Quantitative Interferon-Gamma Releasing Assay in Predicting Tuberculosis in South Korean Military: A Retrospective Cohort Study

Objectives The interferon-gamma releasing assay (IGRA) has been widely used to diagnose latent tuberculosis infection (TBI). However, there are limited data on the association between performance in the IGRA and risk of tuberculosis disease (TBD), as well as on the appropriate IGRA threshold for initiating TBI treatment. Methods The analysis was performed using the IGRA results in the Korean Military Manpower Administration database (January 2017 – December 2021), and TBD cases reported to the Korean Military Medical Command (January 2017 – June 2023). All Korean candidates for 18-month military service underwent the IGRA in the pre-enlistment examination, and enlistees who tested positive (≥0.35 IU/mL) were advised to receive TBI treatment before enlistment. Results From 2017 to 2021, 1,647,941 individuals were screened, with 29,574 testing positive for IGRA. Excluding non-enlistees, namely individuals with TBD before enlistment, 19,387 individuals were IGRA positive and 1,356,324 IGRA negative. Of the positives, 4,351 were excluded due to discontinued or ongoing TBI treatment at or after enlistment. During follow-up of 9,219 untreated and 5,818 treated positive individuals and 1,356,324 negatives, TBD occurred in 22 of the IGRA positive individuals (97.5/100,000 person-years [95% CI 61.1 – 147.7]), predominantly in the untreated group (18 cases, 130.1/100,000 person-years [95% CI 77.1 – 205.7]) compared to the treated group (4 cases, 45.9/100,000 person-years [95% CI 12.5 – 117.4]), while 57 cases occurred in the IGRA negative group (2.8/100,000 person-years [95% CI 2.2 – 3.6]). Elevating the cut-off of IGRA from 0.35 IU/mL to 1.33 IU/mL increased positive predictive value (0.2% vs. 0.4%, p=0.03), with insignificant loss of sensitivity (24% vs. 20%, p=0.69) and decreased numbers needing treatment from 790.5 to 415.3. Conclusion Elevated IGRA levels before enlistment are associated with risk of TBD during military service. It is worth considering raising the IGRA threshold for treatment of TBI in cohorts of healthy, young military individuals.