Basu Roy, Robindra; Thee, Stephanie; Blázquez-Gamero, Daniel; Falcón-Neyra, Lola; Neth, Olaf; Noguera-Julian, Antoni; Lillo, Cristina; Galli, Luisa; Venturini, Elisabetta; Buonsenso, Danilo; +10 more... Götzinger, Florian; Martinez-Alier, Nuria; Velizarova, Svetlana; Brinkmann, Folke; Welch, Steven B; Tsolia, Maria; Santiago-Garcia, Begoña; Krüger, Renate; Tebruegge, Marc; ptbnet TB Meningitis Study Group; (2020) Performance of immune-based and microbiological tests in children with tuberculosis meningitis in Europe: a multicentre Paediatric Tuberculosis Network European Trials Group (ptbnet) study. The European respiratory journal, 56 (1). p. 1902004. ISSN 0903-1936 DOI: https://doi.org/10.1183/13993003.02004-2019
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Abstract
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.
Item Type | Article |
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Faculty and Department | Faculty of Infectious and Tropical Diseases > Dept of Clinical Research |
Research Centre |
TB Centre Centre for Maternal, Reproductive and Child Health (MARCH) |
PubMed ID | 32299859 |
Elements ID | 147285 |
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