Clinical Question
In adults attending primary care with upper gastrointestinal symptoms, what is the accuracy and utility of point-of-care testing to detect Helicobacter pylori infection?
BACKGROUND AND ADVANTAGES OVER EXISTING TECHNOLOGY
Helicobacter pylori (HP) infection causes approximately 5% of uninvestigated dyspepsia and a 20% lifetime risk of peptic ulcer disease.1 HP is a grade 1 carcinogen: 5.2% of cancers globally are attributable to HP infection.2 HP eradication results in: reduced gastric cancer incidence; prevention of recurrent duodenal (number needed to treat [NNT] = 2) and stomach (NNT = 3) ulceration; and resolution of dyspepsia (NNT = 13).3
Non-invasive Helicobacter pylori diagnostic tests are available for point-of-care (POC) use in primary care and include IgG serology, 13C-urea breath test (UBT), and monoclonal stool antigen. Only UBT is sufficiently accurate to confirm current infection or eradication.4 HP IgG serology cannot differentiate current from past infection. Rapid qualitative stool antigen testing currently lacks diagnostic accuracy.
DETAILS OF TECHNOLOGY
Isotope ratio mass spectrometry (IRMS) is the most commonly used 13C-UBT method in the UK. However, the sampling procedure involves many opportunities for test incompletion: collection of the test from the pharmacy; returning for a subsequent extended appointment; sending the test to the laboratory; and awaiting results. In comparison, non-dispersive isotope selective infrared spectroscopy (NDIRS) has potential as a POC device: it can be used by non-specialist staff outside the laboratory setting, it is relatively inexpensive, and it gives results in 2–5 minutes.4
PATIENT GROUP AND USE
NDIRS may be appropriate for adults presenting to primary care with:1
uninvestigated dyspepsia and no alarm symptoms >4 weeks;
past history of gastric or duodenal ulcer, taking or starting non-steroidal anti-inflammatory drugs (NSAIDS);
unexplained iron-deficiency anaemia, idiopathic thrombocytopenic purpura (ITP), or B12 deficiency with normal colonoscopy and endoscopy; and
need for confirmation of eradication following treatment.
PREVIOUS RESEARCH
Accuracy compared with existing technology
A meta-analysis of studies including adult patients with dyspepsia assessing the diagnostic accuracy of UBTs compared with HP culture and/or histology from biopsy reported pooled sensitivity and specificity of 95% (95% confidence interval [CI] = 93 to 96%) and 93% (95% CI = 91 to 95%), respectively, for NDIRS, with no significant difference from studies reporting IRMS.5 A multicentre study including 41 patients, some with dyspepsia who had not undergone eradication therapy and others with gastric ulceration receiving eradication, found a close correlation between NDIRS and IRMS with an AUROC of 0.96. NDIRS was more sensitive (100% versus 90%) and less specific (89% versus 96%).6
Prior restriction of therapy
Restricting medication prior to testing is necessary to gain an accurate UBT result. NDIRS had a sensitivity of 68% and specificity of 91% in 41 patients who had taken acid suppression or antibiotic medication within 3 days, and a sensitivity of 100% and specificity of 95% at a threshold between 4–5‰ in 182 patients not taking medication within 3 days, when compared with histology.7 Sensitivity was 97% (95% CI = 94 to 100%) and specificity 94% (95% CI = 87 to 100%) in 178 fasted patients who had not received eradication therapy (acid suppression, bismuth preparations, or antibiotics) within 1 month, compared with biopsy culture and stain.8 A sensitivity of 96% and specificity of 99% was reported in 177 patients undergoing endoscopy for dyspepsia if they had taken no eradication therapy within the previous 8 weeks, compared with IRMS.9
Reported thresholds
NDIRS showed 100% agreement at a threshold of 4.0‰ compared with a combined reference standard of 14C-UBT, rapid urease test, and histology in 53 outpatients with duodenal ulceration.10 At 5‰, NDIRS was 98% sensitive and 99% specific compared with IRMS in 538 asymptomatic volunteers;11 79% sensitive and 96% specific in 145 patients compared with a composite reference standard of histology, culture, and rapid urease testing;12 and displayed a sensitivity of up to 100% and specificity of 95% compared with IRMS in a study of 134 fasted dyspeptic patients with non-ulcer dyspepsia (97 cases) or duodenal ulceration (37 cases).13
Impact compared with existing technology
No studies reporting on the impact of POC NDIRS in primary care were retrieved. One large study included 44 487 patients >45 years who met test-and-treat criteria. Breath samples were collected at home and mailed to the laboratory for NDIRS analysis.14 One in five patients tested positive, although 726 samples (1.6%) were not included due to bag errors. The authors concluded that a test-and-treat system involving home testing was feasible.
COST-EFFECTIVENESS
No cost-effectiveness studies have been carried out on POC testing for HP infection in primary care. 13C-UBT testing in dyspeptic patients was found to be cost-effective in one study, with an incremental cost-effectiveness ratio (ICER) of £1000 per quality-adjusted life year compared with not testing at all.15 However, cost-effectiveness studies in other populations have not found 13C-UBT testing to be cost-effective, providing only small health benefits while significantly increasing costs compared with other tests.
RELEVANT GUIDELINES
International guidelines recommend: 1) a 2-week restriction of proton pump inhibitor (PPI) use, and 4 weeks of antibiotics and bismuth compounds, before HP testing; 2) a 13C-UBT ‘test-and-treat’ strategy in patients with uninvestigated dyspepsia without alarm symptoms; 3) testing in aspirin and NSAID users with a history of peptic ulcer; 4) testing and eradication in unexplained iron deficiency anaemia (IDA), ITP, and vitamin B12 deficiency; 5) 13C-UBT retesting >4 weeks after eradication therapy.1
WHAT THIS TECHNOLOGY ADDS
The NDIRS 13C-UBT is more accurate than other non-invasive POC tests for the diagnosis of HP infection and confirmation of HP eradication. It has comparable accuracy with laboratory-based IRMS but has the potential to reduce delays in testing by enabling a rapid diagnosis, prior to treatment initiation. However, the health benefit of this reduction compared with non-POC tests is unclear.
The lack of robust evidence on the comparative accuracy of NDIRS in the primary care setting, and the impact of NDIRS testing on endoscopy demand, need urgent attention.
The available evidence suggests that, for patients with upper gastrointestinal symptoms, primary care-based NDIRS testing may reduce diagnostic delay and could reduce inappropriate prescription of eradication therapy by accurately confirming current infection.
METHODOLOGY
Standardised methodology was applied in writing this report, using prioritisation criteria and a comprehensive, standardised search strategy, and critical appraisal. Full details of these are available from https://www.oxford.dec.nihr.ac.uk/reports-and-resources/horizon-scanning-reports/. The search for this article was conducted in October 2016.
Notes
Funding
This article presents independent research funded by the National Institute for Health Research (NIHR) Diagnostic Evidence Co-operative Oxford. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health. The study sponsors had no role in the design, analyses, or reporting of the study. The researchers retained complete independence in the conduct of this study.
Provenance
Freely submitted; externally peer reviewed.
Competing interests
The authors have declared no competing interests.
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- Received July 12, 2017.
- Revision requested July 20, 2017.
- Accepted August 1, 2017.
- © British Journal of General Practice 2017