Evaluation of tuberculosis diagnostics in children: 2. Methodological issues for conducting and reporting research evaluations of tuberculosis diagnostics for intrathoracic tuberculosis in children. Consensus from an expert panel

Abstract

Confirming the diagnosis of childhood tuberculosis is a major challenge. However, research on childhood tuberculosis as it relates to better diagnostics is often neglected because of technical difficulties, such as the slow growth in culture, the difficulty of obtaining specimens, and the diverse and relatively nonspecific clinical presentation of tuberculosis in this age group. Researchers often use individually designed criteria for enrollment, diagnostic classifications, and reference standards, thereby hindering the interpretation and comparability of their findings. The development of standardized research approaches and definitions is therefore needed to strengthen the evaluation of new diagnostics for detection and confirmation of tuberculosis in children. In this article we present consensus statements on methodological issues for conducting research of Tuberculosis diagnostics among children, with a focus on intrathoracic tuberculosis. The statements are complementary to a clinical research case definition presented in an accompanying publication and suggest a phased approach to diagnostics evaluation; entry criteria for enrollment; methods for classification of disease certainty, including the rational use of culture within the case definition; age categories and comorbidities for reporting results; and the need to use standard operating procedures. Special consideration is given to the performance of microbiological culture in children and we also recommend for alternative methodological approaches to report findings in a standardized manner to overcome these limitations are made. This consensus statement is an important step toward ensuring greater rigor and comparability of pediatric tuberculosis diagnostic research, with the aim of realizing the full potential of better tests for children.

Figure 1.

Schematic of the disease spectrum within a study population. The large circle represents exposed children, a subset of whom will become infected with Mycobacterium tuberculosis. Of those infected, only a subset develops disease due to M. tuberculosis, and a smaller subset is confirmed microbiologically. Note that a small subset of children with microbiologic confirmation will not have active tuberculosis, as children experiencing an initial infection may have mycobacteremia, which is contained and may never develop symptoms. Also note that children with clinical symptoms consistent with tuberculosis can fall into any of the other circles, including those unexposed to tuberculosis.