Treatment and Outcome in Children With Tuberculous Meningitis: A Multicenter Pediatric Tuberculosis Network European Trials Group Study
- PMID: 34849642
- DOI: 10.1093/cid/ciab982
Treatment and Outcome in Children With Tuberculous Meningitis: A Multicenter Pediatric Tuberculosis Network European Trials Group Study
Abstract
Background: Currently, data on treatment, outcome, and prognostic factors in children with tuberculous meningitis (TBM) in Europe are limited. To date, most existing data on TBM originate from adult studies, or studies conducted in low-resource settings.
Methods: We designed a multicenter, retrospective study involving 27 pediatric healthcare institutions in 9 European countries via an established pediatric TB research network, before and after the 2014 revision of World Health Organization (WHO) dosing recommendations.
Results: Of 118 children, 39 (33.1%) had TBM grade 1, 68 (57.6%) grade 2, and 11 (9.3%) grade 3. Fifty-eight (49.1%) children received a standard 4-drug treatment regimen; other commonly used drugs included streptomycin, prothionamide, and amikacin. Almost half of the patients (48.3%; 56/116) were admitted to intensive care unit, with a median stay of 10 (interquartile range [IQR] 4.5-21.0) days. Of 104 children with complete outcome data, 9.6% (10/104) died, and only 47.1% (49/104) recovered fully. Main long-term sequelae included spasticity of 1 or more limbs and developmental delay both in 19.2% (20/104), and seizure disorder in 17.3% (18/104). Multivariate regression analyses identified microbiological confirmation of TBM, the need for neurosurgical intervention, and mechanical ventilation as risk factors for unfavorable outcome.
Conclusions: There was considerable heterogeneity in the use of TB drugs in this cohort. Despite few children presenting with advanced disease and the study being conducted in a high-resource setting, morbidity and mortality were high. Several risk factors for poor outcome were identified, which may aid prognostic predictions in children with TBM in the future.
Keywords: children; dosing; outcome; treatment; tuberculous meningitis.
© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.
Conflict of interest statement
Potential conflicts of interest. M. Te. 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. B. G.-S. has received diagnostic assays free of charge for other projects from Cepheid, and support for conference attendance from GlaxoSmithKline (GSK). D. B.-G. has received payments as speaker at conferences from MSD and Roche. M. Ts. has received payments from MSD, Pfizer, Sanofi-Pasteur, and GSK for other clinical studies and participation in advisory boards. F. B. reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from MSD. A. N.-J. reports being supported by Subvencions per a la Intensificació de Facultatius Especialistes (Departament de Salut de la Generalitat de Catalunya, Programa PERIS 2016–2020; ref. SLT008/18/00193). D. B. reports participating at the Qiagen advisory board on IGRAs in children in May 2021. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
