Validation of treatment decision algorithms for childhood tuberculosis at low levels of healthcare in high burden countries - effectiveness, implementation, and integration into policy and practices

Childhood tuberculosis (TB) remains globally underdiagnosed and untreated. In 2022, WHO conditionally recommended the use of treatment decision algorithms (TDAs) to improve the diagnosis of pulmonary TB in children <10 years and called for the external validation of two suggested TDAs for children. The Decide-TB project aims to generate evidence for the implementation of a comprehensive TDA-based approach for TB in children living in high-burden, resource-limited countries, at district hospital and primary health centre levels, and to facilitate the integration of this evidence into practice and policy. As an interdisciplinary consortium of researchers and national TB programs (NTPs), we will conduct a programmatic pilot of WHO-suggested TDAs, also integrating specific TDAs for children living with HIV and/or those malnourished, and severity assessment for shorter treatment decision in non-severe TB disease. Clinical mentoring tools and a Clinical Decision Support System will be developed. District information systems will be strengthened to collect individual data for program monitoring and supervision by NTPs, and for research. The TDA-based approach will be tested in a pragmatic stepped wedge cluster-randomized trial, including effectiveness, implementation, socio-behavioural, economics and policy research components. The diagnostic accuracy of TDAs will be assessed in a parallel meta-analysis of children with presumptive TB from recent studies led by consortium members. The pragmatic trial and meta-analysis will contribute to external validation of the WHO-suggested TDAs. Engagement of key stakeholders and decision-makers throughout the project will support adoption into international and national policies and into clinical practice. Through validation of TDAs, widespread policy adoption, and translation into clinical practice, Decide-TB will increase access to safe and effective TB management for children, thus reduce TB mortality and contribute to SDG3.