Clinical Features and Spectrum of Neuroimaging Characteristics At Diagnosis In Pediatric Tubercular Meningitis

Background: Tuberculous meningitis (TBM) in children causes significant mortality and neurodevelopmental morbidity. We describe the clinical and neuroimaging characteristics of children recruited in the SURE trial, an international multi-centre trial of TBM treatment. Methods: SURE is a factorial, phase III randomized controlled trial evaluating the non-inferiority for mortality of shorter intensive 6-month (high-dose rifampicin/isoniazid, pyrazinamide, levofloxacin) versus standard 12-month antituberculosis treatment; and superiority of high dose aspirin versus placebo on neurological disability. Children aged <18 years with presumed drug-susceptible TBM are being enrolled in three African and two Asian countries with follow-up to 72 weeks. The clinical features and findings of neuroimaging (as per local site reporting) are described. Results: Between 3 March 2021 and 1 October 2023, 266 children (females [46%], median age 5 years [IQR 1.2 – 9.9]) were enrolled. Twelve [5%] were HIV infected. Fever was the most common symptom at presentation, seen in 91% (241), followed by lack of playfulness/energy (80%, 213), and poor feeding/appetite (70%, 186). Seizures and focal neurological signs were present in 42%(114) and 35%(93) respectively. At enrolment, 47%, 38%, and 15% had TBM stage I, II and III respectively. Amongst children who had neuroimaging done, the most common abnormalities included pathological meningeal enhancement (64%,109), hydrocephalus (57%,97), tuberculomas (37%,63) and infarcts (33%,56). Conclusion: The majority of children in this largest pediatric TBM treatment trial to date presented with features of severe TBM. Several sub-studies are ongoing, including evaluation of new TB diagnostics, neurocognitive outcome and follow up MRI scans at 24 weeks.