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Performance of immune-based and microbiological tests in children with tuberculosis meningitis in Europe: a multicentre Paediatric Tuberculosis Network European Trials Group (ptbnet) study

Basu Roy, R; Thee, S; Blázquez-Gamero, D; Falcón-Neyra, L; Neth, O; Noguera-Julian, A; Lillo, C; ... Tebruegge, M; + view all (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. European Respiratory Journal , 56 , Article 1902004. 10.1183/13993003.02004-2019. Green open access

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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.

Type: Article
Title: Performance of immune-based and microbiological tests in children with tuberculosis meningitis in Europe: a multicentre Paediatric Tuberculosis Network European Trials Group (ptbnet) study
Open access status: An open access version is available from UCL Discovery
DOI: 10.1183/13993003.02004-2019
Additional information: Copyright ©ERS 2020. This version is distributed under the terms of the Creative Commons Attribution Licence 4.0.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
URI: https://discovery.ucl.ac.uk/id/eprint/10127138
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