IS GA NPA BAL NPA BAL GA Stool Urine Blood BMA Serosal fluids FNA or biopsy CSF FIGURE 4 Respiratory and nonrespiratory samples for the diagnosis of TB in children. The choice of method depends on the site of disease age acceptability for the child, parents, health workers and other stakeholders feasibility of collecting and preparing specimens in the local context local availability of equipment, consumables and trained personnel and tests. Respiratory samples for the diagnosis of PTB include: expectorated sputum (ES), induced sputum (IS), nasopharyngeal aspirate (NPA), gastric aspirate (GA), stool and bronchoalveolar lavage (BAL) (see table 2). Nonrespiratory samples include: 1) cerebrospinal fluid (CSF) obtained through lumbar puncture for diagnosis of TB meningitis through molecular tests, culture and biochemical analysis and cell counts of the liquid 2) fine-needle aspiration (FNA) biopsy or excision biopsy for the diagnosis of TB lymphadenopathy with histology, molecular tests or culture 3) serosal fluids and tissue (pleural, peritoneal, pericardial or synovial) obtained through a pleural, ascitic, pericardial or joint tap for diagnosis of pleural, abdominal, pericardial and bone/joint TB, respectively 4) bone marrow aspirate (BMA) or blood, in severely ill people with suspected disseminated TB and 5) urine – a clean catch or midstream urine sample for the diagnosis of genitourinary TB (Xpert MTB/RIF) or the detection of lipoarabinomannan antigen in children and adolescents living with HIV. The minimum recommended volumes/weights are 3 mL for ES, IS and BAL 2 mL for NPA 5 mL for GA and blood 10 mL for gastric lavage (GL), CSF and urine 5 g for stool 1 mL for serosal fluids and 1 mL for BMA. The optimal collection times are as follows: for GA, early morning before the child gets out of bed (to avoid emptying of the stomach after peristalsis begins) for ES, IS, GL, NPA and urine, ideally early morning for the rest of the samples, any time. Age groups are: GA and NPA: 7 years ES: 5 years rest of samples: any age. Testing of samples should be carried out according to the WHO-recommended rapid diagnostic tests and specimen types in the 2022 guidelines: Xpert MTB/RIF for all samples Xpert MTB/RIF Ultra for sputum, NPA, GA, stool, CSF and FNA Truenat MTB and MTB Plus and loop-mediated isothermal amplification (TB-LAMP) for sputum and lateral flow urine lipoarabinomannan for urine [27]. Conceptualisation by E. López-Varela artwork by Alberto Rey (with permission). 220 https://doi.org/10.1183/2312508X.10025322 ERS MONOGRAPH |THE CHALLENGE OF TB IN THE 21ST CENTURY