Helicobacter pylori (H. pylori), previously known as Campylobacter pylori, is one of the most common bacterial pathogens in humans. More than half of the world’s population and approximately 35% of the U.S. population are infected with H. pylori. Prevalence is highest in those with lower socioeconomic status, older age, and non-White ethnicity. Diagnostic testing for H. pylori can be either noninvasive (urea breath testing and stool antigen testing) or invasive (biopsy-based testing). For most patients with a low risk of gastric cancer, the test-and-treat strategy using noninvasive diagnostic testing is appropriate. In these cases, the decision to use a urea breath test versus a stool antigen test can be based on availability, cost, and acceptability, as both options are highly sensitive and specific for detecting persistent H. pylori infection. These same tests can also be used to evaluate the success of therapy.
Quick Answers for Clinicians
The urea breath test or the stool antigen test are the two noninvasive methods for the diagnosis of Helicobacter pylori (H. pylori) infection, and both are equally appropriate for adult patients younger than 60 years and without alarm symptoms. See Laboratory Testing.
Both tests have good positive and negative predictive value for diagnosing H. pylori infection. Neither test requires an endoscopy or biopsy specimen; however, stool collection or consumption of a urea-containing capsule or solution may be undesirable for some patients.
Serology is not recommended for the diagnosis of Helicobacter pylori (H. pylori) infection. - Serologic testing, whether for immunoglobulin G (IgG), IgM, or IgA, cannot accurately detect active infection because antibodies may remain long after successful treatment. Serology is also less sensitive and specific than either the urea breath test or the stool antigen test.
Indications for Testing
H. pylori testing is appropriate in patients who present with predominant epigastric pain lasting at least 1 month. The American College of Gastroenterology specifically recommends testing in individuals with active peptic ulcer disease (PUD), a history of PUD, or uninvestigated dyspepsia, and in those initiating prolonged treatment with a nonsteroidal anti-inflammatory drug (NSAID).
The decision to use noninvasive or invasive tests for the diagnosis of H. pylori infection depends on the age of the patient and whether the patient presents with alarm symptoms, which include gastrointestinal (GI) bleeding, unexplained iron deficiency anemia, early satiety, unexplained weight loss, progressive dysphagia, odynophagia, recurrent vomiting, family history of GI cancer, and previous esophagogastric malignancy. Noninvasive testing using either the urea breath test or the stool antigen test is indicated for adults younger than 60 years of age who present without alarm symptoms. Invasive testing methods that involve endoscopy and biopsy are indicated for children, adults 60 years and older, and those with alarm symptoms. However, noninvasive testing may be acceptable for children when a false-negative invasive test result is suspected or when evaluating causes of chronic immune thrombocytopenic purpura.
For accurate results, it is recommended that patients stop use of proton-pump inhibitors (PPIs) for 2 weeks before any H. pylori testing. Histamine 2-receptor antagonists may reduce urease activity on urea breath tests and should be discontinued 24-48 hours before sample collection.
Urea Breath Test
The 13C-urea breath test is the most commonly utilized noninvasive approach for the diagnosis of active H. pylori infection. Testing requires the patient to fast and abstain from smoking for 1 hour before testing. Achlorhydria or urease-positive organisms other than H. pylori in the gut may increase the risk of a false-positive result.
Invasive testing strategies require upper endoscopy with biopsy. Biopsy of the antrum is recommended at a minimum, but biopsy of additional areas (eg, the corpus) may improve diagnostic utility and is recommended in children. Biopsy-based tests are less sensitive when performed in patients with active GI bleeding; if a false-negative result is suspected, noninvasive testing can be considered.
The rapid urease test is recommended as a first-line diagnostic test when endoscopy is indicated and there is no contraindication for biopsy. This test is accurate, inexpensive, highly sensitive, and enables treatment to begin immediately. However, the rapid urease test is not always specific for H. pylori because other urease-positive organisms in the gut may cause a false-positive result. In addition, the sensitivity of urease-based tests is decreased in patients with active GI bleeding; therefore, histology may be preferred in these patients.
Histology (With or Without Staining)
The sensitivity of histology in detecting H. pylori is subject to the area being sampled and the number of samples, but the addition of stains (eg, Giemsa, Warthin-Starry, hematoxylin and eosin, or immunohistochemistry) may increase the sensitivity. Histologic evaluation has the added value of potentially uncovering an unsuspected pathology, such as inflammation, metaplasia, dysplasia, and malignant neoplasm. Although PPIs and antibiotics can interfere with bacterial density, histology is better for patients who have recently used these medications. In children, histology should be performed in addition to another biopsy-based test.
Although culture has a specificity of 100%, it is less sensitive than either the rapid urease test or histology and has the disadvantage of requiring a 2-week incubation period that may or may not yield successfully growing colonies. However, it is recommended in children and can be used as the sole test for diagnosis in this patient group. An additional benefit of culture is that it enables antibiotic susceptibility testing.
Follow-up testing after treatment using either the urea breath test or stool antigen test is recommended in both children and adults. This testing should occur no sooner than 4 weeks after completion of antibiotic therapy and after PPI therapy has been suspended for 1-2 weeks. Biopsy-based testing can also be performed in adults when a repeat endoscopy is needed. Because all tests are highly sensitive and specific, the choice of which test to use can be based on patient needs and preferences. However, the rapid urease test is not recommended by some to evaluate whether H. pylori has been eradicated by treatment.
ARUP Laboratory Tests
Use to diagnose H. pylori infection in adults
Use to confirm eradication of H. pylori at least 4 weeks after completion of therapy
Do not order for children <18 years
Use to confirm eradication of H. pylori in patients 3-17 years of age who are diagnosed by endoscopy and appropriately treated
Aliases: 13C-urea breath test, urea breath test
Use to diagnose H. pylori infection (an alternative to the urea breath test)
Use to confirm eradication of H. pylori at least 4 weeks after completion of therapy
Less accurate in pediatric patients
Aids in histologic diagnosis of H. pylori
Stained and returned to client pathologist; consultation available if needed
Consider for diagnosis of H. pylori infection in children or for susceptibility testing in patients with treatment failure
Cultures positive for H. pylori will be sent for susceptibility testing to Mayo Medical Lab
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Clinical Microbiology Newsletter - Non-Helicobacter pylori Helicobacter Species Associated with Human Disease: a Primer for the Clinical Microbiology Laboratory
Powers-Fletcher MV, Couturier MR. Non-Helicobacter pylori Helicobacter species associated with human disease: a primer for the clinical microbiology laboratory. Clinical Microbiology Newsletter. [Published: Jun 2015; Accessed: May 2020]