In 2022, the WHO conditionally recommended the use of treatment decision algorithms (TDAs) for treatment decision-making in children

Within the Decide-TB project (PACT ID: PACTR202407866544155, 23 July 2024), we aim to generate an individual-participant dataset (IPD) from prospective TB diagnostic accuracy cohorts (RaPaed-TB, UMOYA and two cohorts from TB-Speed). Using the IPD, we aim to: (1) assess the diagnostic accuracy of published TDAs using a set of consensus case definitions produced by the National Institute of Health as reference standard (confirmed and unconfirmed vs unlikely TB); (2) evaluate the added value of novel tools (including biomarkers and artificial intelligence-interpreted radiology) in the existing TDAs; (3) generate an artificial population, modelling the target population of children eligible for WHO-endorsed TDAs presenting at primary and secondary healthcare levels and assess the diagnostic accuracy of published TDAs and (4) identify clinical predictors of radiological disease severity in children from the study population of children with presumptive TB.

This study will externally validate the first data-driven WHO TDAs in a large, well-characterised and diverse paediatric IPD derived from four large paediatric cohorts of children investigated for TB. The study has received ethical clearance for sharing secondary deidentified data from the ethics committees of the parent studies (RaPaed-TB, UMOYA and TB Speed) and as the aims of this study were part of the parent studies’ protocols, a separate approval was not necessary. Study findings will be published in peer-reviewed journals and disseminated at local, regional and international scientific meetings and conferences. This database will serve as a catalyst for the assessment of the inclusion of novel tools and the generation of an artificial population to simulate the impact of novel diagnostic pathways for TB in children at lower levels of healthcare. TDAs have the potential to close the diagnostic gap in childhood TB. Further finetuning of the currently available algorithms will facilitate this and improve access to care.

Childhood tuberculous meningitis (TBM) is a devastating disease. The long-standing WHO recommendation for treatment is 2 months of intensive phase with isoniazid (H), rifampicin (R), pyrazinamide (Z) and ethambutol (E), followed by 10 months of isoniazid and rifampicin. In 2022, WHO released a conditional recommendation that 6 months of intensified antituberculosis therapy (ATT) could be used as an alternative for drug-susceptible TBM. However, this has never been evaluated in a randomised clinical trial. Trials evaluating ATT shortening regimens using high-dose rifampicin and drugs with better central nervous system penetration alongside adjuvant anti-inflammatory therapy are needed to improve outcomes.

The Shortened Intensive Therapy for Children with Tuberculous Meningitis (SURE) trial is a phase 3, randomised, partially blinded, factorial trial being conducted in Asia (India and Vietnam) and Africa (Uganda, Zambia and Zimbabwe). It is coordinated by the Medical Research Council Clinical Trial Unit at University College London (MRCCTU at UCL). 400 children (aged 29 days to

Local ethics committees at all participating study sites and respective regulators approved the SURE protocol. Ethics approval was also obtained from UCL, UK (14935/001). Informed consent from parents/carers and assent from age-appropriate children are required for all participants. Results will be published in international peer-reviewed journals, and appropriate media will be used to summarise results for patients and their families and policymakers.

ISRCTN40829906 (registered 13 November 2018).