Skip to main content
Gut logoLink to Gut
. 2000 Mar;46(3):321–326. doi: 10.1136/gut.46.3.321

Importance of Helicobacter pylori cagA and vacA status for the efficacy of antibiotic treatment

L-J van Doorn 1, P Schneeberger 1, N Nouhan 1, A Plaisier 1, W Quint 1, W A de Boer 1
PMCID: PMC1727836  PMID: 10673291

Abstract

BACKGROUND—Virulence factors of Helicobacter pylori are associated with peptic ulcer disease and may be also associated with the efficacy of treatment.
AIMS—To determine the relation between the vacA and the cagA status of H pylori, clinical disease, and treatment outcome.
PATIENTS—121 patients with H pylori infection and peptic ulcer disease or functional dyspepsia were treated by quadruple antibiotic therapy in two groups for one and two days, respectively.
METHODS—DNA was isolated from gastric antral biopsy specimens, taken before and after treatment, and the vacA and cagA status was determined by polymerase chain reaction and reverse hybridisation.
RESULTS—Peptic ulcer disease was significantly associated with the vacA s1 type, and cagA positivity, but not with the vacA m type. Treatment efficacy was significantly higher in patients with peptic ulcer disease, or infected with cagA+/vacA s1 strains.
CONCLUSIONS—The strong association between the cagA and vacA status and peptic ulcer disease was confirmed. Cure rates seem to be higher for patients with cagA+/vacA s1 H pylori strains, which is consistent with the higher cure rate observed among ulcer patients compared with functional dyspepsia patients. Therefore, treatment studies may require stratification for presence of ulcers as well as H pylori genotypes.


Keywords: Helicobacter pylori; virulence; treatment; vacA; cagA

Full Text

The Full Text of this article is available as a PDF (140.8 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Atherton J. C., Cao P., Peek R. M., Jr, Tummuru M. K., Blaser M. J., Cover T. L. Mosaicism in vacuolating cytotoxin alleles of Helicobacter pylori. Association of specific vacA types with cytotoxin production and peptic ulceration. J Biol Chem. 1995 Jul 28;270(30):17771–17777. doi: 10.1074/jbc.270.30.17771. [DOI] [PubMed] [Google Scholar]
  2. Atherton J. C., Peek R. M., Jr, Tham K. T., Cover T. L., Blaser M. J. Clinical and pathological importance of heterogeneity in vacA, the vacuolating cytotoxin gene of Helicobacter pylori. Gastroenterology. 1997 Jan;112(1):92–99. doi: 10.1016/s0016-5085(97)70223-3. [DOI] [PubMed] [Google Scholar]
  3. Atherton J. C. The clinical relevance of strain types of Helicobacter pylori. Gut. 1997 Jun;40(6):701–703. doi: 10.1136/gut.40.6.701. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Beales I. L., Crabtree J. E., Scunes D., Covacci A., Calam J. Antibodies to CagA protein are associated with gastric atrophy in Helicobacter pylori infection. Eur J Gastroenterol Hepatol. 1996 Jul;8(7):645–649. [PubMed] [Google Scholar]
  5. Blaser M. J. Intrastrain differences in Helicobacter pylori: a key question in mucosal damage? Ann Med. 1995 Oct;27(5):559–563. doi: 10.3109/07853899509002469. [DOI] [PubMed] [Google Scholar]
  6. Boom R., Sol C. J., Salimans M. M., Jansen C. L., Wertheim-van Dillen P. M., van der Noordaa J. Rapid and simple method for purification of nucleic acids. J Clin Microbiol. 1990 Mar;28(3):495–503. doi: 10.1128/jcm.28.3.495-503.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Censini S., Lange C., Xiang Z., Crabtree J. E., Ghiara P., Borodovsky M., Rappuoli R., Covacci A. cag, a pathogenicity island of Helicobacter pylori, encodes type I-specific and disease-associated virulence factors. Proc Natl Acad Sci U S A. 1996 Dec 10;93(25):14648–14653. doi: 10.1073/pnas.93.25.14648. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Covacci A., Censini S., Bugnoli M., Petracca R., Burroni D., Macchia G., Massone A., Papini E., Xiang Z., Figura N. Molecular characterization of the 128-kDa immunodominant antigen of Helicobacter pylori associated with cytotoxicity and duodenal ulcer. Proc Natl Acad Sci U S A. 1993 Jun 15;90(12):5791–5795. doi: 10.1073/pnas.90.12.5791. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Dunn B. E., Cohen H., Blaser M. J. Helicobacter pylori. Clin Microbiol Rev. 1997 Oct;10(4):720–741. doi: 10.1128/cmr.10.4.720. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Graham D. Y., de Boer W. A., Tytgat G. N. Choosing the best anti-Helicobacter pylori therapy: effect of antimicrobial resistance. Am J Gastroenterol. 1996 Jun;91(6):1072–1076. [PubMed] [Google Scholar]
  11. Kuipers E. J., Pérez-Pérez G. I., Meuwissen S. G., Blaser M. J. Helicobacter pylori and atrophic gastritis: importance of the cagA status. J Natl Cancer Inst. 1995 Dec 6;87(23):1777–1780. doi: 10.1093/jnci/87.23.1777. [DOI] [PubMed] [Google Scholar]
  12. Labenz J., Leverkus F., Börsch G. Omeprazole plus amoxicillin for cure of Helicobacter pylori infection. Factors influencing the treatment success. Scand J Gastroenterol. 1994 Dec;29(12):1070–1075. doi: 10.3109/00365529409094890. [DOI] [PubMed] [Google Scholar]
  13. Lai J. Y., De Boer W. A., Driessen W. M., Geuskens L. M. Long-term follow-up after cure of Helicobacter pylori infection with 4 days of quadruple therapy. Aliment Pharmacol Ther. 1996 Aug;10(4):645–650. doi: 10.1046/j.1365-2036.1996.43185000.x. [DOI] [PubMed] [Google Scholar]
  14. Leunk R. D. Production of a cytotoxin by Helicobacter pylori. Rev Infect Dis. 1991 Jul-Aug;13 (Suppl 8):S686–S689. doi: 10.1093/clinids/13.supplement_8.s686. [DOI] [PubMed] [Google Scholar]
  15. Mobley H. L. Defining Helicobacter pylori as a pathogen: strain heterogeneity and virulence. Am J Med. 1996 May 20;100(5A):2S–11S. doi: 10.1016/s0002-9343(96)80223-3. [DOI] [PubMed] [Google Scholar]
  16. Taylor D. N., Blaser M. J. The epidemiology of Helicobacter pylori infection. Epidemiol Rev. 1991;13:42–59. doi: 10.1093/oxfordjournals.epirev.a036078. [DOI] [PubMed] [Google Scholar]
  17. Tucci A., Poli L., Paparo G. F., Bocus P., Togliani T., Mazzoni C., Orcioni G. F., Agosti R., Grigioni W. F., Sottili S. Weekend therapy for the treatment of Helicobacter pylori infection. Am J Gastroenterol. 1998 May;93(5):737–742. doi: 10.1111/j.1572-0241.1998.216_a.x. [DOI] [PubMed] [Google Scholar]
  18. Van Doorn L. J., Figueiredo C., Mégraud F., Pena S., Midolo P., Queiroz D. M., Carneiro F., Vanderborght B., Pegado M. D., Sanna R. Geographic distribution of vacA allelic types of Helicobacter pylori. Gastroenterology. 1999 Apr;116(4):823–830. doi: 10.1016/s0016-5085(99)70065-x. [DOI] [PubMed] [Google Scholar]
  19. Weel J. F., van der Hulst R. W., Gerrits Y., Roorda P., Feller M., Dankert J., Tytgat G. N., van der Ende A. The interrelationship between cytotoxin-associated gene A, vacuolating cytotoxin, and Helicobacter pylori-related diseases. J Infect Dis. 1996 May;173(5):1171–1175. doi: 10.1093/infdis/173.5.1171. [DOI] [PubMed] [Google Scholar]
  20. de Boer W. A., Tytgat G. N. The best therapy for Helicobacter pylori infection: should efficacy or side-effect profile determine our choice? Scand J Gastroenterol. 1995 May;30(5):401–407. doi: 10.3109/00365529509093298. [DOI] [PubMed] [Google Scholar]
  21. de Boer W. A., van Etten R. J., Coremans A., Schneeberger P. M. Two-day 'weekend' lansoprazole-quadruple therapy for Helicobacter pylori infection. Aliment Pharmacol Ther. 1998 Jan;12(1):77–81. doi: 10.1046/j.1365-2036.1998.00266.x. [DOI] [PubMed] [Google Scholar]
  22. de Boer W. A., van Etten R. J., Schade R. W., Ouwehand M. E., Schneeberger P. M., van Unnik A. J., Tytgat G. N. One-day intensified lansoprazole-quadruple therapy for cure of Helicobacter pylori infection. Aliment Pharmacol Ther. 1997 Feb;11(1):109–112. doi: 10.1046/j.1365-2036.1997.121292000.x. [DOI] [PubMed] [Google Scholar]
  23. van Doorn L. J., Figueiredo C., Rossau R., Jannes G., van Asbroek M., Sousa J. C., Carneiro F., Quint W. G. Typing of Helicobacter pylori vacA gene and detection of cagA gene by PCR and reverse hybridization. J Clin Microbiol. 1998 May;36(5):1271–1276. doi: 10.1128/jcm.36.5.1271-1276.1998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. van Doorn L. J., Figueiredo C., Sanna R., Pena S., Midolo P., Ng E. K., Atherton J. C., Blaser M. J., Quint W. G. Expanding allelic diversity of Helicobacter pylori vacA. J Clin Microbiol. 1998 Sep;36(9):2597–2603. doi: 10.1128/jcm.36.9.2597-2603.1998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. van Doorn L. J., Figueiredo C., Sanna R., Plaisier A., Schneeberger P., de Boer W., Quint W. Clinical relevance of the cagA, vacA, and iceA status of Helicobacter pylori. Gastroenterology. 1998 Jul;115(1):58–66. doi: 10.1016/s0016-5085(98)70365-8. [DOI] [PubMed] [Google Scholar]
  26. van der Hulst R. W., Weel J. F., Verheul S. B., Keller J. J., ten Kate F. J., van der Ende A., Rauws E. A., Dankert J., Tytgat G. N. Treatment of Helicobacter pylori infection with low or high dose omeprazole combined with amoxycillin and the effect of early retreatment. Aliment Pharmacol Ther. 1996 Apr;10(2):165–171. doi: 10.1046/j.1365-2036.1996.715895000.x. [DOI] [PubMed] [Google Scholar]

Articles from Gut are provided here courtesy of BMJ Publishing Group

RESOURCES