Summary

Helicobactor pylori commonly infects Australians and can cause gastritis, peptic ulcer disease and gastric cancer. Several non-invasive and invasive (requiring endoscopy) diagnostic tests are available. Non-invasive tests (breath tests or serology) are indicated when endoscopy is not required.

Introduction
Helicobacter pylori is a spiral gram negative bacterium found in association with human gastric epithelial cells (see 'Helicobacter pylori: current concepts and recommendations for treatment' Aust Prescr 1992;15:3-4). Infection of the gastric mucosa by H. pylori results in chronic antral gastritis and subsequently atrophic gastritis. Furthermore, H. pylori is a major pathogenic agent in duodenal and gastric ulcer disease, and has recently been implicated in gastric cancer and lymphoma. Sero-epidemiological studies show that 30-40% of the Australian-born adult population are infected with H. pylori. The prevalence of infection is even higher in older age groups. The indications for H. pylorie radication and the optimal therapeutic regimen are still evolving1 H. pylorican be detected using a range of non-invasive and invasive tests (Table 1).

Table 1

Properties of current clinical tests for H. pylori

Sensitivity Specificity Availability

Cost (approx.)

Invasive
Histology 95% 98% A $70
Culture 90% 100% D $32
Urease test 90% 95% A $1.50
Non-invasive
IgG serology14C or 13C urea 80-95% 80-95% A $14
breath test 95% 98% C $75

A = excellent C = satisfactory

B = good D = poor

Non-invasive tests

Breath tests
Several tests are based on the ability of H. pylori to produce urease. This enzyme catalyses the degradation of urea to ammonia and bicarbonate. In a breath test, urea that has been labelled with a carbon isotope (13C or 14C) is swallowed. Infected patients rapidly release labelled CO2into their breath. Carbon 14 can be easily quantified using a scintillation counter. Carbon 13 has the advantage of being non-radioactive, but requires more sophisticated equipment for detection. Although the radioactivity of 14C appears to be minimal, particularly with new protocols using 37 kBq (1 micro Curie) dosage, 13C breath tests should be used in pregnant women and children. Breath tests have a sensitivity of about 95% and specificity of nearly 100%. The breath test usually becomes negative within one month after eradication of H. pylori and is particularly useful for assessing the efficacy of treatment.

Serology
H. pylori infection causes a local and a systemic immune response. The presence of H. pylori can be shown by detecting specific IgG and IgA antibodies in the serum. A number of different serological tests are now commercially available and used routinely in diagnostic laboratories. The sensitivity of these tests is quoted as 80-95% and specificity 80-95%.2

Rapid, cheap, office-based serological tests of serum/whole blood have recently become available. These tests have similar sensitivity/specificity to other serological tests and may be useful in diagnosing H. pylori in a primary care setting. The precise role of these tests in patients with dyspepsia presenting to general practitioners is currently being evaluated.

Serology is not clinically useful for monitoring patients post-H. pylori eradication therapy as antibody titres may persist for many months.

Invasive tests
Invasive tests require upper gastrointestinal endoscopy and biopsy.

Histology
H. pyloricauses chronic active inflammation within the gastric mucosa. Organisms can be seen on haematoxylin and eosin-stained biopsies as well as with special stains including modified Giemsa, Warthin Starry silver and acridine orange. In addition to the stain used, a second factor that influences the histologic detection of H. pylori is the uneven distribution of the organism through the gastric mucosa. Two antral biopsies are generally recommended. Sensitivity and specificity are approximately 95% and 98%.3

Culture
Culture from gastric mucosal biopsies is considered the gold standard of detection. Cultures are grown on selected and non-selected media at 35oC in a moist environment with CO2and hydrogen enrichment and maintained for at least 7 days. Culture of the organisms is particularly useful in identifying pathogenic strains of H. pylori including cytotoxin production. In addition, antimicrobial sensitivity testing can be undertaken. The sensitivity and specificity of the test are approximately 90% and 100%. The sensitivity of this test is diminished if the number of organisms is small, culture techniques are inadequate, or if the patient has recently taken antimicrobial therapy.

Because of the cost and the expertise required for culture of H. pylori, routine assessment is not currently recommended. The need for culture and sensitivity testing occurs in patients in whom initial eradication regimens fail.

Rapid urease test
Gastric mucosal biopsies can be inoculated on to a urea-containing medium and, if H. pylori is present, its urease splits the urea into ammonia and CO2. The ammonia elevates the pH of the medium. This changes the colour of a pH sensitive indicator. Commercially available agar-based tests such as CLO and HUT require up to 24 hours to become positive with about 70% positive within two hours. The sensitivity and specificity of urease tests are comparable to histology.

Table 2

Clinical disease and H. pyloritesting

Indications Test
Dyspepsia
– children/pregnant women Serology
13C urea breath test
– young adults <45 years old

Serology
Urea breath test

– young adults with suspected malignancy or oesophagitis Gastroscopy and biopsy
– older adults >45 years old Gastroscopy and biopsy
Duodenal ulcer
– current
Gastroscopy and biopsy
– previously documented Urea breath test
Gastric ulcer
– post-treatment Gastroscopy and biopsy
Post-Helicobacter treatment
– indication for endoscopy (e.g. complicated ulcer, gastric ulcer) Gastroscopy and biopsy
– no indication for gastroscopy Urea breath test
– failed eradication Gastroscopy and biopsy
– culture and antibiotic sensitivity

Diagnostic strategies
The test(s) employed depend on the patient's age, suspected diagnosis, previous diagnoses and treatment, the need for gastroscopy, local test availability and resources. Table 2 summarises potential approaches to the use of diagnostic testing.

Conclusion
H. pylori infection can be detected by several methods. The choice of a particular test depends on clinical factors, including the need for upper gastrointestinal endoscopy and monitoring of eradication therapy, availability, relative specificity, sensitivity and cost of the test.

References

  1. Lambert J, Badov D. Gastric acid-related disorders: GORD and peptic ulcer disease. Aust Fam Physician 1995;24:1889-91, 1894-6.
  2. Schembri MA, Lin SK, Lambert JR. Comparison of commercial diagnostic tests for Helicobacter pylori antibodies. J Clin Microbiol 1993;31:2621-4.
  3. Lin SK, Lambert JR, Schembri M, Nicholson L, Finlay M, Wong C, et al. A comparison of diagnostic tests to determine Helicobacter pylori infection. J Gastroenterol Hepatol 1992;7:203-9.