Capturing recent Mycobacterium tuberculosis infection by tuberculin skin test vs. interferon-gamma release assay

Reductions in tuberculosis (TB) incidence and mortality require identification of individuals at high risk of developing active disease, such as those with recent Mycobacterium tuberculosis (Mtb) infection. Current tests used for Mtb infection cannot distinguish recent from remote infection. Using a longitudinal, prospective household contact (HHC) study in Kampala, Uganda, we diagnosed new Mtb infection using both the tuberculin skin test (TST) and interferon-gamma release assay (IGRA) to determine if these tests differentiated or added value as measures of recent Mtb infection. We identified 13 HHCs who only converted the IGRA (QFT-only converters), 39 HHCs who only converted the TST (TST-only converters), and 24 HHCs who converted both tests (QFT/TST converters). Univariate analysis revealed that TST-only converters were older than the other groups. This result was confirmed by our logistic regression model where increased odds of TST-only conversion was associated with age (p=0.02), in addition to crowdedness (p=0.025). The odds of QFT conversion increased with a higher epidemiologic risk score (p=0.038), which suggests it is a better measure of Mtb exposure and infection. QFT/TST converters had higher QFT quantitative values at conversion than QFT-only converters and a bigger change in TST quantitative values at conversion than TST-only converters. Collectively, these data indicate that TST conversion alone likely overestimates Mtb infection. Its correlation to older age suggests boosting of BCG responses and/or longer environmental mycobacterial exposure. This result also suggests that QFT/TST conversion may be associated with a more robust immune response, which should be considered when planning vaccine studies.