Discordance between tuberculin skin tests (TST) and interferon gamma release assays (IGRAs): Are we over-treating LTBI?

Background: The identification and treatment of latent TB infection (LTBI) is essential to reduce reactivation and limit disease transmission. TSTs and IGRAs are integral to the UK National Institute for Health and Clinical Excellence (NICE) diagnostic guidelines for LTBI, where either positive test is sufficient to diagnose LTBI. In 2016, the positive TST cut-off was reduced from >10mm if previous BCG to >5mm regardless of BCG status. The impact of this change on diagnostic accuracy is unclear. Aim: Assess the impact of the change in NICE guidelines on the LTBI population and the rate of discordant TST/ IGRA results. Methods: Records of all patients treated for LTBI over 3 years, spanning before and after the guideline change, were reviewed. A positive TST (as per the relevant NICE guidelines) with a negative IGRA result was defined as “discordant”. Results: LTBI cases increased following the guideline change (60 in 2015 vs. 212 in 2016-17). The rate of discordant TST/IGRAs also increased (11.6% of LTBI cases in 2015 vs. 34.4% in 2016-17). In 2016-17, White British patients, who may be more likely to have received the BCG, formed a greater proportion of the “discordant” than total LTBI population (41.2% vs. 24.5%), while new entrants to the UK comprised a lower proportion of the discordant group (2.7% vs. 13.7%). Patients screened prior to anti-TNF therapy formed a greater proportion of the “discordant” than total LTBI group (24.7% vs. 15.6% in 2016-17). Conclusion: Our LTBI patient population grew after the NICE guideline change. A 5mm TST cut-off may not be sufficiently specific for the diagnosis of LTBI in the UK, which has implications for TB services.