TY - JOUR T1 - Performance of immune-based and microbiological tests in children with tuberculosis meningitis in Europe: a multicentre Paediatric Tuberculosis Network European Trials Group (ptbnet) study JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.02004-2019 VL - 56 IS - 1 SP - 1902004 AU - Robindra Basu Roy AU - Stephanie Thee AU - Daniel Blázquez-Gamero AU - Lola Falcón-Neyra AU - Olaf Neth AU - Antoni Noguera-Julian AU - Cristina Lillo AU - Luisa Galli AU - Elisabetta Venturini AU - Danilo Buonsenso AU - Florian Götzinger AU - Nuria Martinez-Alier AU - Svetlana Velizarova AU - Folke Brinkmann AU - Steven B. Welch AU - Maria Tsolia AU - Begoña Santiago-Garcia AU - Renate Krüger AU - Marc Tebruegge A2 - , Y1 - 2020/07/01 UR - http://erj.ersjournals.com/content/56/1/1902004.abstract N2 - Introduction Tuberculous meningitis (TBM) is often diagnostically challenging. Only limited data exist on the performance of interferon-γ release assays (IGRA) and molecular assays in children with TBM in routine clinical practice, particularly in the European setting.Methods Multicentre, retrospective study involving 27 healthcare institutions providing care for children with tuberculosis (TB) in nine European countries.Results Of 118 children included, 54 (45.8%) had definite, 38 (32.2%) probable and 26 (22.0%) possible TBM; 39 (33.1%) had TBM grade 1, 68 (57.6%) grade 2 and 11 (9.3%) grade 3. Of 108 patients who underwent cranial imaging 90 (83.3%) had at least one abnormal finding consistent with TBM. At the 5-mm cut-off the tuberculin skin test had a sensitivity of 61.9% (95% CI 51.2–71.6%) and at the 10-mm cut-off 50.0% (95% CI 40.0–60.0%). The test sensitivities of QuantiFERON-TB and T-SPOT.TB assays were 71.7% (95% CI 58.4–82.1%) and 82.5% (95% CI 58.2–94.6%), respectively (p=0.53). Indeterminate results were common, occurring in 17.0% of QuantiFERON-TB assays performed. Cerebrospinal fluid (CSF) cultures were positive in 50.0% (95% CI 40.1–59.9%) of cases, and CSF PCR in 34.8% (95% CI 22.9–43.7%). In the subgroup of children who underwent tuberculin skin test, IGRA, CSF culture and CSF PCR simultaneously, 84.4% had at least one positive test result (95% CI 67.8%–93.6%).Conclusions Existing immunological and microbiological TB tests have suboptimal sensitivity in children with TBM, with each test producing false-negative results in a substantial proportion of patients. Combining immune-based tests with CSF culture and CSF PCR results in considerably higher positive diagnostic yields, and should therefore be standard clinical practice in high-resource settings.All existing immunological and microbiological TB tests have suboptimal sensitivity in children with TBM. Combining immune-based tests with CSF culture and PCR results in far higher positive diagnostic yields, and should therefore be standard practice. http://bit.ly/2TSAArl ER -