H. pylori Serology vs. Stool/Antigen Tests: Key Differences
Serology tests detect antibodies from past or present H. pylori exposure and cannot distinguish between active infection and previous exposure, making them unsuitable for diagnosing active infection or confirming eradication, whereas stool antigen tests detect active bacterial presence and are the preferred non-invasive diagnostic method alongside urea breath tests. 1
Critical Distinction: Active Infection vs. Past Exposure
Serology (Blood Antibody Tests)
- Detects anti-H. pylori IgG antibodies in serum but cannot differentiate between current active infection and previous exposure 1
- Antibody levels persist in blood for months to years after H. pylori elimination, leading to false-positive results in previously treated patients 1, 2
- Overall accuracy of commercial ELISA serology tests averages only 78% (range 68-82%), which is inadequate for clinical use 1
- The positive predictive value falls dramatically in populations with low disease prevalence 1
Stool Antigen Tests
- Directly detect H. pylori bacterial antigens in stool specimens with sensitivity and specificity of approximately 93%, comparable to urea breath testing 1
- Detect active infection only, not past exposure 1
- Valuable for both initial diagnosis and confirmation of eradication 1
- Laboratory-based validated monoclonal antibody tests achieve high accuracy—rapid in-office immunochromatographic tests have significantly lower accuracy and should be avoided 1
Clinical Applications and Limitations
When Serology Should NOT Be Used
- Never use serology to confirm eradication after treatment as antibodies remain elevated after H. pylori elimination 1, 2
- Not recommended as the primary diagnostic method for H. pylori infection 1
- Rapid in-office serological tests have limited accuracy (sensitivity 63-97%, specificity 68-92%) and should be avoided 3, 1
Limited Situations Where Serology May Be Appropriate
- When patients have recently used antibiotics, bismuth products, or proton pump inhibitors (PPIs) that could cause false-negative results with other tests 1
- In patients with gastric atrophy, gastric malignancies, or ulcer bleeding where bacterial load may be low 1
- Large epidemiologic surveys and population screening in high-prevalence areas 3
- When clinical suspicion is high but other tests might be falsely negative 1
Preferred Testing Strategy
- For initial diagnosis: Use urea breath test (UBT) with sensitivity 94.7-97% and specificity 95-95.7%, or laboratory-based monoclonal stool antigen test with sensitivity and specificity >90% 1, 4
- For confirmation of eradication: Use UBT or stool antigen test at least 4 weeks after completing treatment 1, 4
- Both tests require proper medication washout: stop PPIs for at least 2 weeks and antibiotics/bismuth for at least 4 weeks before testing 1, 4
Common Pitfalls to Avoid
- Do not use serology for post-treatment evaluation within 6-12 months of therapy 2
- Avoid testing panels of IgG, IgA, and IgM as they provide no added benefit over validated IgG tests 1
- Failure to stop PPIs before testing leads to false-negative results in all tests except serology 1
- Testing before 4 weeks post-treatment yields unreliable results due to temporary bacterial suppression 4
Algorithm for Test Selection
For patients under 50 years without alarm symptoms (bleeding, weight loss, dysphagia):
- First choice: 13C-urea breath test or laboratory-based monoclonal stool antigen test 1
- If recent antibiotic or PPI use: Consider validated IgG serology OR wait 2-4 weeks after stopping medications 1
For patients requiring endoscopy (alarm symptoms, age ≥50, treatment failure):
- Perform rapid urease test, histology, or culture during endoscopy 1
- Consider culture and antimicrobial sensitivity testing after treatment failure 1, 5
For confirmation of eradication: