Microbiology Prior to starting treatment for TB disease, best practice is to obtain at least one and preferably several samples for microbiological evaluation in an attempt to isolate M. tuberculosis (figure 4 and table 2). This serves to both confirm the diagnosis and provide a sample for DST (table 1). Host biomarkers A biomarker is a biological marker that can indicate a disease state, and several biomarkers have been identified to assist in the diagnosis of childhood TB [33, 34]. A seminal article published in 2014 demonstrated that a 51-gene signature could discriminate children with confirmed TB from children with other diseases with high sensitivity and specificity [35]. Ongoing proteomic and transcriptomic work is being carried out by several groups to identify a small number of proteins or genes that retain performance and could be translated into a point-of-care test. It is anticipated that point-of-care tests will be available in the next 5 years. TPT The WHO now recommends several TPT regimens of similar effectiveness and safety, regardless of HIV status (table 3) [27, 36, 37]. Choices depend on availability, guidelines, age and HIV status, preferences, contraindications and child-friendly formulations. For children living with HIV, the most critical component is the composition of the ART regimen. Is the technical quality acceptable? Is the CXR abnormal? Are there CXR features that are very specific to TB? Yes No No No Unreadable Normal Radiologically severe Radiologically nonsevere Radiologically severe Radiologically nonsevere Abnormal features very specific to TB Abnormal features not specific to TB Yes Yes FIGURE 2 Algorithm for CXR interpretation in a child with presumptive PTB. When evaluating a CXR, the first step is to assess the quality of the images to determine whether they are readable. Poor-quality images can lead to over- or underdetection of pathology. Next, the reader must determine whether the CXR is normal or abnormal. A full understanding of paediatric CXR features requires training and practice. The thymus (a physiological feature, usually seen in children 5 years of age) and perihilar vascular markings are commonly misinterpreted as abnormal. CXRs with abnormal findings should be evaluated for the presence of TB-specific features. Additionally, CXR can be used to stratify treatment based on disease severity. Features of nonsevere disease are intrathoracic lymph-node TB without airway obstruction, uncomplicated TB pleural effusion (without empyema or pneumothorax), or paucibacillary, noncavitary disease confined to one lobe of the lungs and without miliary TB. Reproduced and modified from [29] with permission. 218 https://doi.org/10.1183/2312508X.10025322 ERS MONOGRAPH |THE CHALLENGE OF TB IN THE 21ST CENTURY