gut. 2017; 66:6–30.

2. Wang YK, Kuo FC, Liu CJ, et al. Diagnosis of Helicobacter pylori infection: current options and developments. World J Gastroenterol. 2015; 21:11221–11235.

3. Lopes AI, Vale FF, Oleastro M. Helicobacter pylori infection - recent developments in diagnosis. World J Gastroenterol. 2014; 20:9299–9313.

4. Gisbert JP, Calvet X. Helicobacter pylori “test-and-treat” strategy for management of dyspepsia: a comprehensive review. Clin Transl Gastroenterol. 2013; 4:e32.

5. Nocon M, Kuhlmann A, Leodolter A, et al. Efficacy and cost-effectiveness of the 13C-urea breath test as the primary diagnostic investigation for the detection of Helicobacter pylori infection compared to invasive and non-invasive diagnostic tests. GMS Health Technol Assess. 2009; 5:Doc14.

6. Gisbert JP, Pajares JM. Review article: 13C-urea breath test in the diagnosis of Helicobacter pylori infection -- a critical review. Aliment Pharmacol Ther. 2004; 20:1001–1017.

7. 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. 2010; 169:15–25.

8. Machado RS, Patrício FR, Kawakami E. 13C-urea breath test to diagnose Helicobacter pylori infection in children aged up to 6 years. Helicobacter. 2004; 9:39–45.

9. McColl KE. Clinical practice. Helicobacter pylori infection. N Engl J Med. 2010; 362:1597–1604.

10. Zhou X, Su J, Xu G, Zhang G. Accuracy of stool antigen test for the diagnosis of Helicobacter pylori infection in children: a metaanalysis. Clin Res Hepatol Gastroenterol. 2014; 38:629–638.

11. Gisbert JP, de la Morena F, Abraira V. Accuracy of monoclonal stool antigen test for the diagnosis of H. pylori infection: a systematic review and meta-analysis. Am J Gastroenterol. 2006; 101:1921–1930.

12. Leodolter A, Domínguez-Muñoz JE, von Arnim U, Kahl S, Peitz U, Malfertheiner P. Validity of a modified 13C-urea breath test for pre- and posttreatment diagnosis of Helicobacter pylori infection in the routine clinical setting. Am J Gastroenterol. 1999; 94:2100–2104.

13. Korkmaz H, Kesli R, Karabagli P, Terzi Y. Comparison of the diagnostic accuracy of five different stool antigen tests for the diagnosis of Helicobacter pylori infection. Helicobacter. 2013; 18:384–391.

14. Kesli R, Gokturk HS, Erbayrak M, Karabagli P, Terzi Y. Comparison of the diagnostic values of the 3 different stool antigen tests for the noninvasive diagnosis of Helicobacter pylori infection. J Investig Med. 2010; 58:982–986.

15. Shimoyama T. Stool antigen tests for the management of Helicobacter pylori infection. World J Gastroenterol. 2013; 19:8188–8191.

16. Burucoa C, Delchier JC, Courillon-Mallet A, et al. Comparative evaluation of 29 commercial Helicobacter pylori serological kits. Helicobacter. 2013; 18:169–179.

17. Pan KF, Formichella L, Zhang L, et al. Helicobacter pylori antibody responses and evolution of precancerous gastric lesions in a Chinese population. Int J Cancer. 2014; 134:2118–2125.

18. Khalifeh Gholi M, Kalali B, Formichella L, et al. Helicobacter pylori FliD protein is a highly sensitive and specific marker for serologic diagnosis of H. pylori infection. Int J Med Microbiol. 2013; 303:618–623.

19. Formichella L, Romberg L, Bolz C, et al. A novel line immunoassay based on recombinant virulence factors enables highly specific and sensitive serologic diagnosis of Helicobacter pylori infection. Clin Vaccine Immunol. 2013; 20:1703–1710.

20. Ho B, Marshall BJ. Accurate diagnosis of Helicobacter pylori. Serologic testing. Gastroenterol Clin North Am. 2000; 29:853–862.

21. Yamada K, Sugiyama T, Mihara H, et al. Fragmented CagA protein is highly immunoreactive in Japanese patients. Helicobacter. 2012; 17:187–192.

22. Leodolter A, Vaira D, Bazzoli F, et al. European multicentre validation trial of two new non-invasive tests for the detection of Helicobacter pylori antibodies: urine-based ELISA and rapid urine test. Aliment Pharmacol Ther. 2003; 18:927–931.

23. Giorgio F, Ierardi E, Sorrentino C, et al. Helicobacter pylori DNA isolation in the stool: an essential pre-requisite for bacterial noninvasive molecular analysis. Scand J Gastroenterol. 2016; 51:1429–1432.

24. George S, Mamani N, Lucero Y, et al. Detection of Helicobacter pylori by real-time PCR for 16s rRNA in stools of noninfected healthy children, using ELISA antigen stool test as the gold standard. Helicobacter. 2016; 21:606–612.

25. Wongphutorn P, Chomvarin C, Sripa B, Namwat W, Faksri K. Detection and genotyping of Helicobacter pylori in saliva versus stool samples from asymptomatic individuals in Northeastern Thailand reveals intra-host tissue-specific H. pylori subtypes. BMC Microbiol. 2018; 18:10.

26. Chaudhry S, Idrees M, Izhar M, Butt AK, Khan AA. Simultaneous amplification of two bacterial genes: more reliable method of Helicobacter pylori detection in microbial rich dental plaque samples. Curr Microbiol. 2011; 62:78–83.

27. Kabir S. Detection of Helicobacter pylori DNA in feces and saliva by polymerase chain reaction: a review. Helicobacter. 2004; 9:115–123.

28. Adamsson I, Edlund C, Nord CE. Microbial ecology and treatment of Helicobacter pylori infections: review. J Chemother. 2000; 12:5–16.

29. Shimoyama T, Sawada Y, Sawada N, Chinda D, Fukuda S. Accuracy of a stick-type kit and enzyme-linked immunosorbent assay in detecting Helicobacter pylori antibodies in urine of people living in the Japan sea region of northern Japan. Jpn J Infect Dis. 2017; 70:207–209.

30. Mabe K, Kikuchi S, Okuda M, Takamasa M, Kato M, Asaka M. Diagnostic accuracy of urine Helicobacter pylori antibody test in junior and senior high school students in Japan. Helicobacter. 2017; 22:e12329.

31. El Khadir M, Alaoui Boukhris S, Benajah DA, et al. Detection of Helicobacter pylori urease antigen in saliva in patients with different gastric H. pylori status. J Chin Med Assoc. 2016; 79:363–367.

33. Anand PS, Kamath KP, Anil S. Role of dental plaque, saliva and periodontal disease in Helicobacter pylori infection. World J Gastroenterol. 2014; 20:5639–5653.

34. Kato T, Yagi N, Kamada T, et al. Diagnosis of Helicobacter pylori infection in gastric mucosa by endoscopic features: a multicenter prospective study. Dig Endosc. 2013; 25:508–518.

35. Yagi K, Nakamura A, Sekine A. Characteristic endoscopic and magnified endoscopic findings in the normal stomach without Helicobacter pylori infection. J Gastroenterol Hepatol. 2002; 17:39–45.

36. Qi Q, Guo C, Ji R, Li Z, Zuo X, Li Y. Diagnostic performance of magnifying endoscopy for Helicobacter pylori infection: a meta-analysis. PLoS One. 2016; 11:e0168201.

37. Dohi O, Yagi N, Onozawa Y, et al. Linked color imaging improves endoscopic diagnosis of active Helicobacter pylori infection. Endosc Int Open. 2016; 4:E800–E805.

38. Ji R, Li YQ, Gu XM, Yu T, Zuo XL, Zhou CJ. Confocal laser endomicroscopy for diagnosis of Helicobacter pylori infection: a prospective study. J Gastroenterol Hepatol. 2010; 25:700–705.

39. Woo JS, el-Zimaity HM, Genta RM, Yousfi MM, Graham DY. The best gastric site for obtaining a positive rapid ureas test. Helicobacter. 1996; 1:256–259.

40. el-Zimaity HM, al-Assi MT, Genta RM, Graham DY. Confirmation of successful therapy of Helicobacter pylori infection: number and site of biopsies or a rapid urease test. Am J Gastroenterol. 1995; 90:1962–1964.

41. Vaira D, Vakil N, Gatta L, et al. Accuracy of a new ultrafast rapid urease test to diagnose Helicobacter pylori infection in 1000 consecutive dyspeptic patients. Aliment Pharmacol Ther. 2010; 31:331–338.

42. Kim SG, Jung HK, Lee HL, et al. Guidelines for the diagnosis and treatment of Helicobacter pylori infection in Korea, 2013 revised edition. J Gastroenterol Hepatol. 2014; 29:1371–1386.

43. Moon SW, Kim TH, Kim HS, et al. United rapid urease test is superior than separate test in detecting Helicobacter pylori at the gastric antrum and body specimens. Clin Endosc. 2012; 45:392–396.

44. Lan HC, Chen TS, Li AF, Chang FY, Lin HC. Additional corpus biopsy enhances the detection of Helicobacter pylori infection in a background of gastritis with atrophy. BMC Gastroenterol. 2012; 12:182.

45. Attumi TA, Graham DY. Follow-up testing after treatment of Helicobacter pylori infections: cautions, caveats, and recommendations. Clin Gastroenterol Hepatol. 2011; 9:373–375.

46. Ozaslan E, Koseoglu T, Purnak T, Yildiz A. A forgotten cause of false negative rapid urease test: formalin contamination of the sample. Hepatogastroenterology. 2010; 57:2. preceding table of contents.

47. Braden B. Diagnosis of Helicobacter pylori infection. BMJ. 2012; 344:e828.

48. Hartman DJ, Owens SR. Are routine ancillary stains required to diagnose Helicobacter infection in gastric biopsy specimens? An institutional quality assurance review. Am J Clin Pathol. 2012; 137:255–260.

49. Wang XI, Zhang S, Abreo F, Thomas J. The role of routine immunohistochemistry for Helicobacter pylori in gastric biopsy. Ann Diagn Pathol. 2010; 14:256–259.

50. Doglioni C, Turrin M, Macrì E, Chiarelli C, Germanà B, Barbareschi M. HpSS: a new silver staining method for Helicobacter pylori. J Clin Pathol. 1997; 50:461–464.

51. El-Zimaity HM, Segura AM, Genta RM, Graham DY. Histologic assessment of Helicobacter pylori status after therapy: comparison of Giemsa, Diff-Quik, and Genta stains. Mod Pathol. 1998; 11:288–291.

52. Toulaymat M, Marconi S, Garb J, Otis C, Nash S. Endoscopic biopsy pathology of Helicobacter pylori gastritis. Comparison of bacterial detection by immunohistochemistry and Genta stain. Arch Pathol Lab Med. 1999; 123:778–781.

53. Satoh K, Kimura K, Taniguchi Y, et al. Biopsy sites suitable for the diagnosis of Helicobacter pylori infection and the assessment of the extent of atrophic gastritis. Am J Gastroenterol. 1998; 93:569–573.

54. Lee JH, Park YS, Choi KS, et al. Optimal biopsy site for Helicobacter pylori detection during endoscopic mucosectomy in patients with extensive gastric atrophy. Helicobacter. 2012; 17:405–410.

55. Khulusi S, Mendall MA, Patel P, Levy J, Badve S, Northfield TC. Helicobacter pylori infection density and gastric inflammation in duodenal ulcer and non-ulcer subjects. Gut. 1995; 37:319–324.

56. Bayerdörffer E, Lehn N, Hatz R, et al. Difference in expression of Helicobacter pylori gastritis in antrum and body. Gastroenterology. 1992; 102:1575–1582.

57. Mégraud F, Lehours P. Helicobacter pylori detection and antimicrobial susceptibility testing. Clin Microbiol Rev. 2007; 20:280–322.

58. LeszczyXMLLink_XYZska K, Namiot A, Namiot Z, et al. Patient factors affecting culture of Helicobacter pylori isolated from gastric mucosal specimens. Adv Med Sci. 2010; 55:161–166.

59. Choi KD, Kim N, Lee DH, et al. Analysis of the 3′ variable region of the cagA gene of Helicobacter pylori isolated in Koreans. Dig Dis Sci. 2007; 52:960–966.

60. Kim JM, Kim JS, Jung HC, Kim N, Kim YJ, Song IS. Distribution of antibiotic MICs for Helicobacter pylori strains over a 16-year period in patients from Seoul, South Korea. Antimicrob Agents Chemother. 2004; 48:4843–4847.

61. Lehours P, Siffré E, Mégraud F. DPO multiplex PCR as an alternative to culture and susceptibility testing to detect Helicobacter pylori and its resistance to clarithromycin. BMC Gastroenterol. 2011; 11:112.

62. Woo HY, Park DI, Park H, et al. Dual-priming oligonucleotide-based multiplex PCR for the detection of Helicobacter pylori and determination of clarithromycin resistance with gastric biopsy specimens. Helicobacter. 2009; 14:22–28.

63. Cerqueira L, Fernandes RM, Ferreira RM, et al. Validation of a fluorescence in situ hybridization method using peptide nucleic acid probes for detection of Helicobacter pylori clarithromycin resistance in gastric biopsy specimens. J Clin Microbiol. 2013; 51:1887–1893.

64. Gisbert JP, Abraira V. Accuracy of Helicobacter pylori diagnostic tests in patients with bleeding peptic ulcer: a systematic review and meta-analysis. Am J Gastroenterol. 2006; 101:848–863.

65. Choi YJ, Kim N, Lim J, et al. Accuracy of diagnostic tests for Helicobacter pylori in patients with peptic ulcer bleeding. Helicobacter. 2012; 17:77–85.

66. Ramírez-Lázaro MJ, Lario S, Casalots A, et al. Real-time PCR improves Helicobacter pylori detection in patients with peptic ulcer bleeding. PLoS One. 2011; 6:e20009.

67. Chey WD, Wong BC, Practice Parameters. American college of gastroenterology guideline on the management of Helicobacter pylori infection. Am J Gastroenterol. 2007; 102:1808–1825.

68. Tian XY, Zhu H, Zhao J, She Q, Zhang GX. Diagnostic performance of urea breath test, rapid urea test, and histology for Helicobacter pylori infection in patients with partial gastrectomy: a metaanalysis. J Clin Gastroenterol. 2012; 46:285–292.

69. Lee SY. New guidelines for Helicobacter pylori treatment: comparisons between Korea and Japan. Korean J Gastroenterol. 2014; 63:151–157.