Diagnostic Performance of Unstimulated IFN-γ (IRISA-TB) for Pleural Tuberculosis: A Prospective Study in South Africa and India.

BACKGROUND: Tuberculous pleural effusion (TPE) is the most common form of extrapulmonary tuberculosis in many settings. The diagnostic performance of the frontline polymerase chain reaction-based GeneXpert MTB/RIF Ultra (Xpert Ultra) remains suboptimal (sensitivity of ∼30%), but data are limited. Improved diagnostic approaches are urgently needed to detect extrapulmonary tuberculosis (EPTB) in tuberculosis (TB)-endemic settings. METHODS: This multicenter, prospective cohort study evaluated the diagnostic performance of a rapid (same-day) interferon gamma rapid immunosuspension assay (IRISA-TB) in patients with presumed TPE from South Africa and India. Participants underwent pleural biopsy, and testing with other available same-day diagnostic assays (adenosine deaminase [ADA], Xpert Ultra, and IRISA-TB) was concurrently undertaken. The reference standard for TB was microbiological and/or histopathological confirmation using pleural fluid and/or pleural biopsy samples. RESULTS: A total of 217 participants with presumed TPE were recruited (106 from South Africa, 111 from India). The sensitivity of IRISA-TB (cut-point 20.5 pg/mL) was significantly better than that of Xpert Ultra (81.8% [70.4-90.2] vs 32.9% [22.1-45.1]; P < .001) and ADA at the 40 IU/mL cut-point used in India (81.8% [70.4-90.2] vs 53.8% [41.0-66.3]; P  = .002). Compared with ADA at the 30 IU/mL cut-point used in South Africa, IRISA-TB had a higher specificity (96.6% [90.3-99.3] vs 87.1% [78.6-93.2]) and a higher positive predictive value (94.7% [85.5-97.3] vs 81.8% [72.4-88.5]). The negative predictive value (NPV; rule-out value) of IRISA-TB was significantly better than that of Xpert Ultra (87.5% [83.2-93.0] vs 64.9% [61.1-68.6]; P < .001) and ADA at the 40 IU/mL cut-point (87.5% [83.2-93.0] vs 74.1% [68.7-79.0]; P < .001). CONCLUSIONS: IRISA-TB demonstrated markedly better sensitivity and NPV than Xpert Ultra and excellent specificity for the diagnosis of TPE. These data have implications for clinical practice in TB-endemic settings.