New study tests non-sputum tools to diagnose TB in children

Tuberculosis remains a major cause of illness and death in children and adolescents, with an estimated 172,000 deaths in 2024. Diagnosing TB in young people is especially difficult: collecting sputum or other respiratory samples from children can be hard, and infections in children often have very low numbers of bacteria, which makes tests less likely to find the disease. To address these challenges, S. M. LaCourse and colleagues have designed the Pediatric TB Diagnostic (PDTBDx) cohort study. PDTBDx is a prospective observational study that will enroll more than 400 children under 15 years old who come to inpatient and outpatient clinical sites in Nairobi, Kenya with symptoms suggestive of TB. The study focuses on non-sputum-based approaches to both diagnosis and monitoring of treatment response. Rather than reporting final results, this paper lays out the study protocol and methods so that the clinical assessments, sample collection and follow-up are transparent and standardized from the start.

The PDTBDx protocol sets out a thorough baseline and follow-up evaluation for each enrolled child. Baseline tests include a standardized symptom assessment, chest x-ray, HIV testing, respiratory TB culture and GeneXpert Ultra, and urine LAM. Participants are followed closely at week 2, months 1, 2, 4, 6,12 and 24 to track clinical course and treatment response. Blood and urine specimens are collected at baseline and at follow-up visits and stored for later evaluation of new diagnostic approaches, including exosome-based and CRISPR-based TB biomarkers. Diagnostic classification for each child will be made using the NIH consensus statement guidelines for pediatric TB to ensure consistent case definitions. As a prospective cohort with preplanned specimen banking and a rigorous clinical framework, PDTBDx is designed to test and compare multiple non-sputum assays against established respiratory culture and GeneXpert Ultra results.

By building a large, well-characterized cohort of children with suspected TB and following them for up to two years, PDTBDx aims to create the evidence needed to evaluate non-sputum diagnostics in real-world pediatric care. Non-sputum tests such as urine LAM and novel blood- or urine-based biomarkers (including exosome-based and CRISPR-based assays) have the potential to overcome the practical barriers of obtaining respiratory samples from young children. The study’s use of consistent diagnostic classification and longitudinal follow-up means researchers can examine both initial diagnostic accuracy and how biomarkers change with treatment. While the protocol paper does not report diagnostic outcomes, it makes clear that assays evaluated in PDTBDx will be compared within an internationally recognized framework and could inform which non-sputum tests are most useful for diagnosing and monitoring TB in children.