H. pylori treatment – Mnemonic
Helicobacter pylori, previously named Campylobacter pyloridis, is a Gram-negative, microaerophilic bacterium found in the stomach. It was identified in 1982 by Barry Marshall and Robin Warren, who found that it was present in patients with chronic gastritis and gastric ulcers, conditions that were not previously believed to have a microbial cause. It is also linked to the development of duodenal ulcers and stomach cancer. However, over 80 percent of individuals infected with the bacterium are asymptomatic and it has been postulated that it may play an important role in the natural stomach ecology.
More than 50% of the world’s population harbor H. pylori in their upper gastrointestinal tract. Infection is more prevalent in developing countries, and incidence is decreasing in Western countries. H. pylori’s helix shape (from which the generic name is derived) is thought to have evolved to penetrate the mucoid lining of the stomach.
Signs and Symptoms:
Over 80% of people infected with H. pylori show no symptoms. Acute infection may appear as an acute gastritis with abdominal pain (stomach ache) or nausea. Where this develops into chronic gastritis, the symptoms, if present, are often those of non-ulcer dyspepsia: stomach pains, nausea, bloating, belching, and sometimes vomiting or black stool.
Individuals infected with H. pylori have a 10 to 20% lifetime risk of developing peptic ulcers and a 1 to 2% risk of acquiring stomach cancer. Inflammation of the pyloric antrum is more likely to lead to duodenal ulcers, while inflammation of the corpus (body of the stomach) is more likely to lead to gastric ulcers and gastric carcinoma. However, it is possible that H. pylori plays a role only in the first stage that leads to common chronic inflammation, but not in further stages leading to carcinogenesis.
H. pylori is a helix-shaped (classified as a curved rod, not spirochaete) Gram-negative bacterium. It is microaerophilic; that is, it requires oxygen, but at lower concentration than is found in the atmosphere. It contains a hydrogenase which can be used to obtain energy by oxidizing molecular hydrogen (H2) produced by intestinal bacteria. It produces oxidase, catalase, and urease. It is capable of forming biofilms and can convert from spiral to a possibly viable but nonculturable coccoid form, both likely to favor its survival and be factors in the epidemiology of the bacterium.
To colonize the stomach, H. pylori must survive the acidic pH of the lumen and use its flagella to burrow into the mucus to reach its niche, close to the stomach’s epithelial cell layer. Many bacteria can be found deep in the mucus, which is continuously secreted by mucus-secreting cells and removed on the luminal side. To avoid being carried into the lumen, H. pylori senses the pH gradient within the mucus layer by chemotaxis and swims away from the acidic contents of the lumen towards the more neutral pH environment of the epithelial cell surface. H. pylori is also found on the inner surface of the stomach epithelial cells and occasionally inside epithelial cells. H. pylori produces large amounts of the enzyme urease, molecules of which are localized inside and outside of the bacterium. Urease breaks down urea (which is normally secreted into the stomach) to carbon dioxide and ammonia. The ammonia is converted to ammonium by accepting a proton (H+), which neutralizes gastric acid. The survival of H. pylori in the acidic stomach is dependent on urease. The ammonia produced is toxic to the epithelial cells, and, along with the other products of H. pylori—including proteases, vacuolating cytotoxin A (VacA), and certain phospholipases,— damages those cells.
Colonization of the stomach by H. pylori results in chronic gastritis, an inflammation of the stomach lining. The severity of the inflammation is likely to underlie H. pylori-related diseases. Duodenal and stomach ulcers result when the consequences of inflammation allow the acid and pepsin in the stomach lumen to overwhelm the mechanisms that protect the stomach and duodenal mucosa from these caustic substances. The type of ulcer that develops depends on the location of chronic gastritis, which occurs at the site of H. pylori colonization.
Colonization with H. pylori is not a disease in and of itself but a condition associated with a number of disorders of the upper gastrointestinal tract. Testing for H. pylori is recommended if there is peptic ulcer disease, low grade gastric MALT lymphoma, after endoscopic resection of early gastric cancer, if there are first degree relatives with gastric cancer, and in certain cases of dyspepsia, not routinely. Several ways of testing exist. One can test noninvasively for H. pylori infection with a blood antibody test, stool antigen test, or with the carbon urea breath test. However, the most reliable method for detecting H. pylori infection is a biopsy check during endoscopy with a rapid urease test, histological examination, and microbial culture. There is also a urine ELISA test with a 96% sensitivity and 79% specificity. None of the test methods is completely failsafe. Even biopsy is dependent on the location of the biopsy. Blood antibody tests, for example, range from 76% to 84% sensitivity. Some drugs can affect H. pylori urease activity and give false negatives with the urea-based tests.
Once H. pylori is detected in a person with a peptic ulcer, the normal procedure is to eradicate it and allow the ulcer to heal. The standard first-line therapy is a one week “triple therapy” consisting of proton pump inhibitors such as omeprazole and the antibiotics clarithromycin and amoxicillin. Variations of the triple therapy have been developed over the years, such as using a different proton pump inhibitor, as with pantoprazole or rabeprazole, or replacing amoxicillin with metronidazole for people who are allergic to penicillin. Such a therapy has revolutionized the treatment of peptic ulcers and has made a cure to the disease possible; previously, the only option was symptom control using antacids, H2-antagonists or proton pump inhibitors alone.
An increasing number of infected individuals are found to harbor antibiotic-resistant bacteria. This results in initial treatment failure and requires additional rounds of antibiotic therapy or alternative strategies, such as a quadruple therapy, which adds a bismuth colloid, such as bismuth subsalicylate. For the treatment of clarithromycin-resistant strains of H. pylori, the use of levofloxacin as part of the therapy has been suggested.
- Blaser, M. J. (2006). “Who are we? Indigenous microbes and the ecology of human diseases”. EMBO Reports 7 (10): 956–60. doi:10.1038/sj.embor.7400812.PMC 1618379. PMID 17016449.
- Yamaoka, Yoshio (2008). Helicobacter pylori: Molecular Genetics and Cellular Biology. Caister Academic Pr. ISBN 1-904455-31-X.
- Brown LM (2000). “Helicobacter pylori: epidemiology and routes of transmission”. Epidemiol Rev 22 (2): 283–97.doi:10.1093/oxfordjournals.epirev.a018040. PMID 11218379.
- Boyanova, L (editor) (2011). Helicobacter pylori. Caister Academic Press. ISBN 978-1-904455-84-4.
- Butcher, Graham P. (2003). Gastroenterology: An Illustrated Colour Text. Elsevier Health Sciences. p. 25. ISBN 0-443-06215-3.
- Butcher 2003, pp. 24–5 Ryan, Kenneth (2010). Sherris Medical Microbiology. McGraw-Hill. pp. 573, 576.ISBN 978-0-07-160402-4.
- Ryan, Kenneth (2010). Sherris Medical Microbiology. McGraw-Hill. pp. 573, 576.ISBN 978-0-07-160402-4.
- Kusters JG, van Vliet AH, Kuipers EJ (July 2006). “Pathogenesis ofHelicobacter pylori Infection”. Clin Microbiol Rev 19 (3): 449–90.doi:10.1128/CMR.00054-05. PMC 1539101. PMID 16847081.
- Suerbaum S, Michetti P (October 2002). “Helicobacter pylori infection”. N. Engl. J. Med.347 (15): 1175–86. doi:10.1056/NEJMra020542. PMID 12374879.
- Fuccio, L; Zagari, RM; Eusebi, LH; Laterza, L; Cennamo, V; Ceroni, L; Grilli, D; Bazzoli, F (2009). “Meta-analysis: can Helicobacter pylori eradication treatment reduce the risk for gastric cancer?”. Ann Intern Med 151 (2): 121–8. PMID 19620164.
- Olson JW, Maier RJ (November 2002). “Molecular hydrogen as an energy source forHelicobacter pylori“. Science 298 (5599): 1788–90. doi:10.1126/science.1077123.PMID 12459589.
- Stark RM, Gerwig GJ, Pitman RS et al. (February 1999). “Biofilm formation byHelicobacter pylori“. Lett Appl Microbiol 28 (2): 121–6. doi:10.1046/j.1365-2672.1999.00481.x. PMID 10063642.
- Chan WY, Hui PK, Leung KM, Chow J, Kwok F, Ng CS (October 1994). “Coccoid forms of Helicobacter pylori in the human stomach”. Am J Clin Pathol 102 (4): 503–7.PMID 7524304.
- Josenhans C, Eaton KA, Thevenot T, Suerbaum S (August 2000). “Switching of Flagellar Motility in Helicobacter pylori by Reversible Length Variation of a Short Homopolymeric Sequence Repeat in fliP, a Gene Encoding a Basal Body Protein”.Infect Immun 68 (8): 4598–603. doi:10.1128/IAI.68.8.4598-4603.2000. PMC 98385.PMID 10899861.
- Rust M, Schweinitzer T, Josenhans C (2008). “Helicobacter Flagella, Motility and Chemotaxis”. In Yamaoka Y. Helicobacter pylori: Molecular Genetics and Cellular Biology. Caister Academic Press. ISBN 1-904455-31-X.
- Tomb JF, White O, Kerlavage AR et al. (August 1997). “The complete genome sequence of the gastric pathogen Helicobacter pylori“. Nature 388 (6642): 539–47.doi:10.1038/41483. PMID 9252185.
- “Genome information for the H. pylori 26695 and J99 strains”. Institut Pasteur. 2002. Retrieved 2008-09-01.
- “Helicobacter pylori 26695, complete genome”. National Center for Biotechnology Information. Retrieved 2008-09-01.
- “Helicobacter pylori J99, complete genome”. National Center for Biotechnology Information. Retrieved 2008-09-01.
- Oh JD, Kling-Bäckhed H, Giannakis M et al. (June 2006). “The complete genome sequence of a chronic atrophic gastritis Helicobacter pylori strain: Evolution during disease progression”. Proc Natl Acad Sci U.S.A. 103 (26): 9999–10004.doi:10.1073/pnas.0603784103. PMC 1480403. PMID 16788065.
- Baldwin DN, Shepherd B, Kraemer P et al. (February 2007). “Identification ofHelicobacter pylori Genes That Contribute to Stomach Colonization”. Infect Immun 75(2): 1005–16. doi:10.1128/IAI.01176-06. PMC 1828534. PMID 17101654.
- Broutet N, Marais A, Lamouliatte H et al. (April 2001). “cagA Status and Eradication Treatment Outcome of Anti-Helicobacter pylori Triple Therapies in Patients with Nonulcer Dyspepsia”. J Clin Microbiol 39 (4): 1319–22. doi:10.1128/JCM.39.4.1319-1322.2001. PMC 87932. PMID 11283049.
- Amieva MR, El-Omar EM (January 2008). “Host-bacterial interactions in Helicobacter pylori infection”. Gastroenterology 134 (1): 306–23. doi:10.1053/j.gastro.2007.11.009.PMID 18166359.
- Schreiber S, Konradt M, Groll C et al. (April 2004). “The spatial orientation ofHelicobacter pylori in the gastric mucus”. Proc. Natl. Acad. Sci. U.S.A. 101 (14): 5024–9. doi:10.1073/pnas.0308386101. PMC 387367. PMID 15044704.
- Petersen AM, Krogfelt KA (May 2003). “Helicobacter pylori: an invading microorganism? A review”. FEMS Immunol. Med. Microbiol. 36 (3): 117–26.doi:10.1016/S0928-8244(03)00020-8. PMID 12738380.
- Ilver D, Arnqvist A, Ogren J et al. (January 1998). “Helicobacter pylori adhesin binding fucosylated histo-blood group antigens revealed by retagging”. Science 279 (5349): 373–7. doi:10.1126/science.279.5349.373. PMID 9430586.
- Smoot DT (December 1997). “How does Helicobacter pylori cause mucosal damage? Direct mechanisms”. Gastroenterology 113 (6 Suppl): S31–4; discussion S50.doi:10.1016/S0016-5085(97)80008-X. PMID 9394757.
- Dumrese C, Slomianka L, Ziegler U et al. (May 2009). “The secreted Helicobacter cysteine-rich protein A causes adherence of human monocytes and differentiation into a macrophage-like phenotype”. FEBS Letters 583 (10): 1637–43.doi:10.1016/j.febslet.2009.04.027. PMC 2764743. PMID 19393649.
- Shiotani A, Graham DY (November 2002). “Pathogenesis and therapy of gastric and duodenal ulcer disease”. Med. Clin. North Am. 86 (6): 1447–66, viii. doi:10.1016/S0025-7125(02)00083-4. PMID 12510460.
- Dixon MF (February 2000). “Patterns of inflammation linked to ulcer disease”. Baillieres Best Pract Res Clin Gastroenterol 14 (1): 27–40. doi:10.1053/bega.1999.0057.PMID 10749087.
- Blaser MJ, Atherton JC (February 2004). “Helicobacter pylori persistence: biology and disease”. J. Clin. Invest. 113 (3): 321–33. doi:10.1172/JCI20925.PMC 324548. PMID 14755326.
- Schubert ML, Peura DA (June 2008). “Control of gastric acid secretion in health and disease”. Gastroenterology 134 (7): 1842–60. doi:10.1053/j.gastro.2008.05.021.PMID 18474247.
- Suerbaum S, Michetti P (October 2002). “Helicobacter pylori infection”. N. Engl. J. Med.347 (15): 1175–86. doi:10.1056/NEJMra020542. PMID 12374879.
- Peek RM, Crabtree JE (January 2006). “Helicobacter infection and gastric neoplasia”. J. Pathol. 208 (2): 233–48. doi:10.1002/path.1868. PMID 16362989.
- Viala J, Chaput C, Boneca IG et al. (November 2004). “Nod1 responds to peptidoglycan delivered by the Helicobacter pylori cag pathogenicity island”. Nat. Immunol. 5 (11): 1166–74. doi:10.1038/ni1131. PMID 15489856.
- Backert S, Selbach M (August 2008). “Role of type IV secretion in Helicobacter pyloripathogenesis”. Cell. Microbiol. 10 (8): 1573–81. doi:10.1111/j.1462-5822.2008.01156.x. PMID 18410539.
- Hatakeyama, M (Sep. 2004). “Oncogenic mechanisms of the Helicobacter pylori CagA protein”. Nat Rev Cancer (United States) 4 (9): 688–94. doi:10.1038/nrc1433.PMID 15343275.
- Tsuji S, Kawai N, Tsujii M, Kawano S, Hori M (July 2003). “Review article: inflammation-related promotion of gastrointestinal carcinogenesis–a perigenetic pathway”. Aliment. Pharmacol. Ther. 18 (Suppl 1): 82–9. doi:10.1046/j.1365-2036.18.s1.22.x.PMID 12925144.
- Suganuma M, Yamaguchi K, Ono Y et al. (July 2008). “TNF-α-inducing protein, a carcinogenic factor secreted from H. pylori, enters gastric cancer cells”. Int. J. Cancer 123(1): 117–22. doi:10.1002/ijc.23484. PMID 18412243.
- Stenström B, Mendis A, Marshall B (August 2008). “Helicobacter pylori—The latest in diagnosis and treatment”. Aust Fam Physician 37 (8): 608–12. PMID 18704207.
- Logan RP, Walker MM (October 2001). “Epidemiology and diagnosis of Helicobacter pylori infection”. BMJ 323 (7318): 920–2. doi:10.1136/bmj.323.7318.920.PMC 1121445. PMID 11668141.
- Selgrad M, Malfertheiner P (June 2008). “New strategies for Helicobacter pylorieradication”. Curr Opin Pharmacol 8 (5): 593–7. doi:10.1016/j.coph.2008.04.010.PMID 18555746.
- Hoffelner H, Rieder G, Haas R (January 2008). “Helicobacter pylori vaccine development: optimisation of strategies and importance of challenging strain and animal model”. Int. J. Med. Microbiol. 298 (1–2): 151–9. doi:10.1016/j.ijmm.2007.07.006.PMID 17714988.
- Kabir S (April 2007). “The current status of Helicobacter pylori vaccines: a review”.Helicobacter 12 (2): 89–102. doi:10.1111/j.1523-5378.2007.00478.x.PMID 17309745.
- Malfertheiner P, Schultze V, Rosenkranz B et al. (May 2008). “Safety and Immunogenicity of an Intramuscular Helicobacter pylori Vaccine in Noninfected Volunteers: A Phase I Study”. Gastroenterology 135 (3): 787–95.doi:10.1053/j.gastro.2008.05.054. PMID 18619971.
- Malfertheiner, P; Megraud, F; O’Morain, CA; Atherton, J; Axon, AT; Bazzoli, F; Gensini, GF; Gisbert, JP; Graham, DY; Rokkas, T; El-Omar, EM; Kuipers, EJ; European Helicobacter Study, Group (2012 May). “Management of Helicobacter pylori infection—the Maastricht IV/ Florence Consensus Report”. Gut 61 (5): 646–64. doi:10.1136/gutjnl-2012-302084. PMID 22491499.
- Malfertheiner P, Megraud F, O’Morain C et al. (June 2007). “Current concepts in the management of Helicobacter pylori infection: the Maastricht III Consensus Report”. Gut56 (6): 772–81. doi:10.1136/gut.2006.101634. PMC 1954853. PMID 17170018.
- Rauws EA, Tytgat GN (May 1990). “Cure of duodenal ulcer associated with eradication of Helicobacter pylori“. Lancet 335 (8700): 1233–5. doi:10.1016/0140-6736(90)91301-P. PMID 1971318.
- Graham DY, Lew GM, Evans DG, Evans DJ, Klein PD (August 1991). “Effect of triple therapy (antibiotics plus bismuth) on duodenal ulcer healing. A randomized controlled trial”. Ann. Intern. Med. 115 (4): 266–9. PMID 1854110.
- Fischbach L, Evans EL (August 2007). “Meta-analysis: the effect of antibiotic resistance status on the efficacy of triple and quadruple first-line therapies for Helicobacter pylori“.Aliment. Pharmacol. Ther. 26 (3): 343–57. doi:10.1111/j.1365-2036.2007.03386.x.PMID 17635369.
- Graham DY, Shiotani A (June 2008). “Newer concepts regarding resistance in the treatment Helicobacter pylori infections”. Nat Clin Pract Gastroenterol Hepatol 5 (6): 321–31. doi:10.1038/ncpgasthep1138. PMC 2841357. PMID 18446147.
- Perna F, Zullo A, Ricci C, Hassan C, Morini S, Vaira D (November 2007). “Levofloxacin-based triple therapy for Helicobacter pylori re-treatment: role of bacterial resistance”. Dig Liver Dis 39 (11): 1001–5. doi:10.1016/j.dld.2007.06.016. PMID 17889627.
- Hsu PI, Wu DC, Chen A et al. (June 2008). “Quadruple rescue therapy for Helicobacter pylori infection after two treatment failures”. Eur. J. Clin. Invest. 38 (6): 404–9.doi:10.1111/j.1365-2362.2008.01951.x. PMID 18435764.