A 48-year-old man with a 2-month history of epigastric pain and early satiety undergoes upper endoscopy, which reveals gastric antral erythema and a small ulcer. Multiple gastric biopsies are taken. Which investigation is the most sensitive and specific for diagnosing *Helicobacter pylori* infection in this patient?

## Diagnosis of *Helicobacter pylori* Infection **Key Point:** The rapid urease test (CLO test) on fresh gastric biopsy is the gold-standard *in situ* diagnostic method for H. pylori, with sensitivity and specificity both >95% when performed immediately. ### Why Rapid Urease Test (CLO Test)? *Helicobacter pylori* produces abundant urease, which cleaves urea to ammonia and CO~2~, raising local pH. The CLO (Campylobacter-like organism) test detects this enzymatic activity within 1–2 hours: - **Sensitivity:** 95–98% (highest among biopsy-based tests) - **Specificity:** 95–100% - **Advantage:** Direct detection of organism in the gastric mucosa - **Timing:** Immediate result available during endoscopy ### Diagnostic Algorithm for H. pylori ```mermaid flowchart TD A[Suspected H. pylori<br/>Gastric symptoms]:::outcome --> B{Endoscopy<br/>indicated?}:::decision B -->|Yes| C[Obtain gastric biopsies]:::action C --> D[Rapid urease test<br/>CLO test]:::action D -->|Positive| E[H. pylori confirmed]:::outcome D -->|Negative| F{High clinical<br/>suspicion?}:::decision F -->|Yes| G[Histology + Culture]:::action F -->|No| H[Consider serology<br/>or UBT]:::action B -->|No| I[Urea breath test<br/>or serology]:::action ``` ### Comparison of H. pylori Diagnostic Tests | Test | Sensitivity | Specificity | Timing | Requires Endoscopy | Best Use | |------|-------------|-------------|--------|-------------------|----------| | **Rapid urease (CLO)** | 95–98% | 95–100% | 1–2 hrs | Yes | Gold standard for biopsy | | Histology + culture | 90–95% | 100% | 2–4 weeks | Yes | Confirmatory; culture for resistance | | Serum IgG ELISA | 85–90% | 85–90% | Same day | No | Screening; cannot distinguish active from past infection | | Urea breath test (^13^C-UBT) | 95–98% | 95–98% | 30 min | No | Non-invasive; preferred for follow-up | | Stool antigen (ELISA) | 90–95% | 90–95% | Same day | No | Non-invasive; less sensitive than UBT | **High-Yield:** In a patient undergoing endoscopy with gastric biopsies already obtained, the rapid urease test is the fastest and most practical confirmatory test. **Warning:** Serum IgG antibodies persist for years after successful eradication — cannot be used to assess treatment success. Urea breath test is preferred for post-treatment confirmation. ### Clinical Pearl *Helicobacter pylori* is the leading cause of peptic ulcer disease in India. The rapid urease test is cost-effective and widely available in endoscopy units, making it the investigation of choice when biopsies are already being taken. [cite:Harrison 21e Ch 297; Park 26e Ch 3]