Helicobacter pylori

Primary Author: Couturier, Marc Roger, PhD, D(ABMM).

  • Key Points
  • Diagnosis
  • Algorithms
  • Screening
  • Monitoring
  • Background
  • Pediatrics
  • Lab Tests
  • References
  • Related Topics
  • Videos

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 antigen Serology
Indications
  • Noninvasive test for diagnosis of H. pylori
  • May be used to document test-of-cure
  • Identifies active H. pyloriinfection
  • Noninvasive test for diagnosis of H. pylori
  • May be used to document test-of-cure
  • Identifies active H. pyloriinfection
  • Not recommended for diagnosis of H. pyloriunless 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 detectsH. pylori antigen in stool using monoclonal antibodies
 
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
 
Characteristics
  • High sensitivity (Ferwana, 2015)
  • 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
  • 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 Urease Histology (with or without staining) Culture
Indications Practical, 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

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

  • 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
  • Refer to Key Points section

Previously known as Campylobacter pyloriHelicobacter 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

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 – 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
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.

Helicobacter pylori Breath Test, Adult 2010476
Method: Qualitative Spectrophotometry

Limitations 

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

Limitations 

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

Limitations 

Less accurate in pediatric patients (low sensitivity)

Helicobacter pylori Culture 2006686
Method: Culture/Identification

Limitations 

Not as sensitive as rapid urease testing or histology

Helicobacter pylori by Immunohistochemistry 2003941
Method: Immunohistochemistry

Guidelines

Chey WD, C Y Wong B, Practice Parameters Committee of the American College of Gastroenterology. American College of Gastroenterology guideline on the management of Helicobacter pylori infection. Am J Gastroenterol. 2007; 102(8): 1808-25. PubMed

Koletzko S, Jones NL, Goodman KJ, Gold B, Rowland M, Cadranel S, Chong S, Colletti RB, Casswall T, Elitsur Y, Guarner J, Kalach N, Madrazo A, Mégraud F, Oderda G, H pylori Working Groups of ESPGHAN and NASPGHAN. Evidence-based guidelines from ESPGHAN and NASPGHAN for Helicobacter pylori infection in children. J Pediatr Gastroenterol Nutr. 2011; 53(2): 230-43. PubMed

Malfertheiner P, Megraud F, O'Morain C, Bazzoli F, El-Omar E, Graham D, Hunt R, Rokkas T, Vakil N, Kuipers EJ. Current concepts in the management of Helicobacter pylori infection: the Maastricht III Consensus Report. Gut. 2007; 56(6): 772-81. PubMed

Talley NJ, American Gastroenterological Association. American Gastroenterological Association medical position statement: evaluation of dyspepsia. Gastroenterology. 2005; 129(5): 1753-5. PubMed

General References

Braden B. Diagnosis of Helicobacter pylori infection. BMJ. 2012; 344: e828. PubMed

Braden B. Methods and functions: Breath tests. Best Pract Res Clin Gastroenterol. 2009; 23(3): 337-52. PubMed

Ferwana M, Abdulmajeed I, Alhajiahmed A, Madani W, Firwana B, Hasan R, Altayar O, Limburg PJ, Murad MHassan, Knawy B. Accuracy of urea breath test in Helicobacter pylori infection: meta-analysis. World J Gastroenterol. 2015; 21(4): 1305-14. PubMed

Graham DYates, Rugge M. Clinical practice: diagnosis and evaluation of dyspepsia. J Clin Gastroenterol. 2010; 44(3): 167-72. PubMed

Kindermann A, Lopes AI. Helicobacter pylori infection in pediatrics. Helicobacter. 2009; 14 Suppl 1: 52-7. PubMed

McColl KE L. Clinical practice. Helicobacter pylori infection. N Engl J Med. 2010; 362(17): 1597-604. PubMed

Patel SKumar, Pratap CBhan, Jain AKumar, Gulati AKumar, Nath G. Diagnosis of Helicobacter pylori: what should be the gold standard? World J Gastroenterol. 2014; 20(36): 12847-59. PubMed

Redéen S, Petersson F, Törnkrantz E, Levander H, Mårdh E, Borch K. Reliability of Diagnostic Tests for Helicobacter pylori Infection. Gastroenterol Res Pract. 2011; 2011: 940650. PubMed

Ricci C, Holton J, Vaira D. Diagnosis of Helicobacter pylori: invasive and non-invasive tests. Best Pract Res Clin Gastroenterol. 2007; 21(2): 299-313. PubMed

Tonkic A, Tonkic M, Lehours P, Mégraud F. Epidemiology and diagnosis of Helicobacter pylori infection. Helicobacter. 2012; 17 Suppl 1: 1-8. PubMed

References from the ARUP Institute for Clinical and Experimental Pathology®

Couturier MRoger, Marshall BJ, Goodman KJ, Mégraud F. Helicobacter pylori diagnostics and treatment: could a lack of universal consensus be the best consensus? Clin Chem. 2014; 60(4): 589-94. PubMed

Patil DT, Bennett AE, Mahajan D, Bronner MP. Distinguishing Barrett gastric foveolar dysplasia from reactive cardiac mucosa in gastroesophageal reflux disease. Hum Pathol. 2013; 44(6): 1146-53. PubMed

Powers-Fletcher M, Couturier M. Non-Helicobacter pylori Helicobacter Species Associated with Human Disease: a Primer for the Clinical Microbiology Laboratory. Clinical Microbiology Newsletter. [Accessed: May 2016]

She RC, Wilson AR, Litwin CM. Evaluation of Helicobacter pylori Immunoglobulin G (IgG), IgA, and IgM serologic testing compared to stool antigen testing. Clin Vaccine Immunol. 2009; 16(8): 1253-5. PubMed

Medical Reviewers

Last Update: August 2016