Skip to content
Download PDF

Helicobacter pylori Infections

Part 5: Infectious Diseases | Part 5 – Infectious Diseases: Bacterial · Part 5 – Infectious Diseases: Bacterial · Chapter 168

Key Clinical Points

  1. H. pylori is a gram-negative bacillus that has naturally colonized humans for at least 100,000 years.
  2. Colonization with H. pylori is the main risk factor for peptic ulceration and gastric adenocarcinoma.
  3. Antral-predominant gastritis is linked to duodenal ulceration; corpus-predominant gastritis is linked to gastric ulceration and adenocarcinoma.
  4. Carriage of cag-positive strains increases the risk of both peptic ulcer and gastric adenocarcinoma.
  5. H. pylori eradication is first-line therapy for low-grade gastric MALT lymphoma.
  6. Alarm symptoms (e.g., weight loss) require upper gastrointestinal endoscopy to exclude malignancy.
  7. Testing for H. pylori must be performed after a washout period: 2 weeks off PPIs, 4 weeks off antibiotics/bismuth.
  8. First-line treatment consists of a PPI and two or three antimicrobial agents given for 10–14 days.
  9. H. pylori eradication leads to symptom resolution in functional dyspepsia up to 15% more commonly than placebo.
  10. H. pylori colonization may offer protection against complications of gastroesophageal reflux disease (GERD), although this is uncertain.

1. DEFINITION & OVERVIEW

• Microbiology: Gram-mediated bacillus; colonized humans for ≥ 100,000 years. • Habitat: Gastric mucus; portion adheres to mucosa and may enter cells. • Motility: Spiral shape and flagella enable movement in mucus. • Acid Resistance: Urease production → generates buffering ammonia. • Growth Characteristics: Microaerophilic, slow-growing; requires complex media in vitro. • Prevalence: Colonizes ~40% of the global population; persists for life unless eradicated. • Clinical Significance: Major risk factor for peptic ulceration, gastric adenocarcinoma, and MALT lymphoma. • GERD Interaction: Potential protection against GERD complications via hypochlorhydria (uncertain).

1.1 Other Helicobacter Species

• Non-H. pylori species: Small proportion of gastric infections; potentially zoonotic. • Clinical Impact: Associated with low-level inflammation and occasional disease. • Immunocompromised Hosts: Intestinal Helicobacter species may cause Campylobacter-like infections.

2. EPIDEMIOLOGY

• Global Prevalence: 60% in Africa, South America, and West Asia. • US Prevalence: ~18% of adults; 14% of children/adolescents. • Acquisition: Primarily in childhood; linked to crowding and social deprivation. • Transmission: Human is the sole reservoir; likely oral–oral or fecal–oral routes.

2.1 Host Determinants of Disease

• Genetic Factors: Polymorphisms in cytokine genes (e.g., IL-1) and Toll-like receptors → increased gastric cancer risk. • Environmental Factors: → Smoking: Increases duodenal ulcer/gastric cancer risk. → High-salt diets: Increase cancer risk. → Antioxidant-rich diets: Protective.

3. ETIOLOGY & PATHOPHYSIOLOGY

• Host Response: Long-term colonization causes chronic superficial gastritis with immune infiltration; immune downregulation prevents clearance.

3.1 Bacterial Virulence Factors

• cag-positive strains: Increase ulcer/gastric cancer risk via CagA translocation and VacA pore formation. • Adhesins: BabA binds to epithelial cell antigens; other components recognized by Nod1.

3.2 Pathogenesis of Duodenal Ulceration

• Mechanism: H. pylori-induced antral gastritis → reduced somatostatin-producing D cells → increased gastrin levels → increased acid secretion from the corpus. • Consequence: Promotes duodenal metaplasia and ulceration.

3.3 Pathogenesis of Gastric Ulceration and Gastric Adenocarcinoma

• Corpus-predominant gastritis: Leads to hypochlorhydria despite hypergastrinemia. • Gastric Ulcers: Occur at antral-corpus junctions. • Adenocarcinoma: Arises in atrophic gastritis; DNA damage caused by inflammatory ROS/NOS.

3.4 Pathogenesis of Gastric MALT Lymphoma

• Mechanism: Chronic colonization stimulates lymphocytes → low-grade B-cell MALT lymphoma. • Genetics: CagA-positive strains associated with t(11;18) translocations. • Prognosis: Eradication may induce regression in ~70% of cases.

4. CLINICAL FEATURES

• Prevalence of Disease: Histologic gastritis in all infected; only 10–15% develop ulcers, cancer, or lymphoma. • Gender Difference: Women have lower disease rates than men. • Functional Dyspepsia: Eradication → symptom resolution (15% more common than placebo). • GERD/Esophageal Cancer: Inverse association with H. pylori prevalence; likely due to hypochlorhydrian-mediated protection.

4.1 Protection Against Peptic Esophageal Disease

• Mechanism: Likely involves hypochlorhydria. • Clinical Note: Individual GERD severity may change post-eradication; treatment should prioritize clear indications.

4.2 Other Pathologies

• Iron Deficiency: Potential cause via occult blood loss or hypochlorhydria. • Idiopathic Thrombocytopenic Purpura: Platelet count may improve post-treatment. • Cardiovascular Disease: Association exists but causality is unproven.

5. DIFFERENTIAL DIAGNOSIS

• Non-NSAID Ulcers: H. pylori is a major risk factor; eradication prevents relapse. • Functional Dyspepsia: Persistent and difficult to treat. • Malignancy Rule-out: Alarm symptoms (e.g., weight loss) require endoscopy.

6. INVESTIGATIONS & DIAGNOSIS

  1. Pre-test Preparation: → Must wait 2 weeks off PPIs. → Must wait 4 weeks off antibiotics/bismuth.
  2. Initial Testing Selection: • Endoscopic Tests: → Biopsy urease: Quick, simple; some not fully sensitive before 24 h. → Histology: Provides additional histologic information; sensitivity depends on experience and special stains. → Culture: Permits determination of antibiotic susceptibility; sensitivity depends on experience. • Noninvasive Tests: → Urea breath test (13C): Inexpensive, simpler than endoscopy; useful for follow-up; requires fasting. → Stool antigen test: Inexpensive, convenient; useful for follow-up; particularly useful in children; some cultures dislike stool-based tests. → Serology: Inexpensive and convenient; not affected by recent antibiotics/PPIs to the same extent as breath/stool; less accurate than breath/stool.
  3. Follow-up Testing: → Perform urea breath or stool antigen test ≥ 1 month after treatment completion to confirm eradication.

6.1 Endoscopy-Based Tests

• Biopsy urease test: Quick, simple; some commercial tests not fully sensitive before 24 h. • Histology: Provides additional histologic information; sensitivity depends on experience and use of special stains. • Culture: Permits determination of antibiotic susceptibility; sensitivity depends on experience.

6.2 Noninvasive Tests

• 13C urea breath test: Inexpensive, simpler than endoscopy; useful for follow-up; requires fasting. • Stool antigen test: Inexpensive, convenient; useful for follow-up; particularly useful in children. • Serology: Inexpensive and convenient; some commercial kits inaccurate; less affected by recent PPIs/antibiotics.

7. MANAGEMENT & TREATMENT

  1. Identify Indications: → H. pylori-related ulcers. → Low-grade gastric MALT lymphoma. → Functional dyspepsia.
  2. Select Treatment Regimen (Table 168-2): • Regimen 1: OCM (14 days) → Omeprazole (20 mg bid), Clarithromycin (500 mg bid), Metronidazole (500 mg bid). • Regimen 2: OCA (14 days) → Omeprazole (20 mg bid), Clarithromycin (500 mg bid), Amoxicillin (1 g bid). • Regimen 3: OBTM (14 days) → Omeprazole (20 mg bid), Bismuth subsalicylate (2 tabs qid), Tetracycline HCl (500 mg qid), Metronidazole (500 mg tid). • Regimen 4: Concomitant (14 days) → Omeprazole (20 mg bid), Amoxicillin (1 g bid), Clarithromycin (500 mg bid), Tinidazole (500 mg bid). • Regimen 5: OAL (10 days) → Omeprazole (20 mg bid), Amoxicillin (1 g bid), Levofloxacin (500 mg bid or 200 mg bid).
  3. Follow-up: → Wait ≥ 1 month post-treatment. → Perform urea breath or stool antigen test to confirm eradication.

8. PROGNOSIS & COMPLICATIONS

• Ulcer Management: Eradication prevents ulcer recurrence. • MALT Lymphoma Prognosis: → Depends on translocation status. → Non-translocated cases may regress with eradication.

8.1 Monitoring

• Success Confirmation: Use urea breath or stool antigen tests post-treatment. • MALT Lymphoma Evaluation: Requires histologic evaluation for translocations to guide therapy.

9. SPECIAL CONSIDERATIONS

• Pediatric Considerations: → Less common in children but may cause iron deficiency. → Treatment must account for weight-based dosing and potential resistance.

10. KEY PEARLS & CLINICAL TRAPS

• Diagnostic Clues: → Weight loss, anemia, or dysphagia → require upper endoscopy to exclude malignancy. • Exclusion Criteria (Testing): → Do not test within 2 weeks of PPIs. → Do not test within 4 weeks of antibiotics/bismuth.

Reference Tables

TABLE 168-1 Tests Commonly Used to Detect Helicobacter pylori TEST Tests Based on Endoscopic Biopsy Biopsy urease test…

Harrison's 22e, p.1301

TEST ADVANTAGES DISADVANTAGES
Tests Based on Endoscopic Biopsy
Biopsy urease
test		 Quick, simple Some commercial tests not
fully sensitive before 24 h
Histology May give additional histologic
information		 Sensitivity dependent on
experience and use of
special stains
Culture Permits determination of
antibiotic susceptibility		 Sensitivity dependent on
experience
Noninvasive Tests
Inexpensive and convenient;
not affected by recent
antibiotics or proton pump
inhibitors to the same extent
as breath and stool tests
Inexpensive and simpler
than endoscopy; useful for
follow-up after treatment
Inexpensive and convenient;
useful for follow-up after
treatment; may be particularly
useful in children

Harrison's 22e, p.1302

REGIMENa (DURATION) DRUG 1 DRUG 2 DRUG 3 DRUG 4
Regimen 1: OCM (14 days)b Omeprazole (20 mg bidc) Clarithromycin (500 mg bid) Metronidazole (500 mg bid) —
Omeprazole (20 mg bidc) Clarithromycin (500 mg bid) Amoxicillin (1 g bid)
Regimen 3: OBTM (14 days)d Omeprazole (20 mg bidc) Bismuth subsalicylate
(2 tabs qid)		 Tetracycline HCl (500 mg qid) Metronidazole (500 mg tid)
Omeprazole (20 mg bidc) Amoxicillin (1 g bid) Clarithromycin (500 mg bid)
Regimen 5: OAL (10 days)g Omeprazole (20 mg bidc) Amoxicillin (1 g bid) Levofloxacin (500 mg bid or 200 mg bid) —