Children constitute up to a fifth of patients with tuberculosis in high-incidence countries and account for 8–20% of tuberculosis-related deaths in high-incidence countries.1, 2, 3, 4 Challenges in tuberculosis diagnosis and, consequently, the timely initiation of treatment lead to poor outcomes and can often have fatal consequences for young children. Children with tuberculosis tend to have a relatively low bacterial burden (paucibacillary disease), which makes detecting the organism difficult, even in patients with advanced disease. This paucibacillary nature of childhood tuberculosis leads to poor sensitivities (10–30%) of currently available pathogen-based tests, including nucleic acid amplification or microbiological culture assays.5, 6 This limitation is compounded by the challenge of collecting respiratory specimens from young children suspected of having pulmonary tuberculosis who are unable to expectorate sputum, whether spontaneous or induced. Children have higher incidence of extrapulmonary tuberculosis than in adults7 and the diagnostic challenges of specimen collection and pathogen detection for childhood cases are greater. Symptom-based diagnostic approaches are suboptimal in young children and have even less diagnostic value in children living with HIV.8 Currently available tuberculosis immune-based tests—eg, the tuberculin skin test and blood test (T-SPOT, Oxford Immunotec, USA; and QuantiFERON-TB, QIAGEN, USA)—do not distinguish between infection and disease or past versus present disease, and a negative test does not rule out tuberculosis.9
In the absence of positive pathogen-based tests—ie, culture or nucleic acid amplification tests such as Xpert MTB/RIF (Cepheid, USA)—most cases of childhood tuberculosis are diagnosed on the basis of findings suggestive of tuberculosis disease (eg, clinical signs and symptoms, radiological or medical imaging, laboratory and histopathological findings), or findings supportive of tuberculosis as the cause (eg, exposure history, immune-based tests, biomarkers for systemic inflammation, cell counts, biochemistry), and exclusion of alternative diagnoses. Access to imaging is insufficient in many low-resource settings, although chest radiography is often used in the diagnostic evaluation as complementary evidence of tuberculosis. However, there are limitations in the sensitivity, specificity, and predictive values of chest radiography for diagnosing tuberculosis. HIV co-infection can confound radiological diagnosis because of the occurrence of other co-infections or HIV-associated diseases, such as lymphocytic interstitial pneumonitis or neoplasia.10, 11 Therefore, the US National Institutes of Health convened a workshop at the Union World Conference on Lung Health (October, 2018, The Hague, Netherlands) to identify knowledge gaps in imaging approaches and to develop a roadmap for research for childhood tuberculosis.
Key points
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Chest radiography continues to be a useful imaging modality for the initial radiological evaluation of children with suspected intrathoracic tuberculosis. To distinguish tuberculosis from other pathologies, chest radiography interpretation should be limited to findings such as the detection of the Ghon complex, miliary nodules, and airway compression, and it is important to recognise its limitations.
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Currently available imaging modalities, such as ultrasound and cross-sectional imaging, can improve the diagnostic accuracy of intrathoracic tuberculosis. When available, cross-sectional imaging such as CT, should be considered in the diagnostic evaluation for tuberculosis in a symptomatic child.
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Educating the public and clinicians about the risks and benefits of using available imaging modalities could lead to more pragmatic implementation.
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Novel molecular imaging modalities have the potential to improve diagnostics and provide new insights into disease pathogenesis.
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Substantially increased and sustained support for basic and translational research is needed to develop and translate novel imaging tools for childhood tuberculosis.
