Comparison of Tuberculin Skin Testing and Interferon-γ Release Assays in Predicting Tuberculosis Disease
Authors: Ayers Tracy , Hill Andrew N. , Raykin Julia , Mohanty Sarita , Belknap Robert W. , Brostrom Richard , Khurana Renuka , Lauzardo Michael , Miller Thaddeus L. , Narita Masahiro , Pettit April C. , Pyan Alexandra , Salcedo Katya L. , Polony Araxi , Flood Jennifer ,   CDC Tuberculosis Epidemiologic Studies Consortium, Pascopella Lisa , Ahmed Amina , Aiona Kaylynn , Lovato Juanita , Reves Randall , Trujillo Leti , Garfein Richard , Farrow Laura , Stout Jason , Zavala Sofia , Blumberg Henry , Tapia Jane , Oladele Alawode , Largen Angela , Dorman Susan , Maltas Gina , Munk Elizabeth , Shah Maunank , Ayala Aurimar , Cronin Wendy , Saleeb Paul , Haas Michelle , Sorri Yoseph , Kozik Christine , Moore Marisa , Keh Chris , Romo Laura , Li Joanne C , Reynolds-Bigby Stephanie , Seraphin Marie Nancy , Board Amy , Gallups Jeremy , Stockbridge Erica , Horne David , Atchley Kristen , Maruri Fernanda , Sterling Timothy , Kerrigan Amy , Wright Alicia , Lyon Kursten , Turner Debra 
Published: April 2024

Importance

Elimination of tuberculosis (TB) disease in the US hinges on the ability of tests to detect individual risk of developing disease to inform prevention. The relative performance of 3 available TB tests—the tuberculin skin test (TST) and 2 interferon-γ release assays (IGRAs; QuantiFERON-TB Gold In-Tube [QFT-GIT] and SPOT.TB [TSPOT])—in predicting TB disease development in the US remains unknown.

Objective

To compare the performance of the TST with the QFT-GIT and TSPOT IGRAs in predicting TB disease in high-risk populations.

Design, Setting, and Participants

This prospective diagnostic study included participants at high risk of TB infection (TBI) or progression to TB disease at 10 US sites between 2012 and 2020. Participants of any age who had close contact with a case patient with infectious TB, were born in a country with medium or high TB incidence, had traveled recently to a high-incidence country, were living with HIV infection, or were from a population with a high local prevalence were enrolled from July 12, 2012, through May 5, 2017. Participants were assessed for 2 years after enrollment and through registry matches until the study end date (November 15, 2020). Data analysis was performed in June 2023.

Exposures

At enrollment, participants were concurrently tested with 2 IGRAs (QFT-GIT from Qiagen and TSPOT from Oxford Immunotec) and the TST. Participants were classified as case patients with incident TB disease when diagnosed more than 30 days from enrollment.

Main Outcomes and Measures

Estimated positive predictive value (PPV) ratios from generalized estimating equation models were used to compare test performance in predicting incident TB. Incremental changes in PPV were estimated to determine whether predictive performance significantly improved with the addition of a second test. Case patients with prevalent TB were examined in sensitivity analysis.

Results

A total of 22 020 eligible participants were included in this study. Their median age was 32 (range, 0-102) years, more than half (51.2%) were male, and the median follow-up was 6.4 (range, 0.2-8.3) years. Most participants (82.0%) were born outside the US, and 9.6% were close contacts. Tuberculosis disease was identified in 129 case patients (0.6%): 42 (0.2%) had incident TB and 87 (0.4%) had prevalent TB. The TSPOT and QFT-GIT assays performed significantly better than the TST (PPV ratio, 1.65 [95% CI, 1.35-2.02] and 1.47 [95% CI, 1.22-1.77], respectively). The incremental gain in PPV, given a positive TST result, was statistically significant for positive QFT-GIT and TSPOT results (1.64 [95% CI, 1.40-1.93] and 1.94 [95% CI, 1.65-2.27], respectively).

Conclusions and Relevance

In this diagnostic study assessing predictive value, IGRAs demonstrated superior performance for predicting incident TB compared with the TST. Interferon-γ release assays provided a statistically significant incremental improvement in PPV when a positive TST result was known. These findings suggest that IGRA performance may enhance decisions to treat TBI and prevent TB.