Medical Research Council (MRC)
National Institute for Health and Care Research
Professor Diana Gibb – MRC Clinical Trials Unit at University College London
Dr Angela Crook – MRC Clinical Trials Unit at University College London
Professor Guy Thwaites
2019 – now
TB meningitis (TBM) remains a challenging disease to diagnose and treat, particularly in young children. About one in five children who get TBM die of the disease, and about three in five who survive will suffer long-term disability. The global burden of TBM in children is likely to be under-recognised.
In 2022, the World Health Organization (WHO) made a conditional recommendation that an intensified 6-month TB drug regimen could be used as an alternative to the standard of 12 months. Evidence for this shortened intensified regimen comes from a systematic review and meta-analysis of observational studies showing reduced mortality in children with TBM. The 6-month TB drug regimen uses TB drugs at higher doses and with better brain penetration and is the standard treatment for drug-susceptible TBM in some countries. Halving the treatment time would potentially have large benefits for families and health systems. However, there has been no large randomised controlled trial to directly compare the six-month against the 12-month regimen.
Arterial ischaemic stroke is the main cause of irreversible neurological damage in children with TBM and is not prevented by adjunctive corticosteroids. Infarction may already exist at presentation, but many infarcts develop during treatment. Cerebral vasculitis due to hyperinflammation, in addition to hypercoagulability, are contributing factors in the pathogenesis of brain damage in childhood TBM. Aspirin may have a role in the treatment of TBM due to its anti-inflammatory and anti-thrombotic properties. Adjunctive anti-inflammatory treatment to complement the short-term survival benefits of corticosteroids has been proposed and evaluated in a small number of clinical trials. However, results have been inconclusive to date. Larger RCTs evaluating the effect of high-dose aspirin on mortality and neurodevelopmental outcomes in children with TBM are needed.
Study sites in Viet Nam
International study sites