Demographic and clinical correlates of discordant QuantiFERON TB Gold tuberculosis screening results in a low-incidence setting

ABSTRACT Interferon-γ release assays (IGRAs), such as the QuantiFERON-TB Gold Plus (QFTTB), are commonly used to detect past exposure to Mycobacterium tuberculosis complex ( Mtb ), the cause of tuberculosis (TB). IGRA-positive (IGRA+) asymptomatic individuals are diagnosed with presumptive latent tuberculosis infection (LTBI) and often offered therapy to prevent active disease. However, discordant results during serial testing pose challenges for interpretation and may lead to unnecessary treatment. We conducted a retrospective study of subjects who received QFTTB testing at Stony Brook Medicine between October 2020 and March 2024 to identify sociodemographic and clinical variables associated with quantitative QFTTB results. 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 during the 4-year study period within the context of a reported incidence rate of 3.4/100,000 persons per year in Suffolk County, a region of low TB incidence. A random sample of 307 age-sex-matched QFTTB-negative controls was 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). Our findings reinforce the use of confirmatory or repeat testing before initiating LTBI therapy, particularly when testing intervals are short (<6 months) or results fall near the diagnostic cutoff (0.35 IU/mL). IMPORTANCE Reliable interpretation of interferon-γ release assays (IGRAs) is critical for the diagnosis and management of latent tuberculosis infection (LTBI). However, variability in test performance 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 results. These findings underscore the need to integrate epidemiologic risk, pre-test probability of Mycobacterium tuberculosis complex exposure, clinical history, and repeat testing when appropriate before initiating LTBI therapy. Improved understanding of IGRA variability can strengthen both patient care and research applications, including tuberculosis vaccine and protective biomarker studies.