long-term neurological impairment [46]. The antithrombotic, anti-inflammatory and anti- ischaemic effects of aspirin may reduce the risk of new infarcts and strokes [53]. The SURE trial will use a factorial design to secondarily randomise to aspirin versus placebo. Treatment of MDR-TB The treatment of MDR-TB has evolved rapidly with the introduction of new agents, use of repurposed drugs, and the transition from injectable agents to shorter and all-oral regimens. The all-oral 6-month regimen containing bedaquiline, pretomanid, linezolid and moxifloxacin (BPaLM) is the preferred option for adolescents 14 years with MDR-TB without (or with unknown) fluoroquinolone resistance. The BPaLM regimen was found to be noninferior to conventional treatment and was safe, with better treatment success of 89% versus 52% [54]. In the absence of paediatric safety or pharmacokinetic data, pretomanid is currently not approved for use in children 14 years. For younger children, regimens can be constructed by first using WHO group A drugs (linezolid, bedaquiline and a fluoroquinolone (levofloxacin or moxifloxacin)), group B drugs (clofazimine and cycloserine) and then any additional group C drugs to generate a regimen containing four to five effective drugs. Several groups suggest that children with severe disease can be treated for 9–12 months, while those with nonsevere disease can be treated for 6–9 months [55–57]. Bedaquiline and delamanid are now both recommended for use in children of all ages [27]. Safety data were similar to adult cohorts and model-derived dosages informed recommendations for use in children of all ages. Bedaquiline-containing regimens were associated with improved survival rates and favourable safety profiles in observational studies [58, 59]. Pharmacokinetic and safety data for delamanid show no safety concerns when given to children 3 years of age [25, 58]. For children and adolescents not on ART, HIV treatment should be initiated within 2 weeks of TB treatment initiation, except for TBM, where ART should be postponed for 4–8 weeks due to the high risk of immune reconstitution inflammatory syndrome. Follow-up and monitoring TPT The WHO recommends that children and adolescents on TPT should have treatment follow-up monthly (if on a 3-month regimen) or every other month (if on a 6-month regimen). During follow-up visits, the child should be evaluated for adherence to treatment, TB symptoms and adverse events. Weight should be measured to adjust medication dosages if needed. It is important to record all children and adolescents initiating TPT. This is crucial for monitoring drug uptake (stock monitoring), adherence and outcomes of treatment. Electronic registers and databases are recommended by the WHO for collecting individual-level data to assess contacts of TB patients and PLHIV, and to monitor TPT initiation and completion [27, 36]. TB disease Children should be assessed regularly for clinical progress, adherence, side-effects and dosage adjustments [25, 58]. Those with persistent symptoms should be assessed for other comorbidities, as well as exclusion of treatment failure. Children generally respond positively to DS-TB treatment with a very low risk (5%) of serious adverse reactions [39, 60–63], while outcomes for children treated for MDR-TB are also very good [64]. Up to 10% of children treated for TB experience subclinical and transient elevations of transaminases, and routine liver function monitoring is not recommended except in cases where the https://doi.org/10.1183/2312508X.10025322 225 CHILDREN AND ADOLESCENTS |E. LÓPEZ-VARELA ET AL.