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Improved treatment for children with tuberculous meningitis: acting on what we know
  1. Jeremy Hill,
  2. Ben Marais
  1. The University of Sydney, Sydney, New South Wales, Australia
  1. Correspondence to Professor Ben Marais, The University of Sydney, Sydney 2145, New South Wales, Australia; ben.marais{at}

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It is estimated that ~1 million children develop tuberculosis (TB) every year,1 with TB now recognised as a top 10 cause of under-5 mortality in TB-endemic areas.2 Despite the scale of the problem, major gaps in TB case detection and prevention persist in high TB incidence countries where most deaths occur, especially in vulnerable young children.3 Tuberculous meningitis (TBM) is recognised as one of the most severe TB manifestations and frequently represents the final ‘terminal pathway’ in children.4 Although TBM is associated with high rates of morbidity and mortality, disease outcomes can be good with early diagnosis and optimal treatment.5 Unfortunately, TBM diagnosis is frequently delayed or unavailable in high TB incidence settings and even if an accurate diagnosis is made, the treatment provided is often suboptimal.

A study by Ruslami et al 6 assessed the pharmacokinetics and tolerability of TBM treatment provided to children aged 0–18 years in Bandung, Indonesia. Plasma and cerebrospinal fluid (CSF) concentrations of isoniazid, rifampicin and pyrazinamide were measured on days 2 and 10 of treatment. Plasma drug exposure was assessed using peak plasma concentrations (Cmax) and total area under the curve (AUC0–24). Participant numbers were small, but the study still provides valuable and critically lacking data, especially on CSF penetration of TBM drugs in children. The 20 patients with TBM included in the study demonstrated large interindividual variability in drug exposure, but all patients had suboptimal rifampicin exposure with very low rifampicin concentrations in their CSF. Four …

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  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Commissioned; externally peer reviewed.

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