What is Helicobacter pylori?

Helicobacter pylori: A Pathogenic Bacterium with Significant Health Implications

Helicobacter pylori is a gram-negative, microaerophilic bacterium that colonizes the human stomach and is the primary cause of chronic gastritis, peptic ulcer disease, and a significant risk factor for gastric cancer and mucosa-associated lymphoid tissue (MALT) lymphoma. 1, 2

Characteristics and Epidemiology

H. pylori is characterized by:

• Gram-negative, spiral-shaped bacterium with flagella that allow mobility within the gastric mucosa
• Microaerophilic (requires oxygen but at lower levels than atmospheric)
• Produces urease enzyme that neutralizes stomach acid, enabling survival in the harsh gastric environment
• Colonizes the protective mucous layer of the stomach

Prevalence

• Most common chronic bacterial infection worldwide 3
• Affects 50% of the world's population 4
• Higher prevalence (70-90%) in developing countries
• Lower prevalence in developed countries, but with significant variation based on:
  • Socioeconomic status
  • Ethnic background
  • Immigration status

Disease Associations and Clinical Impact

H. pylori infection is associated with:

1. Peptic Ulcer Disease:

   • Lifetime risk of peptic ulcer is approximately 17% among those infected 1
   • Prior to H. pylori discovery, peptic ulcer was considered a chronic disease ("once an ulcer, always an ulcer")
   • H. pylori eradication transforms peptic ulcer from a chronic condition to a curable disease

2. Gastric Cancer:

   • Sixth most common cancer worldwide and third most common cause of cancer death
   • Over 1 million new cases diagnosed in 2020, causing more than 768,793 deaths 1
   • Lifetime risk varies from 0.6% to 22% worldwide
   • Classified as a definite (Class I) carcinogen by the World Health Organization

3. MALT Lymphoma:

   • H. pylori infection is strongly associated with gastric MALT lymphoma
   • Eradication of H. pylori can lead to regression of early-stage MALT lymphoma

4. Chronic Gastritis:

   • Nearly all infected individuals develop chronic gastritis
   • May progress to atrophic gastritis, a precursor to gastric cancer

5. Extragastric Manifestations:

   • Can affect other organ systems including skin, liver, and heart 4
   • May adversely affect nutritional status in both children and adults

Transmission

H. pylori transmission occurs primarily through:

• Person-to-person contact (oral-oral or fecal-oral routes)
• Family clustering is common (infection tends to spread within households)
• Iatrogenic transmission (during endoscopic procedures if equipment is inadequately sterilized)
• No substantial reservoir outside the human stomach 5

Diagnostic Methods

Non-invasive Tests:

• Urea Breath Test (UBT):

  • First-line non-invasive test
  • Sensitivity 94.7%, specificity 95.7%
  • Requires stopping PPIs, antibiotics, and bismuth for 2 weeks before testing 2

• Stool Antigen Test (SAT):

  • Good alternative when UBT unavailable
  • Sensitivity 88.8-92.1%, specificity 87.3-87.6%
  • Less affected by PPI use than UBT 2

• Serology:

  • Not affected by recent use of PPIs, antibiotics, or bismuth
  • Cannot differentiate between active and past infection
  • Requires local validation 2

Invasive Tests (requiring endoscopy):

• Rapid urease test
• Histology
• Culture
• PCR-based molecular testing for antibiotic resistance

Treatment Approach

First-line Treatment:

• Bismuth Quadruple Therapy (BQT) for 14 days is preferred when antibiotic susceptibility is unknown 6

Alternative Regimens:

• Triple therapy with PPI, clarithromycin, and amoxicillin for 14 days 7, 8
• Rifabutin triple therapy or potassium-competitive acid blocker dual therapy for 14 days in patients without penicillin allergy 6

Treatment Challenges:

• Increasing antimicrobial resistance, particularly to clarithromycin, metronidazole, and levofloxacin
• Patients with clarithromycin-resistant H. pylori should not be treated with regimens containing clarithromycin 7, 8
• Post-treatment testing should be performed at least 4 weeks after completion of therapy 2

Public Health Implications

• Countries with high gastric cancer prevalence (Japan, Korea, Taiwan, China) are implementing population-wide H. pylori eradication programs 1
• In the US, certain populations remain at higher risk (Native Americans, African Americans, Hispanics, and immigrants from high-risk countries) 1
• Systematic approaches to identify high-risk individuals are needed for effective gastric cancer prevention 3

Key Considerations for Clinical Practice

• Test for H. pylori in patients with uninvestigated dyspepsia, current or past peptic ulcers, and family history of gastric cancer
• Consider testing family members of patients with proven H. pylori infection
• Confirm eradication with non-invasive testing at least 4 weeks after treatment completion
• Avoid using serology to confirm eradication
• Recognize that successful eradication prevents recurrence of peptic ulcer disease and may reduce gastric cancer risk

The discovery of H. pylori in the early 1980s revolutionized our understanding of gastric diseases, transforming peptic ulcer from a chronic condition into a curable infectious disease and establishing a clear link between bacterial infection and gastric cancer.