Helicobacter pylori is a Gram-negative, spiral-shaped bacterium that has adapted to live in the acidic environment of the human stomach. H. pylori infections cause dyspepsia, peptic ulcer disease, and gastric adenocarcinoma. Additional disease associations include marginal zone B-cell lymphoma (MALToma), iron deficiency anemia, and idiopathic thrombocytopenic purpura (ITP). In North America, the prevalence of H. Pylori infections ranges between 30% and 40%.
The primary mode of transmission remains uncertain. Immediately following infection, H. pylori causes acute gastritis. Some individuals spontaneously clear H. pylori, but most develop persistent infection, which leads to chronic active gastritis. Subsequent complications include gastric and duodenal ulcers, gastric lymphoma, and gastric adenocarcinoma. An estimated 16% of infected individuals in the U.S. develop duodenal ulcers. Infection in early childhood increases risk for later development of gastric adenocarcinoma. Fewer than 5% of infected individuals develop gastric mucosa-associated lymphoid tissue lymphoma (MALToma).
H. pylori infection may be diagnosed by invasive (endoscopy) or noninvasive methods. Complications including GI bleeding, weight loss, older age, or persistence of symptoms after antimicrobial therapy are indications for endoscopy. From endoscopy, the organism may be identified by culture, immunohistochemical staining of a biopsy, or rapid urease testing (e.g. CLOtest).
Isolation of H. pylori by culture of a biopsy specimen provides definitive evidence of active infection. Sensitivity of culture is limited by poor viability during specimen transport and the special culture conditions that are required for bacterial growth.
Rapid urease tests are commonly used to detect H. pylori in biopsy specimens at the bedside. H. pylori produce urease, which is an enzyme that converts urea to ammonia and carbon dioxide. Biopsy specimen is submerged into a reagent containing urea. If H.pylori is present, ammonia is produced which increases the pH of the reagent and changes the color of the reagent. Sensitivity and specificity for active infection both exceed 90%. Sensitivity is decreased to approximately 75% in patients taking proton pump inhibitors, bismuth containing medications, or antibiotics.
Noninvasive testing includes serology, fecal antigen testing, and urea breath testing. Serological tests for IgG antibody to H. pylori are no longer recommended because of their poor positive predictive value and the persistence of antibodies after infection. Antibody testing cannot distinguish active from past infection and cannot be used to document eradication after therapy. Many major insurance companies no longer reimburse for H. pylori serologic testing. The American Gastroenterology Association and the American College of Gastroenterologists recommend either the urea breath test or the stool antigen test.
The noninvasive urea breath test (UBT) has excellent sensitivity and specificity (>93%) for the diagnosis of H. pylori infection when compared to invasive methods. This test has the same underlying principle as the rapid urea test. A patient drinks a solution containing C13 labeled urea, which is a nonradioactive isotope. If H. pylori is present, urease in the stomach converts urea to ammonia and C13 labeled carbon dioxide. The latter is exhaled into a special collection bag and analyzed by spectrophotometry. Increased amounts of labeled carbon dioxide, compared to a pre-ingestion specimen, indicate active infection.
UBT is useful in follow-up of patients after therapy. Providers should wait for at least 4 weeks following cessation of therapy to test for eradication of H. pylori. Like the rapid urease test, sensitivity and specificity are reduced by proton pump inhibitors, bismuth containing medications and antibiotics within 14 days of testing.
The stool antigen test is an enzyme immunoassay for detection of H. pylori antigen in stool specimens. Compared to other direct detection tests, the stool antigen test has a sensitivity of 93-98% with specificity of 88-96%. This test antigen is useful in confirming eradication after therapy. Antigen may be shed from nonviable organisms after treatment. Current guidelines recommend waiting 4 weeks following cessation of therapy before performing confirmatory testing. Use of antimicrobials, proton pump inhibitors, and bismuth preparations prior to testing may cause false negative results.
The stool antigen test requires a fresh stool specimen submitted in an airtight container and refrigerated prior to transport. Stool in transport media, swabs, or preservative is not appropriate. Results are reported as negative or positive. The reference value is negative.
Antimicrobial resistance to H. pylori has been increasing. Mutations in the 23S ribosomal RNA gene predict resistance to clarithromycin. DNA is purified from fecal samples and amplified by PCR. Amplified product is denatured and tested for mutations (A2143G and A2142G).
References
Chey WD, et al. ACG Clinical Guideline: Treatment of Helicobacter pylori Infection, Amer J Gastroenterologist, 2024;119:1730-53.
Malfertheiner P, Camargo MC, El-Omar E, et al. Helicobacter pylori infection. Nat Rev Dis Primers 2023;9(1):19.
Makristathis A, Hirschl AM, Megraud F, et al. Review: Diagnosis of Helicobacter pylori infection. Helicobacter 2019;24(Suppl 1):e12641.
Chen D, et al. Phenotypic and molecular antimicrobial susceptibility of Helicobacter pylori. Antimicrob Agents Chemother. 2017;61(4):e02530-16. doi:10.1128/AAC.02530-16
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