Serology-IgG or IgA antibodies directed at various bacterial antigens can be detected by enzyme-linked immunosorbent assay (ELISA) in serum of infected individuals. In addition, several office-based serologic methods are commercially available. Serologic methods detect evidence of primary H. pylori infection in untreated people with sensitivity and specificity >90%. Although antibody levels may fall after successful bacterial eradication, they remain elevated for up to 3 years. This “serologic scar” limits the usefulness of serology in assessing treatment and determining reinfection as well as reduces the positive predictive value of the test, especially in areas of the world (such as the United States) where prevalence of infection is low. For this reason a positive serology result should be confirmed with a test of active infection, such as a stool or urea breath test before treatment is initiated.

Urea breath or blood tests are ideally suited to make a primary diagnosis of infection, to monitor treatment response, and to assess reinfection, because they are positive only in a setting of active infection. The patient ingests a small amount of carbon-labeled (13C or 14C) urea. The urease of H. pylori hydrolyzes the urea and liberates labeled carbon dioxide, which is absorbed and exhaled in the breath. Labeled carbon dioxide can be collected and quantified in breath or blood samples. Sensitivity and specificity of urea breath or blood testing are >95%. Certain medications can influence test results.

Stool antigen testing is becoming increasingly popular. It is accurate (sensitivity and specificity = 90% and 98%, respectively) and inexpensive. The test is based on polymerase chain reaction amplification of specific H. pylori antigens in stool samples. Stool antigen testing is useful in primary diagnosis and confirmation of eradication of the organism after antibiotic treatment. Certain medications can influence test results

Reference:
Vaira D, Gatta L, Ricci C, Miglioli M: Review article: Diagnosis of Helicobacter pylori infection. Aliment Pharmacol Ther 16(Suppl 1):16-23, 2002.

Histopathologic examination is widely available, and specimens are easy to store. Organisms can be detected with standard hematoxylin and eosin stains or special stains, such as Giemsa or Warthin-Starry, which make the organisms easier to identify. The sensitivity and specificity of histopathology for H. pylori are greater than 95% but may be influenced by sampling error, number of organisms present, use of proton pump inhibitors, and experience of the pathologist.
Rapid urease testing relies on the potent urease activity of H. pylori, when a gastric biopsy specimen is placed in medium containing urea and a colored pH indicator. If the organism is present in the specimen, its urease hydrolyzes urea to bicarbonate and ammonia, increasing the pH and changing the color of the pH indicator. The number of organisms present, use of certain medications, and sampling error may influence urease testing. The sensitivity of the rapid urease test is approximately 90%; its specificity is 100%.

Reference:
Vaira D, Gatta L, Ricci C, Miglioli M: Review article: Diagnosis of Helicobacter pylori infection. Aliment Pharmacol Ther 16(Suppl 1):16-23, 2002.

The organism generally does not directly invade the epithelial cells but indirectly makes the gastric mucosa more vulnerable to acid peptic damage by disrupting the mucous layer, liberating a variety of enzymes and toxins, and adhering to and altering the gastric epithelium. In addition, the host immune response to H. pylori incites an inflammatory reaction that further perpetuates tissue injury. This chronic inflammation upsets gastric acid secretory physiology to varying degrees and leads to chronic gastritis, which, in most individuals, is asymptomatic but, in some, will lead to ulcers and even gastric cancer.

Reference:

• McColl L, El-Omar E, Gillen D: Helicobacter pylori gastritis and gastric physiology. Gastroenterol Clin North Am 29:687-703, 2000.

The organism lives within or beneath the gastric mucous layer, somewhat protected from stomach acid. H. pylori has potent urease activity, which hydrolyzes urea to ammonia and bicarbonate and increases its resistance to the stomach’s low pH environment. H. pylori recognizes and binds to specific receptors expressed by gastric epithelial cells and, therefore, is able to adhere tightly to the epithelial cell surface. This attachment process may morphologically or functionally alter the epithelial cell. The organism has been found adherent to ectopic gastric epithelium throughout the GI tract, that is, esophagus (Barrett’s), duodenum (gastric metaplasia), small intestine (Meckel’s diverticulum), and rectum (ectopic patches of gastric mucosa).

Reference:

• McColl L, El-Omar E, Gillen D: Helicobacter pylori gastritis and gastric physiology. Gastroenterol Clin North Am 29:687-703, 2000.

H. pylori is a spiral-shaped, gram-negative bacterium, 0.5 microns in width and 2-6.5 microns in length. It is distinguished by its multiple sheathed, unipolar flagella and potent urease activity; urease accounts for more than 1% of the organism’s protein weight. Its shape and flagella allow penetration of and movement through the gastric mucus layer while its urease activity appears essential for colonization and survival. H. pylori is unique in its ability to survive within the hostile acid environment of the stomach. Although gastric bacteria were described as early as the turn of the 20th century, their importance in peptic ulcer disease and chronic gastritis was not appreciated until the 1980s. H. pylori was first successfully cultured in 1982 by Marshall and Warren.

Reference:

• Marshall BJ, Warren JR: Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration. Lancet 1:1311-1315, 1984.

Patients chronically infected with H. pylori frequently develop gastric and duodenal ulcer disease, especially the latter. Although less common, B-cell lymphoma and adenocarcinoma of the stomach are also associated with chronic gastritis due to H. pylori. Antral-predominant corpus sparing chronic gastritis due to H. pylori is more often associated with duodenal ulcer. Gastritis involving the entire stomach with intestinal metaplasia and achlorhydria is associated with gastric ulcer and cancer. B-cell lymphoma is often seen in conjunction with H. pylori infection and very often resolves with eradication of the bacteria.

Reference:
Graham DY: H. pylori infection in the pathogenesis of duodenal ulcer and gastric cancer: A model. Gastroenterology 113:1983-1991, 1997.

Lymphocytic gastritis (LG) is a special form of gastritis, which is characterized by the accumulation of intraepithelial lymphocytes (IELs) containing cytotoxic granules in the surface and foveolar epithelium. The number of IELs in normal gastric mucosa is between 3 and 8 per 100 epithelial cells; a minimal number of 30 IELs per 100 epithelial cells is usually accepted for the diagnosis of LG. LG is usually asymptomatic. Patients occasionally present with epigastric pain or anorexia. It often occurs in association with H. pylori infection and celiac disease. However, only 2-4% of patients with H. pylori infection will develop LG. There is no specific therapy for LG. However, patients who are serologically positive for H. pylori, but negative by all other diagnostic techniques, may still respond to antimicrobial therapy for that organism.

Reference:

• Hayat M, Arora DS, Dixon MF: Effects of Helicobacter pylori eradication on the natural history of lymphocytic gastritis. Gut 45(4):495-498, 1999.
• Oberhuber G, Bodingbauer M, Mosberger I: High proportion of granzyme B-positive (activated) intraepithelial and lamina propria lymphocytes in lymphocytic gastritis. Am J Surg Pathol 22(4):450-458, 1998.