Treatment and outcome in children with tuberculous meningitis - a multi-centre Paediatric Tuberculosis Network European Trials Group study.

INTRODUCTION 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 Multicentre, retrospective study involving 27 paediatric healthcare institutions in nine European countries via an established paediatric TB research network, before and after the 2014 revision of 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 four-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 (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 one 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 unfavourable outcome. DISCUSSION 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