Evaluation of QuantiFERON-TB Gold Plus for Predicting Incident Tuberculosis among Recent Contacts: A Prospective Cohort Study

Screening for latent tuberculosis infection (LTBI) among recent tuberculosis (TB) contacts is an
\nimportant component of TB control, particularly in settings with low TB incidence aiming
\ntowards pre-elimination(1). However, currently available LTBI diagnostics lack sensitivity, and
\nhave poor predictive value for incident TB(2–8) Consequently, prevention of one incident TB
\ncase requires treatment of many for LTBI. This is true for both interferon gamma release assays
\n(IGRAs) and the tuberculin skin test (TST); a recent evaluation found that QuantiFERON Gold-InTube (QFT-GIT; Qiagen, Hilden, Germany) and T-SPOT.TB (Oxford Immunotec, UK) perform
\nsimilarly to the TST when a BCG-stratified TST cut-off is used(8).
\nA newer generation QuantiFERON (QuantiFERON-TB Gold Plus; QFT-Plus) was recently
\nlaunched, adding a second TB antigen tube (TB2) that incorporates short peptides designed to
\nstimulate a CD8+
\n T-cell response, in addition to the CD4+
\n-response tube (TB1) included in
\nprevious versions. The proposed rationale for this is that CD8+
\n-responses have been associated
\nwith mycobacterial load and recent TB exposure(9, 10). Initial independent evaluations have
\nsuggested QFT-Plus may have improved test sensitivity in active TB compared to QFT-GIT(11),
\nand that the CD8+
\n-targeted antigen tube response may be associated with proxy measures of
\ndegree of TB exposure among contacts(12). However, no studies have examined the prognostic
\nvalue of QFT-Plus for predicting incident TB. We aimed to address this key knowledge gap in a
\nprospective cohort of UK TB contacts.