Helicobacter pylori Infection Diagnosis

Helicobacter pylori Infection Diagnosis

Invasive tests

H pylori can be detected at endoscopy by histology, culture, or urease tests, each with inherent advantages and disadvantages. All these biopsy based methods for detecting H pylori are lible to sampling error because infection is patchy. Up to 14% of infected patients do not have antral infection but have H pylori elsewhere in the stomach, especially if they have gastric atrophy, intestinal metaplasia, or bile reflux. In addition, after partially effective eradication treatment, low levels of infection can easily be missed by endoscopic biopsy, leading to overestimates of the efficacy of eradication treatment and reinfection rates. Proton pump inhibitors affect the pattern of H pylori colonisation of the stomach and compromise the accuracy of antral biopsy. Consensus guidelines therefore recommend that multiple biopsies are taken from the antrum and corpus for histology and for one other method (either culture or urease testing).

Histology—Although H pylori may be recognised on sections stained with haematoxylin and eosin alone, supplementary stains (such as Giemsa, Genta, Gimenez, Warthin-Starry silver, Creosyl violet) are needed to detect low levels of infection and to show the characteristic morphology of H pylori. An important advantage of histology is that, in addition to the historical record provided, sections from biopsies (or even additional sections) can be examined at any time, and that gastritis, atrophy, or intestinal metaplasia can also be assessed. Biopsy specimens from other parts of the stomach can be retained in formalin to be processed only if antral histology is inconclusive.

Culture—Microbiological isolation is the theoretical gold standard for identifying any bacterial infection, but culture of H pylori can be unreliable. Risks of overgrowth or contamination make it the least sensitive method of detection, and it is the least readily available test for use with endoscopy. Although only a few centres routinely offer microbiological isolation of H pylori, the prevalence of multiresistant strains makes it increasing likely that culture and antibiotic sensitivity testing may become a prerequisite for patients with persistent infection after initial or repeated treatment failure.

Urease tests are quick and simple tests for detecting H pylori infection but indicate only the presence or absence of infection. The CLO test and cheaper “home made” urease tests are of similar sensitivity and specificity. However, the sensitivity of urease tests is often higher than that of other biopsy based methods because the entire biopsy specimen is placed in the media, thereby avoiding the additional sampling or processing error associated with histology or culture. The sensitivity of biopsy urease tests seems to be much lower (~60%) in patients with upper gastrointestinal bleeding, but this can be improved by placing multiple biopsy samples into the same test vial.

Non-invasive tests

Serology
H pylori infection elicits a local mucosal and a systemic antibody response. Circulating IgG antibodies to H pylori can be detected by enzyme linked immunosorbent assay (ELISA) antibody or latexagglutination tests. These tests are generally simple, reproducible, inexpensive, and can be done on stored samples. They have been used widely in epidemiological studies, including retrospective studies to determine the prevalence or incidence of infection.

Individuals vary considerably in their antibody responses to H pylori antigens, and no single antigen is recognised by sera from all subjects. The accuracy of serological tests therefore depends on the antigens used in the test, making it essential that H pylori ELISA is locally validated. In elderly people with lifelong infection, underlying atrophic gastritis has been associated with false negative results. Consumption of non-steroidal anti-inflammatory drugs has also been reported to affect the accuracy of ELISAs.

Antibody titres fall only slowly after successful eradication, so serology cannot be used to determine H pylori eradication or to measure reinfection rates. Although titres of IgM antibodies to H pylori fall with age, there are no reliable IgM assays to indicate recent acquisition, which, since this is usually asymptomatic, makes it difficult to identify cases of primary infection and thus establish possible routes of transmission.

An important advantage of serological methods over other tests for H pylori infection has been the development of simple finger prick tests that use a fixed, solid phase assay to detect the presence of H pylori immunoglobulins. These “near patient tests” (NPT) can be performed in primary care and are much simpler than the C-urea breath test, which is the only other test for H pylori that is currently used as a NPT. However, the accuracy of the serological NPT is lower than that reported for standard ELISA tests using the same antigen preparations. These tests are often used to reassure patients, but to date no studies have compared the accuracy, cost effectiveness, and reassurance value of the C-urea breath test with the serological NPT in primary care.

Urea breath test
Non-invasive detection of H pylori by the C-urea breath test is based on the principle that a solution of urea labelled with carbon- will be rapidly hydrolysed by the urease enzyme of H pylori. The resulting CO2 is absorbed across the gastric mucosa and hence, via the systemic circulation, excreted as CO2 in the expired breath. The C-urea breath test detects current infection and is not radioactive. It can be used as a screening test for H pylori, to assess eradication and to detect infection in children. The similar but radioactive C-urea breath test cannot be performed in primary care.

Faecal antigen test
In the stool antigen test a simple sandwich ELISA is used to detect the presence of H pylori antigens shed in the faeces. Studies have reported sensitivities and specificities similar to those of the C-urea breath test ( > 90%), and the technique has the potential to be developed as a near patient test. The main advantage of the test, however, is in large scale epidemiological studies of acquisition of H pylori in children.



References:
- Robert PH Logan. 2002. ABC OF THE UPPER GASTROINTESTINAL TRACT. London: BMJ Books

Title Post: Helicobacter pylori Infection Diagnosis
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