Position statement on interferon-γ release assays for the detection of latent tuberculosis infection.

[Disclaimer: The views expressed in this item are those of the individual authors, and do not necessarily represent the views of the Communicable Diseases Intelligence journal or the Australian Centre for Disease Control. While this Policy and Guidelines item was drafted with consideration to the then-available information on the condition(s) addressed within, it may not be complete and may not represent the currently understood best practice for the referenced condition(s). Readers are advised to refer to the most recent guidance on this matter, where such guidance exists and where its authoritativeness can be established. These guidelines do not replace the need for clinical judgment to be exercised for each individual circumstance, nor the necessity for expert advice to be obtained as appropriate.] Interferon-y release assays (IGRAs), such as the Quantiferon (QIFN) TB-Gold Plus assay (Qiagen, Hilden, Germany) and the T-SPOT.TB test (Oxford Immunotec Limited, Abingdon, United Kingdom), are marketed as a substitute for the tuberculin skin test (TST) for the detection of latent tuberculosis infection (LTBI). The relative merits of IGRAs and TST have been hotly debated over the last decade. The specificity of IGRAs has been optimised by using Mycobacterium tuberculosis-specific antigens. However, IGRAs are functional in vitro T-cell-based assays that may lack reproducibility due to specimen collection, transport, processing and kit manufacturing issues. Longitudinal studies comparing the ability of IGRAs and TST to predict the future development of active tuberculosis disease (TB) are the ultimate arbiters on the respective utility of these assays. Three meta-analyses addressing this comparison have now been published and clinical experience with IGRAs is accumulating. The systematic reviews show that IGRAs and TST have similar (but poor) ability to identify patients with LTBI at risk of developing active TB disease. The improved specificity of IGRAs however may reduce the number of patients requiring preventative therapy. Based on these meta-analyses, The National Tuberculosis Advisory Committee (NTAC) now recommends either TST or an IGRA for the investigation of LTBI in most circumstances. Both tests may be used in patients where the risk of progression to active TB disease is high and the disease sequelae potentially severe (eg. LTBI testing in immunocompromised patients or those commencing anti-tumour necrosis factor-ą (TNF) therapy). Neither test should be used in the investigation of active TB disease (though TST and/or IGRA may be used as supplementary tests in paediatric cases). The choice of test for serial testing in healthcare workers (HCWs) remains controversial. A preference remains for TST in this circumstance because IGRAs have been bedevilled by higher rates of reversions and conversions when used for serial testing. These recommendations supersede all previous NTAC IGRA statements.