Helicobacter pylori is a motile, Gram-negative, curved or spiral bacillus. It was originally named Campylobacter pyloridis. It was then renamed C. pylori and later H. pylori, as its structure became better identified.
The full genetic code of H. pylori is now known.Specific genotypes are associated with severe morbidity. The most prevalent genotypes in patients with peptic ulcerations are vacA-positive and cagA-positive.
The presence of vacA, cagA and other strains of H. pylori is strongly associated with intestinal-type gastric cancer.
- The prevalence of H. pylori in many areas of the UK is lower than 15% and continues to fall.
- A Belgian study found the lowest prevalence in residents of Western European origin and the highest prevalence in those of North African origin.
- As a general rule, the prevalence of H. pylori increases with age.
- Globally, more than 50% of all people are infected.
Sequelae of Helicobacter pylori infection
More than 50% of the world's population are infected with H. pylori, so infection is not invariably associated with disease.However, it is present in almost all cases of duodenal ulcer and most cases of gastric ulcer. The recognition of the association between H. pylori infection and peptic ulcer disease was a major breakthrough in gastroenterology. Peptic ulcer is rare without either H. pylori or non-steroidal anti-inflammatory drugs (NSAIDs).There has been some debate about whether H. pylori is a cause of duodenal ulcer or whether the two are simply associated. There is a considerable weight of evidence supporting the latter, including the finding that a high proportion of children who have duodenal ulcer disease test positive for H. pylori.
H. pylori-positive patients have at least a six-fold greater risk of developing gastric adenocarcinoma than do those without infection.
Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is a rare but interesting condition in that eradication of H. pylori causes clinical regression of the lymphoma in 75% of cases.In the remaining 25%, there appears to be translocation of genes with oncogenic properties.
The association between H. pylori infection and gastro-oesophageal reflux disease remains controversial. In fact some studies suggest that there is an inverse relationship and that its presence may confer a protective effect against reflux oesophagitis.
H. pylori infection may be asymptomatic - as above.
There may be symptoms of peptic ulcer disease (dyspepsia) - eg, fullness, bloating, early satiety and nausea.
Patients aged 55 years and older with unexplained and persistent recent-onset dyspepsia alone should also have endoscopy.
- Review medications for possible causes of dyspepsia - eg, calcium antagonists, nitrates, theophyllines, bisphosphonates, corticosteroids and NSAIDs. In patients requiring referral, suspend NSAID use. Consider the possibility of cardiac or biliary disease as part of the differential diagnosis.
- Either empirical treatment for four weeks with a full-dose proton pump inhibitor (PPI) or testing for and treating H. pylori may be employed. Current evidence offers no guidance on preference.
- A two-week washout period following PPI use is necessary before testing for H. pylori with a breath test or a stool antigen test.
- If there is failure to resolve, or relapse on stopping acid suppression, evidence suggests testing and treating H. pylori if the test is positive.
- H. pylori eradication therapy without testing first is not recommended and is likely to be very wasteful of resources, especially as this is likely to cause some dilemma if the patient returns with symptoms.
- Eradication of H. pylori in patients who are about to start NSAIDs substantially reduces the risk of endoscopic and complicated ulcers.
Testing for Helicobacter pylori
Non-invasive testing is useful only if it will alter the subsequent management of the patient. The National Institute for Health and Care Excellence (NICE) offers advice on which test to use:
- 13C urea breath tests or stool antigen tests are the recommended way of testing for H. pylori, although laboratory-based serology can be used if locally validated. Stop antisecretories or bismuth two weeks before the test.
- The breath test is the only currently validated method for assessing eradication in primary care.
Offer eradication therapy to all patients with positive tests for H. pylori.
There are several regimes. There is probably no difference between the various PPIs available, provided that they are used at the equivalent dose and this is a matter of personal choice.
|Recommended first-line regimes|
|These are optimum regimes on current evidence:|
|Second-line H. pylori eradication regimes|
If there is failure of treatment, this is usually due to poor compliance or to antibiotic resistance:
- If there was poor compliance, a more tolerable regime may be required. Abdominal discomfort and diarrhoea are very common but the patient should be encouraged to persist to achieve eradication.
- Resistance can even develop during treatment, especially with a single antibiotic.
- Metronidazole and clarithromycin are the antibiotics most implicated in resistance; resistance rates vary across the UK.
It would be reasonable to have local protocols based upon local patterns of antibiotic resistance.Resistance to metronidazole (in particular) is highly variable.
- The Health Protection Agency reports that the prevalence of H. pylori antibiotic resistance varies within the UK depending on location. It is around 20-63% for metronidazole and 4.4-11% for clarithromycin.
- Metronidazole resistance is low in rural areas within the UK but can be as high as 65% in urban areas with large immigrant populations.
- Amoxicillin resistance is rare but does occur.
- Resistance can be acquired during treatment.
Patients who are not cured with two consecutive treatments, including clarithromycin and metronidazole, will have at least single and usually double resistance. No standard third-line therapy exists, although isolated studies have reported success with a PPI, bismuth subcitrate, tetracycline and metronidazole.Seek specialist advice if second-line therapy fails. European guidelines recommend culture before treatment based on the microbial antibiotic sensitivity in such circumstances.
Benefits of treatment
- There is definitive evidence that eradicating H. pylori improves remission rates for gastric and duodenal ulcers and is superior and more cost-effective than maintenance acid suppressive therapy in preventing duodenal ulcer.
- One study found that H. pylori eradication was more successful in decreasing recurrent gastroduodenal ulcer bleeding than ulcer healing treatment alone.
- H. pylori eradication is beneficial in patients with dyspepsia who have been identified as H. pylori-positive but have not had an endoscopy ('test and treat').
- H. pylori eradication has been proposed as first-line treatment for infected patients with stage I low-grade gastric MALT lymphoma.
- The evidence concerning the protective effect of H.pylori against gastric carcinoma is complex but the consensus is that it should be eradicated as soon as possible and best before pre-cancerous lesions are present.
- Re-infection rates are variable. One study reported a re-infection rate of 1.8%. Developed countries had lower re-infection rates compared with those of developing countries.
- In dyspepsia it is only necessary to check for H. pylori eradication in patients whose symptoms return.
- Patients with peptic ulcer should have a re-test (gastric or duodenal) six to eight weeks after beginning treatment.
- Serology can remain positive for up to one year after eradication.
- If the patient was taking NSAIDs it will be necessary to discuss further management.
- Low-dose misoprostol is less effective than acid suppression.
See separate Peptic Ulcer Disease article for details concerning the management of non-healing ulcers.
- Studies suggest that probiotics and lactobacilli reduce the activity of H. pylori.
- It is generally advocated that H. pylori testing should be driven purely to confirm an infection as the cause of disease and then to eradicate it.
- The risk:benefit ratio of H. pylori eradication in asymptomatic patients requires further evaluation. A large trial of Asian patients provided moderate evidence that eradication reduced the risk of gastric carcinoma but studies of patients from other ethnic communities are required.
- H. pylori infection has been implicated in the aetiology of coronary heart disease but this has recently been refuted.Likewise, evidence linking cirrhosis, gastroduodenal ulcers and H. pylori is lacking.
There is also ongoing work to produce a vaccine against the organism.
Further reading and references
Parente F, Maconi G, Sangaletti O, et al; Prevalence of Helicobacter pylori infection and related gastroduodenal lesions in spouses of Helicobacter pylori positive patients with duodenal ulcer. Gut. 1996 Nov39(5):629-33.
Su J, Zhou XY, Zhang GX; Association between Helicobacter pylori infection and migraine: A meta-analysis. World J Gastroenterol. 2014 Oct 2820(40):14965-72. doi: 10.3748/wjg.v20.i40.14965.
Sweeney EG, Guillemin K; A gastric pathogen moves chemotaxis in a new direction. MBio. 2011 Sep 202(5). pii: e00201-11. doi: 10.1128/mBio.00201-11. Print 2011.
Oh JD, Kling-Backhed H, Giannakis M, et al; The complete genome sequence of a chronic atrophic gastritis Helicobacter pylori strain: evolution during disease progression. Proc Natl Acad Sci U S A. 2006 Jun 27103(26):9999-10004. Epub 2006 Jun 20.
Memon AA, Hussein NR, Miendje Deyi VY, et al; Vacuolating cytotoxin genotypes are strong markers of gastric cancer and duodenal ulcer-associated Helicobacter pylori strains: a matched case-control study. J Clin Microbiol. 2014 Aug52(8):2984-9. doi: 10.1128/JCM.00551-14. Epub 2014 Jun 11.
Testerman TL, Morris J; Beyond the stomach: An updated view of pathogenesis, diagnosis, and treatment. World J Gastroenterol. 2014 Sep 2820(36):12781-12808.
Miendje Deyi VY, Vanderpas J, Bontems P, et al; Marching cohort of Helicobacter pylori infection over two decades (1988-2007): combined effects of secular trend and population migration. Epidemiol Infect. 2011 Apr139(4):572-80. doi: 10.1017/S095026881000110X. Epub 2010 Jun 7.
Hunt RH, Xiao SD, Megraud F, et al; Helicobacter pylori in developing countries. World Gastroenterology Organisation Global Guideline. J Gastrointestin Liver Dis. 2011 Sep20(3):299-304.
Rizwan M, Fatima N, Alvi A; Epidemiology and pattern of antibiotic resistance in Helicobacter pylori: scenario from Saudi Arabia. Saudi J Gastroenterol. 2014 Jul-Aug20(4):212-8. doi: 10.4103/1319-3767.136935.
Yeomans ND; The ulcer sleuths: The search for the cause of peptic ulcers. J Gastroenterol Hepatol. 2011 Jan26 Suppl 1:35-41. doi:
Hernandez C, Serrano C, Einisman H, et al; Peptic Ulcer Disease in Helicobacter Pylori-Infected Children: Clinical Findings and Mucosal Immune Response. J Pediatr Gastroenterol Nutr. 2014 Jul 21.
Hartgrink HH, Jansen EP, van Grieken NC, et al; Gastric cancer. Lancet. 2009 Aug 8374(9688):477-90. Epub 2009 Jul 20.
Zullo A, Hassan C, Ridola L, et al; Gastric MALT lymphoma: old and new insights. Ann Gastroenterol. 201427(1):27-33.
Isaacson PG, Du MQ; Gastric lymphomas: genetics and resistance to H. pylori eradication. Verh Dtsch Ges Pathol. 200387:116-22.
Nam SY; Helicobacter pylori Has an Inverse Relationship With Severity of Reflux J Neurogastroenterol Motil. 2011 Jul17(3):209-10. Epub 2011 Jul 13.
Referral for suspected cancer; NICE Clinical Guideline (2005)
Delaney BC, Moayyedi P, Forman D; Initial management strategies for dyspepsia. Cochrane Database Syst Rev. 2003(2):CD001961.
Should You Eradicate Helicobacter Pylori Prior to Chronic NSAID Treatment?; Clinical Correlations, 2011
Surveillance of Helicobacter pylori antibiotic resistance in England and Wales; Public Health England, 2008
Cameron EA, Powell KU, Baldwin L, et al; Helicobacter pylori: antibiotic resistance and eradication rates in Suffolk, UK, 1991-2001. J Med Microbiol. 2004 Jun
Gisbert JP, Perez-Aisa A, Rodrigo L, et al; Third-line rescue therapy with bismuth-containing quadruple regimen after failure of two treatments (with clarithromycin and levofloxacin) for H. pylori infection. Dig Dis Sci. 2014 Feb59(2):383-9. doi: 10.1007/s10620-013-2900-x. Epub 2013 Oct 15.
Suzuki H, Nishizawa T, Hibi T; Helicobacter pylori eradication therapy. Future Microbiol. 2010 Apr5(4):639-48.
Hung IF, Wong BC; Assessing the risks and benefits of treating Helicobacter pylori infection. Therap Adv Gastroenterol. 2009 May2(3):141-7. doi: 10.1177/1756283X08100279.
Silva FM, Navarro-Rodriguez T, Barbuti RC, et al; Helicobacter pylori reinfection in Brazilian patients with peptic ulcer disease: Helicobacter. 2010 Feb15(1):46-52.
de Vrese M, Kristen H, Rautenberg P, et al; Probiotic lactobacilli and bifidobacteria in a fermented milk product with added J Dairy Res. 2011 Nov78(4):396-403. Epub 2011 Aug 26.
Ford AC, Forman D, Hunt RH, et al; Helicobacter pylori eradication therapy to prevent gastric cancer in healthy asymptomatic infected individuals: systematic review and meta-analysis of randomised controlled trials. BMJ. 2014 May 20348:g3174. doi: 10.1136/bmj.g3174.
Christodoulou DK, Milionis HJ, Pappa P, et al; Association of Helicobacter pylori infection with cardiovascular disease--is it Eur J Intern Med. 2011 Apr22(2):191-4. Epub 2010 Dec 23.
Kirchner GI, Beil W, Bleck JS, et al; Prevalence of Helicobacter pylori and occurrence of gastroduodenal lesions in Int J Clin Exp Med. 20114(1):26-31. Epub 2010 Dec 25.
Aebischer T, Meyer TF, Andersen LP; Inflammation, immunity, and vaccines for Helicobacter. Helicobacter. 2010 Sep15 Suppl 1:21-8. doi: 10.1111/j.1523-5378.2010.00777.x.
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