Performance of immune-based and microbiological tests in children with tuberculosis meningitis in Europe: a multicentre Paediatric Tuberculosis Network European Trials Group (ptbnet) study
AuthorRoy, RB; Thee, S; Blazquez-Gamero, D; Falcon-Neyra, L; Neth, O; Noguera-Julian, A; Lillo, C; Galli, L; Venturini, E; Buonsenso, D; ...
Source TitleEuropean Respiratory Journal
PublisherEUROPEAN RESPIRATORY SOC JOURNALS LTD
University of Melbourne Author/sTebruegge, Marc
Document TypeJournal Article
CitationsRoy, R. B., Thee, S., Blazquez-Gamero, D., Falcon-Neyra, L., Neth, O., Noguera-Julian, A., Lillo, C., Galli, L., Venturini, E., Buonsenso, D., Gotzinger, F., Martinez-Alier, N., Velizarova, S., Brinkmann, F., Welch, S. B., Tsolia, M., Santiago-Garcia, B., Kruger, R. & Tebruegge, M. (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 (1), https://doi.org/10.1183/13993003.02004-2019.
Access StatusOpen Access
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.
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