Varying Test Cutoffs and Dual Testing as Strategies to Improve the Diagnosis of Latent Tuberculosis Infection in Non-U.S.-born Persons

Abstract

Background: It is unclear if strategies such as using different interferon-gamma release assay (IGRA) cutoffs or performing serial testing with a tuberculin skin test (TST) and an IGRA, or two different IGRAs could improve test accuracy in those from countries with high TB prevalence. Methods: We used Bayesian latent class analysis to construct receiving operating characteristic (ROC) curves and calculate their area under the curve (AUC) based on our cohort of HIV-negative, non-US-born individuals 5 years and older residing in the USA with valid results for all three LTBI tests (i.e TST, Quantiferon Gold-In-Tube (QFT) and T-SPOT.TB (TSPOT)). We compared the sensitivity, specificity and predictive values of 1) standard U.S. cutoffs for test positivity and higher or lower cutoffs, and 2) a single LTBI test and two tests: TST-QFT, TST-TSPOT, QFT-TSPOT. Results: A total of 14,167 participants were included in the analysis. The ROC curves had an AUC of 0.81 (95% Credible Interval (CrI) 0.78 - 0.86), 0.89 (95% CrI 0.86-0.93), and 0.92 (95% CrI 0.88-0.96) for TST, QFT and TSPOT respectively. QFT at the 0.35 IU/ml cutoff and TSPOT at a cutoff of 5 spots made the least number of diagnostic errors. The TST-QFT combination had similar sensitivity, specificity, PPV and NPV to a TST at a cutoff of 8 spots and the TST-TSPOT performed similarly to a QFT at a cutoff of 0.7 IU/mL. Conclusions: Using the lowest IGRA cutoffs performed better in our study population by increasing test sensitivity and NPV, therefore minimizing the total number of diagnostic errors. Two tests performed similarly to single testing with an IGRA at higher cutoffs.