ADOPT RaPaed-TB—A diagnostic signature for paediatric tuberculosis
Tuberculosis (TB) remains one of the leading causes of death among children, particularly among very young and immunocompromised boys and girls. Around 250,000 children die each year, mostly due to missed diagnosis. Microbiological confirmation is rare, while other available tests are neither child-friendly nor accurate enough. The RaPaed-TB study examined 975 children across five countries to evaluate the accuracy of various non–sputum-based methods and novel diagnostic tests. The current project, "ADOPT RaPaed-TB," builds on these data and the collected biobank samples. Analyses of host-based markers (e.g., certain proteins or gene activities in the blood) and pathogen-based targets are planned. These include cell-free DNA in the blood and pathogen detection in stool and urine. By applying advanced technologies, such as artificial intelligence and machine learning, typical patterns of tuberculosis in children will be identified in this data. These new diagnostic approaches will then be compared with existing methods, tested in further studies, and ultimately translated into user-friendly tests for everyday clinical use.
An estimated 1.2 million children fall ill with TB each year, but only about half of them are diagnosed and treated. Among children under five, nearly 70 percent of cases remain undetected. However, treatment is highly effective. If started in time, more than 99 percent of children survive. Without treatment, nearly every second child dies. Overall, this results in approximately 250,000 deaths worldwide each year.
Difficult diagnosis with current tests
The available tests are not suitable for children. They require sputum, or mucus from the respiratory tract, which children have difficulty coughing up. Additionally, the tests are inaccurate and unavailable in many places. Diagnosis therefore relies on symptoms and chest X-rays, which are not precise. The WHO has highlighted the urgent need for simple, rapid tests that work well in children without using sputum.
ADOPT RaPaed-TB: Three priorities for better diagnoses
The ADOPT RaPaed-TB project builds on the large RaPaed-TB study, completed in 2023, which investigated better ways to diagnose TB in children. The international study was coordinated in Munich and conducted in South Africa, Mozambique, Tanzania, Malawi, and India. A total of 975 children were included in the study. The study tested a blood test with a three-gene signature, urine and stool tests, and a novel immune cell marker.
In ADOPT RaPaed-TB, we now aim to use these valuable samples and data to develop improved diagnostics. Our work will focus on three areas:
- New blood markers: We are looking for patterns of gene activity and proteins that can indicate tuberculosis (transcriptomic and proteomic signatures).
- Sputum-free tests: We are developing urine, stool, and blood tests that can directly detect TB bacteria.
- Data combination: We combine all available data—clinical, laboratory, and biomarker results. Then, we evaluate these data using modern methods, such as artificial intelligence, machine learning, and Bayesian models, to identify highly accurate diagnostic signatures.
By building on proven methods and using cutting-edge analysis, our goal is to create child-friendly TB tests that are fast, reliable, and suitable for use in different healthcare settings—helping more children receive the diagnosis and treatment they need.
