Can ELISpot replace the tuberculin skin test for latent tuberculosis?

Abstract

Background: Screening and treatment of latent tuberculosis infection (LTBI) prior to anti-tumour necrosis factor alpha (anti-TNF-alpha) therapy has been shown to decrease the incidence of active tuberculosis (TB) by more than 80%, and is recommended by the British Thoracic Society. In the absence of a gold standard test for LTBI, conventional screening currently involves taking a clinical history of risk factors, a chest X-ray and a tuberculin skin test (TST) which can be difficult to interpret in immunosuppressed patients. Alternative cellular immune-based screening tests have been developed to detect Mycobacterium tuberculosis.

Aim: To examine, evaluate and summarize the quality of evidence on the use of interferon gamma release assay (the ELISpot test) in the diagnosis of latent tuberculosis prior to initiation of anti-TNF-alpha and examine the agreement with the tuberculin skin test.

Methods: Ovid Medline, Embase and the Cochrane library were searched using search terms that included tuberculosis, each of the current anti-TNF-alpha biological agents, TST and interferon-gamma release assay. Terms were searched using MeSH (medical subject headings) terms and/or free text where relevant.

Results: Discordance between tuberculin skin test and ELISpot is greater in individuals who have had the bacillus Calmette-Guérin (BCG) vaccination and are taking corticosteroids. ELISpot technique using CFP-10 and ESAT-6 antigens is more sensitive than TST in detecting M. tuberculosis infection in patients taking corticosteroids. ELISpot avoids cross-reaction with BCG, making it a more specific test in this group of patients. Agreement between the tests was found to be fair (72.8% kappa value=0.38).

Conclusion: Tuberculosis resulting from reactivation of latent tuberculosis following treatment with anti-TNF is a continuing problem. Screening reduces the risk but does not eliminate it. Further studies are needed into the cost-effectiveness and sensitivity of ELISpot and the tuberculin skin test in routine clinical practice.