Abstract
Introduction Tuberculous meningitis (TBM) is often diagnostically challenging. Only limited data exist on the performance of interferon-gamma release assays (IGRA) and molecular assays in children with TBM in routine clinical practice, particularly in the European setting.
Methods Multicenter, 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 ≥1 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%); 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%), and CSF polymerase-chain-reaction (PCR) in 34.8% (95%CI: 22.9–43.7%). In the subgroup of children who had TST, IGRA, CSF culture and CSF PCR performed 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.
Footnotes
This manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.
Conflict of interest: RB was a consultant for FIND, Geneva, a non-profit organization, from 2014 to 2016.
Conflict of interest: Dr. Thee has nothing to disclose.
Conflict of interest: Dr. Blázquez-Gamero has nothing to disclose.
Conflict of interest: Dr. Falcón-Neyra has nothing to disclose.
Conflict of interest: Dr. Neth has nothing to disclose.
Conflict of interest: Dr. Noguera-Julian has nothing to disclose.
Conflict of interest: Dr. Lillo has nothing to disclose.
Conflict of interest: Dr. Galli has nothing to disclose.
Conflict of interest: Dr. Venturini has nothing to disclose.
Conflict of interest: Dr. Buonsenso has nothing to disclose.
Conflict of interest: Dr. Götzinger has nothing to disclose.
Conflict of interest: Dr. Martinez-Alier has nothing to disclose.
Conflict of interest: Dr. Velizarova has nothing to disclose.
Conflict of interest: Dr. Brinkmann has nothing to disclose.
Conflict of interest: Dr. Welch has nothing to disclose.
Conflict of interest: Dr. Tsolia has nothing to disclose.
Conflict of interest: Dr Santiago-Garcia has received diagnostic assays free of charge for other projects from Cepheid, and support for conference attendance from GlaxoSmithKline.
Conflict of interest: Dr. Krüger has nothing to disclose.
Conflict of interest: Dr Tebruegge has received QuantiFERON assays at reduced pricing or free of charge for other TB diagnostics projects from the manufacturer (Cellestis/Qiagen), and has received support for conference attendance from Cepheid
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- Received October 11, 2019.
- Accepted March 9, 2020.
- Copyright ©ERS 2020