Advanced imaging tools for childhood tuberculosis: potential applications and research needs

Abstract

Tuberculosis is the leading cause of death globally that is due to a single pathogen, and up to a fifth of patients with tuberculosis in high-incidence countries are children younger than 16 years. Unfortunately, the diagnosis of childhood tuberculosis is challenging because the disease is often paucibacillary and it is difficult to obtain suitable specimens, causing poor sensitivity of currently available pathogen-based tests. Chest radiography is important for diagnostic evaluations because it detects abnormalities consistent with childhood tuberculosis, but several limitations exist in the interpretation of such results. Therefore, other imaging methods need to be systematically evaluated in children with tuberculosis, although current data suggest that when available, cross-sectional imaging, such as CT, should be considered in the diagnostic evaluation for tuberculosis in a symptomatic child. Additionally, much of the understanding of childhood tuberculosis stems from clinical specimens that might not accurately represent the lesional biology at infection sites. By providing non-invasive measures of lesional biology, advanced imaging tools could enhance the understanding of basic biology and improve on the poor sensitivity of current pathogen detection systems. Finally, there are key knowledge gaps regarding the use of imaging tools for childhood tuberculosis that we outlined in this Personal View, in conjunction with a proposed roadmap for future research.

Figure 1:. Optimising the use of currently available imaging techniques

Chest radiography interpretation should be limited to findings such as the detection of the Ghon complex, miliary nodules, and airway compression to distinguish tuberculosis from other pathologies. However, because of the low accuracy of chest radiography for detecting pathologies suggestive of tuberculosis, when available, cross-sectional imaging should be considered in the diagnostic evaluation for tuberculosis in a symptomatic child. Additionally, mediastinal and abdominal ultrasound can be used to improve diagnostic accuracy. 2D=two-dimensional. 3D=three-dimensional.

Figure 2:. Potential applications of advanced imaging tools

(A) The poor sensitivity of current pathogen detection systems, especially for deep-seated infections (not represented by clinical samples such as blood), could be improved by the development and validation of sensitive pathogen-specific imaging technologies. This approach could also allow patient stratification for rigorous evaluation of new diagnostic tools for childhood tuberculosis and to identify patients requiring longer treatments. Repeated imaging could also help to monitor response to treatments. (B) Much of the understanding of infections stems from clinical samples that might not accurately represent the local biology at infection sites. New platforms for basic research incorporating advanced imaging tools could enable the use of an iterative, bidirectional process to integrate findings from animal models and human studies, as well as to validate and refine animal models so that they can address the relevant human pathobiology. Specific molecular imaging approaches that measure the local biology (bacteria, antibiotic concentrations, and microenvironment) could improve understanding of pathogenesis, mechanisms of novel therapeutics, antibiotic treatments, and serve as biomarkers to measure efficacy and treatment responses.