What is the best method to test for Helicobacter (H.) pylori infection in an adult patient with epigastric pain and no known medical history?

Testing for H. pylori Infection

For adults with epigastric pain and no alarm symptoms, use the urea breath test (UBT) or laboratory-based monoclonal stool antigen test as your first-line diagnostic method—these non-invasive tests have excellent accuracy (sensitivity 93-97%, specificity 93-95%) and avoid unnecessary endoscopy. 1, 2

Initial Diagnostic Strategy Based on Patient Age and Symptoms

Patients Under 50-55 Years Without Alarm Symptoms

• Start with non-invasive testing using either UBT or stool antigen test rather than proceeding directly to endoscopy 1, 3
• This "test and treat" strategy reduces unnecessary endoscopies by 62% while maintaining equivalent safety and symptom outcomes 1
• Both tests detect active infection (not just past exposure), making them reliable for initial diagnosis 1, 2

Patients Requiring Endoscopy (Proceed Directly to Invasive Testing)

• Age ≥50-55 years with new-onset dyspepsia due to increased gastric cancer risk 1
• Any patient with alarm symptoms regardless of age: bleeding, weight loss, dysphagia, palpable mass, anemia, or malabsorption 1
• Patients who failed previous eradication therapy when culture and antimicrobial susceptibility testing are needed 1

Non-Invasive Testing Methods

Urea Breath Test (UBT)

• Most accurate non-invasive test with sensitivity of 94-97% and specificity of 95-97.7% 1, 2
• Detects active H. pylori by measuring urease enzyme activity 2
• Requires 6-hour fasting before the test for optimal accuracy 2
• Use 13C-labeled urea (not 14C) in children and pregnant women to avoid radiation exposure 1

Stool Antigen Test

• Laboratory-based monoclonal antibody test achieves sensitivity and specificity of approximately 93%, comparable to UBT 1, 2
• Directly detects H. pylori bacterial antigens in stool specimens 1
• Avoid rapid in-office immunochromatographic stool tests—these have significantly lower accuracy (80-81%) and should not be used 2
• Excellent alternative when UBT is unavailable or for post-treatment confirmation 2

Serology Testing (Limited Role)

• Do NOT use serology for routine diagnosis—overall accuracy averages only 78% (range 68-82%) 1, 2
• Cannot distinguish between active infection and past exposure; antibodies persist for months to years after eradication 1, 2
• Never use serology to confirm eradication after treatment 1, 2
• Consider serology only when: patient recently used PPIs or antibiotics and medication washout is not possible, ulcer bleeding present, gastric atrophy/malignancy suspected 1, 2

Invasive Testing During Endoscopy

Rapid Urease Test (RUT)

• Sensitivity 80-95%, specificity 95-100% before treatment 2
• Provides quick results during endoscopy procedure 1
• Requires approximately 10,000 organisms for positive result 2

Histology

• Gold standard among invasive tests when using immunohistochemistry 2
• Requires at least 2 biopsy samples from both antrum and body for improved sensitivity 1, 2
• Follow the 5-biopsy Sydney System: specimens from lesser and greater curve of antrum (within 2-3 cm of pylorus), lesser curvature of corpus (4 cm proximal to angularis), middle portion of greater curvature of corpus (8 cm from cardia), and incisura angularis 4
• Place all specimens in the same jar 4
• Do not obtain automatic special staining—experienced pathologists can identify H. pylori on routine H&E stains in most cases; reserve immunohistochemistry for equivocal results 4

Culture with Susceptibility Testing

• Provides definitive proof and antimicrobial resistance patterns 1, 2
• Particularly valuable in regions with high clarithromycin resistance (>15-20%) or after treatment failure 1
• Technically demanding with variable sensitivity between laboratories 2

Critical Medication Washout Periods to Avoid False-Negative Results

These washout periods apply to all tests EXCEPT serology:

• Stop proton pump inhibitors (PPIs) for at least 2 weeks before testing—PPIs cause 10-40% false-negative rates by reducing bacterial load 1, 2
• Stop antibiotics and bismuth compounds for at least 4 weeks before testing 1, 2
• Histamine-2 receptor antagonists do not affect bacterial load and can substitute for PPIs when acid suppression is needed before testing 1

Post-Treatment Confirmation of Eradication

• Test at least 4 weeks after completing eradication therapy 1, 2
• Use UBT or laboratory-based monoclonal stool antigen test only—never use serology 1, 2
• Confirmation is strongly recommended in: complicated peptic ulcer disease, gastric ulcer, gastric MALT lymphoma 1
• Stool antigen test for post-treatment confirmation has sensitivity 91.6% and specificity 98.4% 1

Common Pitfalls to Avoid

• Do not use rapid in-office serological tests or immunochromatographic stool tests—accuracy is inadequate for clinical use 1, 2
• Do not test patients currently taking PPIs, antibiotics, or bismuth without appropriate washout periods (except when using serology) 1, 2
• Do not use panels of IgG, IgA, and IgM tests—these provide no added benefit over validated IgG tests and may include non-FDA-approved tests 1
• Do not rely on serology alone for diagnosis in routine clinical practice—it cannot confirm active infection 1, 2