Interferon- Release Assays Improve the Diagnosis of Tuberculosis and Nontuberculous Mycobacterial Disease in Children in a Country with a Low Incidence of Tuberculosis

Abstract

BACKGROUND: Diagnosis of childhood tuberculosis (TB) is challenging. The widely used tuberculin skin test (TST) may produce -positive results because of cross-reactivity with nontuberculous mycobacteria or bacille Calmette-Guerin vaccination, resulting in unnecessary treatment. Two recently developed interferon- gamma release assays (IGRAs) show good diagnostic accuracy for active TB in adults; pediatric data are limited, particularly in areas with a low incidence of TB. We assessed the diagnostic accuracy of IGRAs for TB in children in an area with a low incidence of TB. METHODS: In a hospital-based study, the diagnostic accuracy of the TST and 2 IGRAs (T SPOT-TB [T-SPOT; Oxford Immunotec] and QuantiFERON-TB Gold In-Tube [QFT-IT; Cellestis]) were assessed in a cohort of 73 children (median age, 39 months); 28 children with bacteriologically confirmed TB were compared with children without TB (23 with bacteriologically confirmed nontuberculous mycobacterial lymphadenitis and 22 with other nonmycobacterial respiratory tract infections). RESULTS: The specificity for TB of QFT-IT was 100% (95% confidence interval [CI], 91%-100%), and the specificity of T-SPOT was 98% (95% CI, 87%-100%), both of which were considerably higher than the specificity of TST (58%; 95% CI, 42%-73%). The specificity of the TST was 10.5% (95% CI, 1%-33%) in children with nontuberculous mycobacterial lymphadenitis and was 100% (95% CI, 83%-100%) in children with other nonmycobacterial respiratory tract infections. The sensitivity of both QFT-IT and T-SPOT was 93% (95% CI, 77%-99%), and the sensitivity of the TST was 100% (95% CI, 88%-100%). Agreement between the IGRAs was 95.6% ( kappa =0.91); 6.8% of the IGRAs showed indeterminate results. CONCLUSIONS: Both IGRAs showed high diagnostic value in bacteriologically confirmed childhood TB. Their advantage in this study, when performed in addition to the TST, was the ability to distinguish -positive TST results caused by nontuberculous mycobacterial disease, thereby reducing overdiagnosis of TB and guiding clinical management.