Helicobacter pylori

Key Points

Helicobacter pylori Testing

Helicobacter pylori diagnostic testing can be divided into two categories: noninvasive and invasive. No gold standard test exists for the diagnosis of H. pylori. Instead, the test of choice depends upon the clinical scenario, pretest probability of infection, availability, and cost.

Noninvasive Testing ("Test-and-Treat" Strategy*)

  • Only recommended in adults <55 years without alarm symptoms** (ACG, 2007)
  • Not recommended in children – strategy may lead to missed pathology (ESPGHAN and NASPGHAN, 2011)
 Urea breath tests (13C and 14C)Stool antigenSerology
Indications

Noninvasive test for diagnosis of H. pylori

May be used to document test-of-cure

Identifies active H. pylori infection

Noninvasive test for diagnosis of H. pylori

May be used to document test-of-cure

Identifies active H. pylori infection

Not recommended for diagnosis of H. pylori unless other tests are unavailable

Do not use for test-of-cure

Likely will not identify active H. pylori infection

Description
  • Individual drinks citric acid solution containing 13C urea
  • Pre- and post-drinking levels of labelled carbon dioxide are measured
  • Premise – bacterial urease from H. pylori will hydrolyze the labelled 13C urea into labelled carbon dioxide which is easily measurable
  • Individual returns random stool sample for testing
  • Premise – enzyme immunoassay test detects H. pylori antigen in stool using monoclonal antibodies
  • Serum measurements of IgG, IgA
  • Premise – infection with H. pylori will lead to the development of detectable antibodies in serum
Conditions
  • Fasting and abstaining from smoking for 1 hour prior to test 
  • Recommend no proton pump inhibitors (PPIs) x 2 weeks
    • Testing may be performed if patient on PPI but may result in a false negative result
  • No antibiotics or bismuth preparations x 2 weeks
  • No PPIs x 2 weeks
  • No antibiotics x 4 weeks
  • Not influenced by antibiotics or PPIs
Characteristics
  • High sensitivity
  • Unclear specificity for H. pylori
    • Other urease-positive organisms can cause false-positive results
  • Acute bleeding increases risks of false negative test
  • High positive (PPV) and negative (NPV) predictive value
  • Positive result in patient on PPI is reliable; negative result should be confirmed with follow-up test 14 days after discontinuing PPI
  • High sensitivity and specificity
  • Acute bleeding increases risks of false negative test
  • High PPV and NPV
  • PPV is often poor, particularly in regions with low prevalence
  • IgG and IgA are the only serology tests to use (if test is chosen)
  • Cannot be used in individuals with known previous H. pylori infection

INVASIVE TESTING (ENDOSCOPY WITH ANTRAL BIOPSY)

  • Recommended in all adults >55 or in those with alarm symptoms** (ACG, 2007)
  • Test of choice for evaluation of gastrointestinal pathology and symptoms in children (ESPGHAN and NASPGHAN, 2011)
 Rapid UreaseHistology (with or without staining)Culture
IndicationsPractical, cost-effective method of testing for H. pylori
  • Stains may be useful if low colonization suspected
  • Histologic evaluation may identify unsuspected pathology
  • Not usually necessary
  • Recommended in children (ESPGHAN and NASPGHAN, 2011)
  • Recommended if resistance to clarithromycin is suspected
Description
  • Antral biopsy is placed in solution or gel containing urea
  • Color change indicates urease activity, indicative of H. pylori
  • Premise – bacterial urease from H. pylori will hydrolyze the urea to ammonia and the pH will increase reflected by color change
  • Tissue is reviewed by pathologist
  • Addition of stains (eg, Giemsa, Warthin-Starry, hematoxylin and eosin, immunohistochemistry) increase sensitivity
Identifies organism and characterizes antimicrobial sensitivities
Conditions
  • No PPIs x 2 weeks
  • No antibiotics x 4 weeks
  • No PPIs x 2 weeks
    • If PPIs have been used, gastric body biopsies may improve yield
  • No antibiotics x 4 weeks
  • No PPIs x 2 weeks
  • No antibiotics x 4 weeks
Characteristics
  • High sensitivity
  • Not specific to H. pylori
  • Rapid results
  • Inexpensive
  • Acute bleeding increases risks of false negative test
  • Sensitivity significantly reduced in post-treatment setting
  • Sensitivity is subject to area being sampled
  • Expensive
  • Not as sensitive as rapid urease test or histology
  • Isolation of organism is highly variable
  • High specificity
  • Expensive
  • Difficult to perform
  • Most reference laboratories offer culture testing

* Test-and-treat strategy (triple therapy – amoxicillin or metronidazole, clarithromycin, and PPI) is recommended for patients <55 years (Maastricht III Consensus recommends 45 years) with uninvestigated persistent dyspepsia and no alarm symptoms

**Alarm symptoms – gastrointestinal bleeding, unexplained iron deficiency anemia, early satiety, unexplained weight loss, progressive dysphagia, odynophagia, recurrent vomiting, family history of upper gastrointestinal cancer, previous esophagogastric malignancy

Test of Cure

  • Followup is recommended for (Maastricht III Consensus Report)
    • Children
    • H. pylori-associated ulcer
    • Persistent dyspepsia despite test-and-treat strategy
    • H. pylori-associated mucosa-associated lymphoid tissue (MALT) lymphoma
    • Resection for early gastric cancer
    • Non-ulcer dysplasia
    • Atrophic gastritis
    • Gastric lymphomas
    • First-degree relatives of patients with gastric cancer
    • Uninvestigated populations with H. pylori (prevalence >20%)
    • Patients on long-term NSAIDs with a history of gastrointestinal bleeding or peptic ulcer disease
  • Recommended tests
    • Urea breath tests (13C and 14C)
    • Stool antigen
  • Test timing
    • No sooner than 4 weeks after therapy is completed

Diagnosis

Indications for Testing

Laboratory Testing

  • Low-risk populations with prevalence of H. pylori infection <10% – acid-reduction therapy trial is most cost effective (American Gastroenterologic Society)
  • Refer to Key Points section for discussion of testing strategies

Differential Diagnosis

Screening

  • General population screening of asymptomatic patients not recommended
  • Recommended testing
    • Patients with family history of gastrointestinal cancer should be screened if symptomatic (endoscopy with biopsy)
    • Patients without alarm symptoms and dyspepsia who do not respond to acid-reduction therapy may be candidates for H. pylori testing

Monitoring

  • Refer to Key Points section

Clinical Background

Previously known as Campylobacter pylori, Helicobacter pylori (H. pylori) is one of the most common bacterial pathogens in humans.

Epidemiology

  • Prevalence – depends on age, socioeconomic status, and ethnic group
    • ~30-35% of U.S. population and up to 50% of world population
  • Age – incidence increases with age; lowest in young children
  • Transmission – probably fecal-oral

Organism

  • Gram-negative, spiral-shaped, urease-positive, microaerophilic bacterium
    • Survives in acid environment by producing urease that converts urea to ammonia
  • Infects the gastric epithelium and causes chronic inflammation with intestinal metaplasia in most infected hosts

Risk Factors

  • Low socioeconomic status
  • Older age
  • Non-Caucasian ethnicity

Clinical Presentation

  • Dyspepsia – chronic and recurrent pain or discomfort centered in the upper abdomen (epigastrium)
  • Gastritis
  • Abdominal pain
  • Peptic ulcer disease – gastric, duodenal
  • Associated malignancies
    • Gastric mucosa-associated lymphoid tissue (MALT) lymphoma
    • Gastric adenocarcinoma

Pediatrics

Clinical Background

Epidemiology

  • Prevalence – <10% of children <12 years of age infected in developed countries

Clinical Presentation

  • More atypical presentation than in adults
  • Common – diminished eating, recurrent abdominal pain (although most recurrent abdominal pain is not due to H. pylori)
  • Uncommon – epigastric pain, peptic ulcer disease, dyspepsia
    • May present with gastrointestinal bleeding (ulcer usually present)

Diagnosis

Indications for Testing

  • Recurrent or nonspecific abdominal pain
  • Hematemesis, recurrent emesis, epigastric pain

Laboratory Testing

  • Noninvasive
    • Recommended
      • Urea breath test is most reliable test in children
        • Usual cutoff 5%
        • Raising cutoff to 8% increases accuracy in children <6 years
        • Many studies in children recommend its use in diagnosis  
        • Less accurate in youngest children (<6 years, especially infants)
        • Some urea breath tests may not be FDA approved for pediatric samples
      • Stool antigen testing – less accurate than in adults
        • Limited studies evaluating use in children
        • Lower sensitivity in young children (<6 years)
    • Not recommended
      • Serology – varies by test but generally low sensitivity
  • Invasive
    • Endoscopy with histologic examination and/or culture of biopsy remains gold standard
      • Used more often in children because test-and-treat strategies are not validated

Histology

  • Rapid urease activity on tissue specimen
  • Demonstration of organisms by staining (hematoxylin or Giemsa)
  • Immunohistochemistry – H. pylori
  • Culture – high sensitivity

Differential Diagnosis

Monitoring

  • Refer to Monitoring tab

Indications for Laboratory Testing

  • Tests generally appear in the order most useful for common clinical situations
  • Click on number for test-specific information in the ARUP Laboratory Test Directory
Test Name and Number Recommended Use Limitations Follow Up
Helicobacter pylori Breath Test, Adult 0020646
Method: Qualitative Spectrophotometry

Sensitive and specific noninvasive test to diagnose H. pylori infection for adults

Use to confirm eradication of H. pylori at least four weeks following completion of therapy

Do not order for children <17 years

Recommend no proton pump inhibitors (PPIs) x 2 weeks; testing may be performed if patient on PPI but may result in a false negative result

Negative result does not rule out possibility of H. pylori infection; if clinical signs suggest H. pylori infection, retest with new sample or alternate method

This test not currently approved for pediatric samples; for pediatric patients, order H. pylori Breath Test, Pediatric

Negative result in patient on PPI should be confirmed with second breath test 14 days after discontinuing PPI

False-negative results may be caused by

  • Use of proton pump inhibitors antimicrobials, and bismuth preparations during the preceding 2 weeks 
  • Administration of breath test <4 weeks after completion of therapy to eradicate H. pylori
  • Premature or late collection of post-dose sample

False-positive results may be caused by

  • Patient with achlorhydria
  • Procedures for test administration not followed correctly
  • Presence of other gastric spiral organisms such as H. heilmannii

13C and 14C breath tests are noninvasive but expensive due to need for special equipment

 
Helicobacter pylori Breath Test, Pediatric 2010925
Method: Qualitative Spectrophotometry

Pediatric test requires weight, height, gender, and age information

Sensitive and specific noninvasive test to diagnose H. pylori infection for pediatric patients

Use to confirm eradication of H. pylori at least four weeks following completion of therapy

Recommend no proton pump inhibitors (PPIs), antimicrobials, or bismuth preparations x 2 weeks

Post-dose sample must be collected within 13-18 minutes post dose to avoid false-negative results

Negative result does not rule out possibility of H. pylori infection; if clinical signs suggest H. pylori infection, retest with new sample or alternate method

 
Helicobacter pylori Antigen, Fecal by EIA 0065147
Method: Qualitative Enzyme Immunoassay

Sensitive and specific noninvasive alternative to the urea breath test to diagnose H. pylori infection

Use to confirm eradication of H. pylori at least four weeks following completion of therapy

Less accurate in pediatric patients (low sensitivity)

 
Helicobacter pylori Antibodies, IgG & IgA 0050994
Method: Semi-Quantitative Enzyme Immunoassay

Not recommended to diagnose H. pylori; order H. pylori urea breath test or fecal antigen by EIA

If choosing serologic testing despite the above recommendations, IgG serology is preferred

Generally low sensitivity

May require repeat testing if results are equivocal and clinical suspicion present

 
Helicobacter pylori, Culture 2006686
Method: Culture/Identification

Recommended in children to diagnose H. pylori infection

Not as sensitive as rapid urease testing or histology

 
Helicobacter pylori by Immunohistochemistry 2003941
Method: Immunohistochemistry

Aid in histologic diagnosis of H. pylori

Stained and returned to client pathologist; consultation available if needed

   
Additional Tests Available
 
Click the plus sign to expand the table of additional tests.
Test Name and NumberComments
Helicobacter pylori Antibody, IgA 0050995
Method: Semi-Quantitative Enzyme Immunoassay

Not recommended to diagnose H. pylori; order H. pylori urea breath test or fecal antigen by EIA

If choosing serologic testing despite the above recommendations, IgG serology is preferred

Helicobacter pylori Antibody, IgG 0099359
Method: Semi-Quantitative Enzyme Immunoassay

Do not use to diagnose H. pylori; order H. pylori urea breath test or fecal antigen by EIA

Use IgG only if breath and/or stool tests cannot be performed

Helicobacter pylori Antibody, IgM 0098392
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay

Do not use to diagnose H. pylori; order H. pylori urea breath test or fecal antigen by EIA