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

Abstract 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.