Helicobacter pylori infection
Helicobacter pylori is a major human pathogen that infects the stomach and produces inflammation that is responsible for various gastrointestinal diseases ( Yamaoka 2012 )
How common-H.pylori is a small curved highly motile gram negative microaerophilic bacterium that colonises the mucus layer of the human stomach Found in 1982 ( Warren and Marshall ) Very common bacterium and about 50 % of the world population is estimated to be infected ( extremely successful huma pathogen ) Prevalence is highly variable – it ranges between 85 % and 95 % in developing countries and between 30 and 50 % in developed world Most infections occur during childhood and rates of infection decrease with improvements in hygiene practices
Transmission -Humans are the principal reservoir Infection is usually acquired during childhood and persists unless antimicrobial Rx is given Likely routes of transmission are ○ faeco- oral ○ oro-oral ( through vomitus or saliva ) ○ intrafamilial ○ waterborne transmission Person to person transmission in early life is thought to be the most common mode H.pylori is an occupational hazard for gastroenterologists who perform endoscopies Most individuals are asymptomatic and the infection persists lifelong Infection with one strain of H pylori does not protect against future co-infections with another strain and no two strains are identical ( ie demonstrates genetic heterogeneity which is strain to strain genetic variability )
Pathogenesis -Pathogenesis and disease outcomes are mediated by a complex interplay between bacterial virulence factors , host and environmental factors Various ○ enzymes ( urease , catalase , lipase , phospholipase and proteases ) ○ vacuolating cytotoxin -product of expression of the vacA gene ○ immunogenic protein CagA , encoded by the CagA gene localised in the H. pylori pathogenicity island Recognised as an established causative agent of chronic inflammation of the mucous membranes of the stomach and of peptic ulcer Four steps determine the successful colonization of bacteria once it enters stomach 1 survival in acidic stomach 2 movement toward epithelium cells by flagella mediated motility 3 attachment to host cells by adhesin / receptors interaction 4 tissue damage by toxin
Risk factors -Age ( prevalence ↑ es with age ) Socioeconomic status Inadequate sanitation practices Crowded or high density living conditions Family h/o peptic ulcer Tobacco /alcohol use have not been found to be risk factors of H.pylori infection.
Likely protective factors -Adequate nutritional status Frequent consumption of fruits and vegetable Vitamin C.
Why important -With long term colonization H.pylori can damage the gastric mucosa and cause several diseases of the upper GI tract as ○ chronic gastritis ○ peptic ulcer ○ gastric malignancies as gastric cancer and gastric mucosa-associated lymphoid tissue ( MALT ) lymphoma Recognised as a Class I carcinogen by the International Agency for Research on Cancer – one of the strongest known risk factors for gastric malignancies BMJ quotes that about 15 % of infected individuals will develop peptic ulcer ( duodenal or gastric ) due to long term H. pylori colonization Also associated with several extra- digestive diseases as ○ iron deficiency anaemia ○ idiopathic thrombocytopenic purpura ○ risk of CV disease and lung cancer ( uncertain association ) H pylori colonization is associated with reduced risk of asthma and allergy.
Gastric cancer -Third leading cause of cancer death worldwide in both sexes ,fifth most common cancer worldwide Most cases are a linked to infection with H.pylori Other possible risk factors include ○ high salt and low fibre diet ○ exposure to N-nitroso compounds from diet or smoking ○ alcohol consumption ○ low socioeconomic status ○ high BMI ○ old age ○ previous gastric surgery Factors which play a role include ○ age at the acquisition of infection ○ the type of H.pylori strain ○ genetic profile of the host ○ environmental factors H.pylori infection is estimated to confer an individual lifetime risk of gastric cancer of 1% to 2 % irrespective of the population prevalence.
Indications for testing –patient with uncomplicated dyspepsia and no ALARM symptoms who are unresponsive to lifestyle changes and atacids , following a single 1 month Rx course with a PPI patients considered to be high risk of H .pylori infection for e.g older people , from N African ethnicity and those living in high risk areas , should be tested first or in parallel with a course of a PPI previously untested patients with a h/o peptic ulcers or bleeds patients with unexplained IDA after endoscopic investigation has excluded malignancy and other causes have been investigated
Invasive -rapid urease test histology culture PCR
Non-invasive serological tests stool antigen test urea breath test.
Stool antigen test -Non-invasive and less expensive -easy to use Two types ○ based on enzyme immunoassay ( EIA ) ○ immunochromatographic. Designed to identify current infection by detecting antigen (s) that are produced by live H. pylori bacteria and shed into the stool Containers provided by practice Advice to use disposable rubber or plastic gloves Avoid contamination with urine or water The sample should be fresh Can be used for identification of H.pylori in children Sensitivities and specificity can be similar to those of the 13C-urea breath test ie > 90 % False negative results can be seen if the patients are on PPIs or bismuth compounds as they inhibit H.pylori within the last 14 days
Urea breath test -solution of urea labeled with carbon-13 will be rapidly hydrolysed by the urease enzyme of H pylori detects current infection and is not radioactive relatively expensive but most accurate test patients need to fast before the test ( nor recommended for children and pregnant women ) patient provide a base sample and then consume a drink containing 13C enriched urea ( about 100 mls ) and after 30 mins blow into a 2nd tube – both samples are sent away for carbon dioxide isotope analysis by mass spectrometry and the result usually is available within a week
The American Gastroenterology Association recommends both SAT and UBT for the diagnosis of H.pylori infection in patients with dyspepsia.
Retesting for H pylori -Retesting should be done atleast 4 weeks after eradication therapy Functional dyspepsia – routine retesting not recommended. Consider for those who would value the information Poor compliance or area of high local resistance Persistent symptoms and initial test was done within 2 weeks of treatment with a PPI or within 4 weeks of antibacterial treatment Associated peptic ulcer , MALT lymphoma or after resection of an early gastric carcinoma Patient on aspirin without PPI cover Patients with severe persistent or recurrent symptoms , particularly if not typical of gastro-oeseophageal reflux disease.
Eradication triple therapy-Eradication is cost effective and dramatically alters the natural hx of gastritis and prevents its sequelae Increasing antibiotic resistance globally is a concern ( ask about previous antibiotic exposure )
Despite use of |current most effective treatment regimens about 1o% to 20 % of patients will fail to achieve eradication and will remain H.Pylori positive
H.pylori and NSAIDs act synergistic ally to increase the risk of ulcer and bleeding
About 20 % of those with H.pylori infection will experience an H.pylori related clinical disease
H pylori is not a major risk factor for all cause mortality
Guts UK 12 page excellent leaflet on H Pylori https://gutscharity.org.uk/wp-content/uploads/2019/01/Guts-UK-Helicobacter-pylori-Leaflet.pdf
Airdale NHS Trust’s leaflet on H Pylori 8 pages http://www.airedale-trust.nhs.uk/wp/wp-content/uploads/2018/10/Helicobacter-Pylori-Patient-Information-Leaflet.pdf
National Institute of Health ( NIH ) H Pylori and cancer https://www.cancer.gov/about-cancer/causes-prevention/risk/infectious-agents/h-pylori-fact-sheet
Auto-Downloads a pdf for the patient – stool test for H Pylori https://www.royalwolverhampton.nhs.uk/EasySiteWeb/GatewayLink.aspx?alId=5235
- Chen, Yu et al. “Association between Helicobacter pylori and mortality in the NHANES III study.” Gut vol. 62,9 (2013): 1262-9. doi:10.1136/gutjnl-2012-303018
- Effects of Helicobacter pylori treatment and vitamin and garlic supplementation on gastric cancer incidence and mortality: follow-up of a randomized intervention trial
- Ishaq, Sauid, and Lois Nunn. “Helicobacter pylori and gastric cancer: a state of the art review.” Gastroenterology and hepatology from bed to bench vol. 8,Suppl 1 (2015): S6-S14.
- BNF Helicobacter pylori infection https://bnf.nice.org.uk/treatment-summary/helicobacter-pylori-infection.html
Epidemiology, clinical impacts and current clinical management of Helicobacter pylori infection Hazel Mitchell and Peter Katelaris Med J Aust 2016; 204 (10): 376-380. || doi: 10.5694/mja16.00104
H. pylori Stool Antigen Testing Techlab via H. pylori Stool Antigen Testing – TECHLAB, Inc.
- Khoder, Ghalia et al. “Prevalence of Helicobacter pylori and Its Associated Factors among Healthy Asymptomatic Residents in the United Arab Emirates.” Pathogens (Basel, Switzerland) vol. 8,2 44. 1 Apr. 2019, doi:10.3390/pathogens8020044
- Brown LM. Helicobacter pylori: epidemiology and routes of transmission. Epidemiol Rev. 2000;22(2):283-97. doi: 10.1093/oxfordjournals.epirev.a018040. PMID: 11218379. ( Abstract )
- Kusters, Johannes G et al. “Pathogenesis of Helicobacter pylori infection.” Clinical microbiology reviews vol. 19,3 (2006): 449-90. doi:10.1128/CMR.00054-05
- Cheng-Yen Kao, Bor-Shyang Sheu, Jiunn-Jong Wu,
Helicobacter pylori infection: An overview of bacterial virulence factors and pathogenesis,
Biomedical Journal, Volume 39, Issue 1, 2016, Pages 14-23, ISSN 2319-4170,
- Randel A. H. pylori Infection: ACG Updates Treatment Recommendations. Am Fam Physician. 2018 Jan 15;97(2):135-137. PMID: 29365220.
- Dore, Maria Pina et al. “Dyspepsia: When and How to Test for Helicobacter pylori Infection.” Gastroenterology research and practice vol. 2016 (2016): 8463614. doi:10.1155/2016/8463614
- Romano, Marco, and Antonio Cuomo. “Eradication of Helicobacter pylori: a clinical update.” MedGenMed : Medscape general medicine vol. 6,1 19. 17 Feb. 2004
- PHE England Test and treat for Helicobacter pylori (HP) in dyspepsia
Quick reference guide for primary care: For consultation and local adaptation https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/828593/HP_Quick_Reference_Guide_v18.0_August_2019_change_highlighted.pdf
- Yoshio Yamaoka, “Pathogenesis of Helicobacter pylori-Related Gastroduodenal Diseases from Molecular Epidemiological Studies”, Gastroenterology Research and Practice, vol. 2012, Article ID 371503, 9 pages, 2012. https://doi.org/10.1155/2012/371503