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.
Mnemonic: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.
References for H. pylori: