Article
Author: Dominguez, José ; Nitschke, Martin ; Oral, Haluk Barbaros ; Martinez, Leonardo ; Goletti, Delia ; Avsar, Korkut ; Altet-Gomez, Neus ; Bakken Kran, Anne-Marte ; Crudu, Valeriu ; Matteelli, Alberto ; Palacios-Gutiérrez, Juan José ; Pedersen, Ole Skouvig ; Rupp, Jan ; Dyrhol-Riise, Anne Ma ; Kalsdorf, Barbara ; Hoffmann, Harald ; Lange, Berit ; Bothamley, Graham ; Nordholm Breschel, Anne Christine ; de Souza Galvao, Malu ; Milkiewicz, Piotr ; Chesov, Dumitru ; Toader, Corina ; Villar-Hernandez, Raquel ; van Leth, Frank ; Petruccioli, Elisa ; Duarte, Raquel ; Ibraim, Elmira ; Neyer, David ; Arias-Guillén, Miguel ; Ciobanu, Nelly ; Lange, Christoph ; Ravn, Pernille ; Cirillo, Daniela Maria ; Lipman, Marc ; Kunst, Heinke ; Wagner, Dirk ; Sester, Martina ; Raszeja-Wyszomirska, Joanna ; Dilektasli, Asli Görek ; Spohn, Hanna-Elisa ; Andersen, Åse Bengaard ; Brown, James ; Krawczyk, Marcin
Background:In low tuberculosis (TB)-endemic countries, tuberculosis preventive therapy (TPT) is recommended for immunocompromised individuals with a positive immunodiagnostic test. This study aimed to assess the performance of the QuantiFERON-TB Gold Plus (QFT+) assay and predictive power for future tuberculosis in immunocompromised individuals.
Methods:In this prospective observational study, immunocompromised adults ≥18 years of age including people living with HIV (PLHIV), chronic renal failure, rheumatoid arthritis, solid-organ transplantation or stem-cell transplantation, and immunocompetent adults with and without TB-disease were recruited at 21 sites in 11 European countries and tested with the QFT+ assay. Individuals without TB-disease were followed up for the development of tuberculosis. TB incidence rates (IR) were calculated, stratified by QFT+ results and acceptance of TPT. This study is registered with Clinicaltrials.gov, NCT02639936.
Findings:A total of 2663 individuals (1115 female, 1548 male) were enrolled from 03/11/2015 to 29/03/2019. Persons without tuberculosis were followed up for at least two years. Among 1758 immunocompromised individuals without active tuberculosis, 13.6% had positive QFT+ results. Sensitivity and specificity for TB-disease were 70.0% (52.1-83.3%) and 91.4% (89.6-92.9%), respectively, in immunocompromised, and 81.4% (76.6-85.3%) and 96.0% (92.5-97.9%), respectively, in immunocompetent individuals. During 2457 cumulative years of follow-up among 932 individuals with chronic renal failure, rheumatoid arthritis, solid-organ transplantation or stem-cell transplantation, including 83 persons with a positive QFT+ test without TPT, no-one developed active tuberculosis. In contrast, among 642 PLHIV without TPT, one with an indeterminate QFT+ and 3/30 individuals with a positive QFT+ developed active tuberculosis; all had detectable HIV-replication and low CD4 T-cell counts (incidence 4.1 (95% CI (1.3-12.4) per 100 person-years). No individuals receiving TPT developed active tuberculosis during 269 years of follow-up.
Interpretation:In immunocompromised individuals in low TB-endemic countries, the 2-year-risk for active tuberculosis was highest among PLHIV with detectable HIV-replication and low CD4-counts. In this study, the QFT+ assay did not strongly predict progression to active tuberculosis, which emphasises the need to incorporate additional risk factors.