Children affected by tuberculous meningitis (TBM), as well as their families, have needs that lie at the intersections between the tuberculosis and meningitis clinical, research, and policy spheres. There is therefore a substantial risk that these needs are not fully met by either programme. In this narrative review article, we use the World Health Organization (WHO) “Defeating Meningitis by 2030: global roadmap” as a starting point to consider key goals and activities to specifically defeat TBM in children. We apply the five pillars outlined in the roadmap to describe how this approach can be adapted to serve children affected by TBM. The pillars are (i) prevention; (ii) diagnosis and treatment; (iii) surveillance; (iv) support and care for people affected by meningitis; and (v) advocacy and engagement. We conclude by calling for greater integration between meningitis and TB programmes at WHO and at national levels.

Background: Early diagnosis of tuberculous meningitis (TBM) is critical to favorable outcomes. We investigated whether a 3-gene host response signature in whole blood can distinguish TBM from symptomatic controls in children. Methods: Whole-blood RNA sequencing was performed in children with TBM and controls. Expression of the 3-gene signature, [guanylate-binding protein (GBP5), dual specificity phosphatase 3 (DUSP3) and Krupple-like factor 2 (KLF2)] was quantified and a tuberculosis (TB) score was calculated using (GBP5+DUSP3)/2-KLF2. Discriminatory performance was obtained using receiver-operator characteristic curve analysis against microbiologic and composite reference standards. TB score and 3-gene expression in children were compared against adults with TBM. In parallel, an exploratory transcriptome-wide analysis was performed, applying bootstrapped least absolute shrinkage and selection operator regression to identify additional genes associated with TBM. Results: Forty-two children had TBM and 41 were controls. KLF2 was upregulated in TBM compared to controls ( P = 0.043); while GBP5, DUSP3 and TB score showed no difference. The diagnostic performance of GBP5 alone (area under the curves: 0.64; 95% confidence interval: 0.46–0.83) and TB score (area under the curves: 0.59; 95% confidence interval: 0.41–0.77) was poor against the reference standard of definite TBM. GBP5 in children with TBM was lower than in adults without HIV (median 13.04; interquartile ranges: 11.91–14.29 vs. median 13.72; interquartile ranges: 12.58–14.53, P = 0.036), and expression was nonlinear across the age spectrum; lowest in young children. Exploratory transcriptomic analysis suggests that novel genes may contribute a discriminatory signal. Conclusion: The 3-gene host response signature does not discriminate TBM from controls in children and was much less discriminative compared to adults. An alternative set of pediatric-specific signatures may exist, but further discovery and validation are required.