microbiology and radiology results. Above a certain risk threshold, treatment initiation is advised. Using these tools, health workers at lower levels of healthcare and with less experience and training can start children on TB treatment. Until recently, most TDAs were developed using expert opinion. In 2021, the WHO commissioned a meta-analysis of individual participant data for their 2022 guidelines, evaluating existing TDAs first before developing an evidence-based TDA. The operational handbook accompanying the 2022 guidelines includes two TDAs (one for those with and one for those without access to CXR) [32]. External validation of these TDAs is underway. TABLE 1 Continued NAATs involve PCR replication of M. tuberculosis DNA allowing detection of M. tuberculosis as well as mutations associated with drug resistance and can be carried out on clinical specimens or cultured samples Xpert TBM/RIF and Xpert MTB/RIF Ultra (Cepheid, Sunnyvale, USA) are widely used tests that identify rifampicin resistance, and Truenat MTB and MTB Plus (Molbio Diagnosis, Goa, India) are additional endorsed NAATs line probe assays are also able to detect a wider range of drug-resistance mutations WGS sequences the entire M. tuberculosis genome and can detect all mutations associated with drug resistance but is currently expensive and largely unavailable outside research studies in high-TB-burden settings General principles: Should be attempted before treatment initiation, although should not delay treatment initiation (particularly of severe forms, including TBM) Obtaining respiratory samples is still valuable in EPTB with a normal CXR as the lung is usually the entry point Challenges exist in collecting samples in high-TB-burden settings (i.e. availability of equipment for sputum induction, ability to rapidly transport specimens, and adequate laboratory facilities, equipment and trained staff) M. tuberculosis antigen Lipoarabinomannan in urine: Recommended by the WHO for child presumptive TB cases, living with HIV Suboptimal sensitivity and specificity Potentially useful additional test as part of a diagnostic approach Radiology CXR: Benefits include wide availability, low cost and ease of testing Challenges include imperfect sensitivity and specificity and inconsistent interpretation Computer-based interpretation is being developed for children 15 years of age Ultrasound: Can be used as a point-of-care test No radiation High intra- and inter-reader variability Limited experience in the diagnosis of TB in children CT and MRI scanning: Best visualisation of intrathoracic pathology, including lymph nodes Expensive and largely unavailable in high-TB-burden settings Large radiation dosage for CT Frequently requires sedation or anaesthetic for younger children Novel biomarkers Transcriptomic and proteomic biosignatures: Ability to distinguish confirmed TB from other diseases in research studies with high performance Expensive and not commercially available Unknown performance in real-world settings May have a place as part of a diagnostic algorithm CNS: central nervous system NTM: nontuberculous mycobacteria M. tuberculosis: Mycobacterium tuberculosis NAAT: nucleic acid amplification test TBM: tuberculous meningitis CT: computed tomography MRI: magnetic resonance imaging. https://doi.org/10.1183/2312508X.10025322 217 CHILDREN AND ADOLESCENTS |E. LÓPEZ-VARELA ET AL.