Demographic and Clinical Correlates of Discordant QuantiFERON TB Gold Tuberculosis Screening Results in a Low Endemicity Setting

Interferon-{gamma} Release Assays (IGRAs), such as the QuantiFERON-TB Gold Plus (QFTTB) and T-SPOT.TB, are commonly used to detect prior exposure to Mycobacterium tuberculosis complex (Mtb), the causative agent of tuberculosis (TB). IGRA positive (IGRA+) asymptomatic individuals are diagnosed with presumed latent tuberculosis infection (LTBI) and often offered therapy to prevent progression to active disease. However, discordant results during serial or confirmatory IGRA testing pose challenges for interpretation and may lead to unnecessary LTBI treatment. We conducted a retrospective study of subjects who received QFTTB testing at Stony Brook Medicine between October 2020 and March 2024, focusing on discordant serial testing, to identify sociodemographic and clinical variables associated with quantitative QFTTB results. Variables measured included age, sex, race, comorbidities, and medication use. A total of 743 subjects were analyzed, including all 436 QFTTB-positive (QFTTB+) cases of 11,641 tests ordered (3.7%), of whom 16 were diagnosed with active TB. A random sample of 307 age-sex-matched QFTTB-negative controls were included. Of 203 subjects undergoing serial QFTTB testing, 170 (83.7%) had concordant results, while 33 (16.3%) showed discordance--23 (69.7%) with reversion and 10 (30.3%) with conversion. Conversions occurred in significantly older subjects (mean age 51.1 {+/-} 15.0 vs. 37.0 {+/-} 15.6, p = 0.025) and over longer intervals (415.1 vs. 91.2 days, p = 0.026). Comorbidities including cardiovascular disease, infections, and diabetes correlated with changes in NIL, TB1, and TB2 values. These findings highlight inconsistencies in QFTTB testing that complicate LTBI management and underscore the importance of confirmatory testing in low-incidence settings. Importance StatementReliable interpretation of interferon-{gamma} release assays (IGRAs) is critical for the diagnosis and management of latent tuberculosis infection (LTBI). However, variability in test performance, particularly during serial or confirmatory testing, complicates clinical decision-making and may result in unnecessary treatment. Our study demonstrates that demographic factors, clinical comorbidities, and testing intervals contribute to discordant QuantiFERON-TB Gold Plus (QFTTB) results. These findings underscore the need to integrate epidemiologic risk, clinical history, and repeat testing before initiating therapy, especially in low-incidence regions where the pre-test probability of infection is low. Improved understanding of IGRA variability can strengthen both patient care and research applications, including TB vaccine and biomarker studies.