Quantitative interferon-gamma releasing assay in predicting tuberculosis in South Korean military: a retrospective cohort study

Sung-Woon Kang; Jeongjae Lee; Seong Min Kim; Dahye Kang; Euijin Chang; Seongman Bae; Jiwon Jung; Min Jae Kim; Yong Pil Chong; Sang-Oh Lee; Sang-Ho Choi; Yang Soo Kim; Sung-Han Kim

doi:10.1016/j.cmi.2024.04.014

Quantitative interferon-gamma releasing assay in predicting tuberculosis in South Korean military: a retrospective cohort study

Clin Microbiol Infect. 2024 Apr 30:S1198-743X(24)00211-8. doi: 10.1016/j.cmi.2024.04.014. Online ahead of print.

Authors

Sung-Woon Kang¹, Jeongjae Lee², Seong Min Kim³, Dahye Kang¹, Euijin Chang⁴, Seongman Bae⁴, Jiwon Jung⁴, Min Jae Kim⁴, Yong Pil Chong⁴, Sang-Oh Lee⁴, Sang-Ho Choi⁴, Yang Soo Kim⁴, Sung-Han Kim⁵

Affiliations

¹ Department for Infection Control, Armed Forces Daejeon Hospital, Daejeon, Republic of Korea.
² Department of Military Service Examination, Gyeongin Regional Military Manpower Administration, Suwon, Republic of Korea.
³ Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Armed Forces Capital Hospital, Seongnam, Republic of Korea.
⁴ Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
⁵ Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea. Electronic address: kimsunghanmd@hotmail.com.

PMID: 38697393
DOI: 10.1016/j.cmi.2024.04.014

Abstract

Objective: 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 to December 2021), and TBD cases reported to the Korean Military Medical Command (January 2017 to 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 nonenlistees namely individuals with TBD before enlistment, 19 387 individuals were IGRA positive and 1 356 324 IGRA negative. Of the positives, 4351 were excluded due to discontinued or ongoing TBI treatment at or after enlistment. During follow-up of 9219 untreated and 5818 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]), whereas 57 cases occurred in the IGRA-negative group (2.8/100 000 person-years [95% CI, 2.2-3.6]). Elevating the cutoff 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.

Discussion: 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.

Keywords: Epidemiology; Latent tuberculosis; Military medicine; QuantiFERON; Screening.