What is Helicobacter Pylori?
• Bacteria in the gut that convert urea into ammonia to survive the harsh acidic conditions in the stomach (1).
• It's a spiral bacterium that lives on the stomach lining. High mobility and ability to produce ammonia allows it to survive in the highly acidic conditions of the stomach.
• Shape: 2-4 micrometers in length and 0.5-1 micrometers in width but carries 2-6 rod-like flagella that are about 3 micrometers in length, with a distinctive bulb at the head.
• Several species of Helicobacter exist; however, Helicobacter pylori is specific to the human stomach. Different Helicobacter species have also been found in cats, dogs and other animals where they are known to cause ulcers.
• H. pylori strongly adapts to our unique stomach environments allowing it to stay throughout our lives—one reason why infections acquired during childhood continue in adults.
• The pH of stomach lining varies between 4 and 6.5 and the bacterium prefers to grow around a pH of 5.5; it survives the fluctuations in stomach acidity by converting urea in the stomach into ammonia and bicarbonates, and by quickly moving away from high acidic regions—this unique ability to digest urea is a hallmark of H. pylori, and is frequently used for confirming the infection.
How prevalent is H. pylori?
Prevalence (approximate data from 2013-14) (2):
- US and Canada: 30-35%
- Mexica: 50%
- Western Europe: 30-70%
- Eastern Europe: 40-80%
- India and China: 60%
- Turkey: 80%
- Ethiopia: 65%
Prevalence in younger generation is lower, e.g., in China the numbers were 30% in children compared to almost 60% in adults (2).
For past several decades, there is a steady decline in cases due to better hygiene & other unknown reasons. As an example, in The Netherlands, cases declined from 48% in 1940s to 16% in 1980s (2).
In developing countries, the infections often start in children and continue as they grow into adults, causing acidity, ulcers and stomach cancers. However, in developed countries most cases are observed among adults. First and second-generation immigrants from developing countries have higher rates compared to natives, likely from infections acquired during childhood.
Transmission of H. pylori:
- How H. pylori transmits is not completely understood; however, with high probability, children acquire it during early childhood.
- Most likely medium of transmission among people is either oral through saliva or fecal or both.
- The bacterium has been detected in saliva, vomit, gastric reflux and feces.
- There are no data to support infection from dentists, nurses, clinic visits for sexually-transmitted-disease or gastroenterologists (3).
What are the risk factors and who is at risk of H. pylori infection?
- Family members: 75% of spouses and parents of children and half of siblings have been found to be in positive for those infected (4).
- Age: About one-third of children and adults under 30 years of age have been found infected but the numbers increase to almost two-third among the 55-65 age groups (5).
- Race: Risk of infection among African Americans and Hispanic groups is twice that among Europeans (6).
- Living conditions: Risk increases among those sharing beds and living in crowded homes, as close proximity increases the oral or fecal transmission of the bacteria; those in rural communities seem to have higher prevalence than in urban communities (7).
- Others: Risk has been found to be higher in US for those in lower socio-economic backgrounds, poor living conditions, recently immigrated from regions with higher prevalence (e.g., developing or tropical countries).
- No difference was found between genders. The impact of smoking and alcohol is also not clearly understood (7).
- There might be some genetic component that is not yet fully understood, because studies of identical twins growing apart still often show similar infections (8).
Risk increases with additional symptoms of:
- Weight loss
- Gastrointestinal bleeding
- Difficult in swallowing (dysphagia)
- Family history of abnormal and excessive tissue growth (neoplasm)
- Indigestion (dyspepsia)
What are the implications of infection?
- Helicobacter pylori is a known carcinogen (9); although extremely rare, yet studies have shown that it can cause cancer of the duodenum (end of stomach connects to the small intestine ).
- Infections are often asymptotic but in serious cases, they can cause high acidity, ulcers, and acid reflex which can be very difficult to diagnose.
- Infection generally has no immediate implications unless it results in clinical symptoms such as ulcers or other annoying side effects.
- There are no clear data to indicate H. pylori increases the risk of GERD or heart burn (1).
- The risk of developing gastric cancer due to H. pylori in US and Europe is relatively small (1-2% cases), though the bacterium infection increases the risk 10-fold and treatment seem to have no change in this risk (1).
What are the various testing methods for H. pylori? (10):
- Urea breath test: when the bacteria convert carbon-labeled urea into ammonia & CO2 which can be detected through breath test (about 95% sensitivity and specificity—true positive and true negative rates); the cost is much higher at 4-5 times of fecal antigen test.
- Fecal antigen test: an ELISA test that checks for the presence of bacteria in stool (about 95% sensitivity and specificity).
- Blood antibody test: checks for IgG antibodies in the blood from current or past infections; does not depend on medication or antibiotics; and the test is an efficient way to check for large groups and population-based studies.
H. pylori antibody test: Advantages, Limitations and Things to Keep in Mind
- Advantage: Simple and easy test with a finger prick sample that can be collected at home and mailed to the lab without leaving home; does not depend on medication (e.g., PPIs) or antibiotics.
- Limitation: can't tell whether it's currently active or a past infection, therefore a positive case might require another stool or urea breath test for confirmation.
Things to Keep in Mind:
- An IgG antibody test checks for immune response against the infection--very recent infections might not have produced enough antibodies to detect or very old infections might also have very little antibodies left in the body; and some people may not produce enough antibodies.
- For taking the stool test, one should not be on acid reducing medications (PPIs or proton-pump inhibitors such as Nexium, Prilosec, Omeprazole, Esomeprazole, Protonix) for at least two weeks and should not be on antibiotics for at least 4 weeks; the blood antibody test has no such requirement.
What’s the treatment for H. pylori infection?
- A triple therapy of PPI (Omeprazole, Esomeprazole, Nexium or Prilosec) and antibiotics (amoxycillin and levofloxacin or clarithromycin or bismuth-containing quadruple regimen) for 7-14 days is a prescribed testing methodology (11).
- Probiotics have shown to help with better outcomes in treatment (12).
- Mayo Clinic’s clinician recommendation suggests all treatment regimens should be taken for 14 days, and eradication testing should be performed in all patients (13).
What are the known virulence factors for H. pylori?
Definition: Just as our body develops immunity against bacteria and viruses over time, these pathogens have clever defense mechanisms to counteract and overcome our body's defense mechanisms. They carry 'virulence' genes that are capable of producing molecules that allow them to enter the body, hide without detection, and then multiply and grow to cause infections (14). In that sense, 'virulence factors' are genes that allow the bacterial 'wolfs' to wrap themselves in the 'sheep's clothing' of our body's cells (15).
Some of these protein molecules are more dangerous than others. For H. pylori, certain strains or variations of the bacteria are more infectious. Few of them are listed here (1):
- cagA: this gene produces a protein CagA (also called cytotoxin-associated gene A) and is found more often than others—about 50-70% of all strains in US and Europe; its presence causes more severe infection, stronger gastritis (acidity), higher inflammation and greater risk of ulcer disease and gastric cancer.
- vacA: vacuolating toxin A—which causes holes-like features in the cells—about half of strains carry vacA; this gene increases the risk of damage to the stomach lining and vacA carrying strains also have much higher adaptability, which allows a more persistent infection observed as a constant growing and shrinking ulcer.
- babA: blood-group antigen binding adhesion, known to increase the risk of peptic ulcer and gastric cancer, and often a more severe disease and long-term infection.
- dupA: duodenal-ulcer promoting gene A, is associated with ulcer in the duodenum (the part of stomach connecting with small intestine), but it is known for reduced risk of damage to the stomach lining.
- iceA: induced-by-contact-with-epithelium A, a gene causing higher inflammation and, in some instances, even causing peptic ulcer.
- oipA: outer-membrane inflammatory protein A gene, is often linked to cagA and is known to cause duodenal ulcer and gastric cancer.
- virB and virD are part of the cagA pathogenicity island (PAI—the gene clusters of pathogens responsible for causing the disease) & increase the risk of peptic ulcer and gastric cancer.
Source: The Nobel Prize: https://www.nobelprize.org/prizes/medicine/2005/press-release/
- Johannes G. Kusters, Arnoud H. M. van Vliet, and Ernst J. Kuipers, The Pathogenesis of Helicobacter pylori Infection, Clin Microbiol Rev. 2006 Jul; 19(3): 449–490.
- Dulciene Maria Magalhães Queiroz Francesco Luzza, Epidemiology of Helicobacter pylori Infection, Helicobacter, Vol 11 (1), Oct 2006.
- F. Mégraud, Transmission of Helicobacter pylori: faecal-oral versus oral-oral route, Aliment Pharmacol Ther. 1995;9 Suppl 2:85-91.
- Yavuz Selim Sari et. al., H pylori: Treatment for the patient only or the whole family? World J Gastroenterol. 2008 Feb 28; 14(8): 1244–1247.
- P. M. Webb et. al., Relation between infection with Helicobacter pylori and living conditions in childhood: evidence for person to person transmission in early life, BMJ, 1994 Mar 19; 308(6931):750-3.
- James E. Everhart et. al., Seroprevalence and Ethnic Differences in Helicobacter pylori Infection among Adults in the United States, The Journal of Infectious Diseases, Volume 181, Issue 4, April 2000, Pages 1359–1363.
- Leonardo H. Eusebi, Rocco M. Zagari and Franco Bazzoli, Epidemiology of Helicobacter pylori Infection, Helicobacter 19 (Suppl. 1): 1–5.
- H. M. Malaty, L. Engstrand, N. L. Pedersen, and D. Y. Graham, Helicobacter pylori infection: genetic and environmental influences. A study of twins, Ann Intern Med 94 Jun 15;120(12):982-6.
- The Nobel Prize: https://www.nobelprize.org/prizes/medicine/2005/press-release/.
- Chiara Ricci, John Holton, and Dino Vaira, Diagnosis of Helicobacter pylori: invasive and non-invasive tests, Best Pract Res Clin Gastroenterol. 2007; 21(2):299-313.
- William D Chey, Benjamin C Y Wong, American College of Gastroenterology guideline on the management of Helicobacter pylori infection, Am J Gastroenterol. 2007 Aug;102(8):1808-25.
- Goran Hauser, Nermin Salkic, Karina Vukelic, Alenka JajacKnez, Davor Stimac, Probiotics for standard triple Helicobacter pylori eradication: a randomized, double-blind, placebo-controlled trial, Randomized Controlled Trial, Medicine (Baltimore) 2015 May; 94(17):e685.
- Amrit K. Kamboj, Thomas G. Cotter, and Amy S. Oxentenko, Helicobacter pylori: The Past, Present, and Future in Management, Mayo Clin Proc. April 2017; 92(4):599-604.
- Steven AR Webb and Charlene M Kahler, Bench-to-bedside review: Bacterial virulence and subversion of host defences, Critical Care, Volume 12, Article number: 234 (2008).
- Alan S Cross, What is a virulence factor? Crit Care. 2008; 12(6): 196.