Report of a WHO expert consultation on dosing to enable implementation of treatment recommendations in the WHO consolidated guidelines on the management of TB in children and adolescents

The World Health Organization’s (WHO’s) Global Tuberculosis (TB) Programme convened a Guideline Development Group (GDG) meeting in May–June 2021 to review questions on the management of TB in children and adolescents. Based on the evidence reviewed, WHO conditionally recommended the use of bedaquiline in children with multidrug- or rifampicin-resistant TB (MDR/RR-TB) aged below 6 years, as part of shorter and longer regimens, and the use of delamanid in children with MDR/RR-TB aged below 3 years, as part of longer regimens. In addition, a 6-month intensive regimen (6HRZEto) was conditionally recommended for use in children and adolescents with bacteriologically confirmed or clinically diagnosed tuberculous meningitis (TBM) (without suspicion or evidence of MDR/RR-TB), as an alternative to the currently recommended 12-month regimen (2HRZE/10HR).

Acknowledging the importance of providing dosing guidance to ensure the new WHO recommendations can be implemented at the country level, WHO convened an expert consultation on dosing related to these three new recommendations on 26 and 27 October 2021. The meeting participants reviewed the latest pharmacokinetic, pharmacodynamic and safety data available from recent and ongoing trials on bedaquiline and delamanid and relevant pharmacometrics simulations and dosing strategies for the shorter, intensive TB meningitis regimen in children and adolescents.

This report summarizes presentations, discussions and final advice provided by meeting participants at this expert consultation meeting. This advice was then incorporated into the WHO operational handbook on the management of TB in children and adolescents, published by the Global Tuberculosis Programme, WHO, in March 2022.