Natural history and spectrum of disease Children become infected with M. tuberculosis through exposure to an infectious TB source case. It was previously assumed that this was usually someone in their immediate or extended household. However, it is increasingly recognised that substantial transmission occurs in the community [8]. Following infection, the risk of progressing to TB disease is highest in infants and children 5 years of age due to an immune system that is relatively ineffective at controlling M. tuberculosis replication. Disease progression can occur rapidly (within a few weeks), but the risk remains high for up to 2 years after infection [7, 12, 13]. The risk falls to a nadir in children between 5 and 10 years and increases again in adolescents. Adolescent females have a higher incidence than males, but the risk inverts in adulthood [19]. Many factors contribute to this, such as hormonal changes that affect the immune system during puberty, viral coinfections, and sex inequality in access to healthcare and health-seeking behaviour (which has also been linked to increased mortality) [19]. The spectrum of disease in children is diverse and age dependent (see figure 4 in chapter 14 of this Monograph [20]). Most young children present with minimal disease limited to the intrathoracic lymph nodes, which is often subclinical, paucibacillary and rarely transmissible. Some children, however, can present with extensive disease, including parenchymal pathology, or endobronchial disease, which can result from local complications of intrathoracic lymph-node disease. In young children, EPTB, such as miliary TB or TBM, is also more common. With the onset of puberty, TB disease phenotypes switch to adult-type TB, which is characterised by cavities, increased bacillary loads and higher infectiousness [21]. Children living with HIV have an 8-fold increased risk of TB, a risk that remains elevated, even with a relatively high CD4+ count and/or a low or undetectable viral load [22, 23]. It is common for immunocompromised children and adolescents, regardless of their age, to present with more severe forms of disease, similar to those of younger children. Decision making Active case finding TB is both preventable and curable. In order to provide appropriate prevention or treatment for children with infection or disease, the first step is to correctly identify and diagnose them. For this, active or passive case-finding strategies can be used. In passive case finding, TB is identified in an often-symptomatic child or adolescent whose clinical condition has prompted their visit to a health facility. Active case finding involves the practice of evaluating individuals at high risk for TB who have not been brought due to clinical concerns. Active case detection is necessary to close the large case-detection gap characterised by paediatric TB [24]. The WHO’s End TB Strategy includes this intervention as a core component to eradicate TB. It serves several goals. First, early TB detection serves to minimise avoidable delays, thus reducing mortality and improving outcomes. Second, early detection reduces TB transmission by shortening the duration of infectiousness. Third, TPT prevents new TB cases. According to the WHO, active case-finding approaches are indicated for several at-risk groups, with implementation considerations varying based on the context and disease burden (box 1) [26, 27]. Decision making for TPT To make TPT decisions, TBI testing (TST or IGRA) is recommended by the WHO whenever feasible (especially in children 5 years of age) but is not a requirement. TBI tests, although imperfect, have a high positive predictive value when applied to children at high risk of TBI. The 212 https://doi.org/10.1183/2312508X.10025322 ERS MONOGRAPH |THE CHALLENGE OF TB IN THE 21ST CENTURY