Tojo

Pediatric tuberculosis (TB) presents significant diagnostic difficulties in low- and middle-income countries due to the limited effectiveness and availability of current tests for children. Researchers from multiple institutions in Peru and Bolivia are evaluating a new diagnostic method called CRISPR-TB, which detects circulating Mycobacterium tuberculosis cell-free DNA (cfDNA) in the blood. This approach has shown promising results in pilot studies, with high sensitivity and specificity for identifying TB in children, including those living with HIV. The study aims to enroll 200 children suspected of TB and an equal number of well controls, grouped by age and TB status, to establish and validate cfDNA levels as a biomarker for TB. The study involves recruiting children aged 2 months to 14 years who are evaluated for respiratory symptoms and suspected TB at the Dr. Mario Ortiz Suarez Children's Hospital in Bolivia. Participants will be grouped based on clinical and laboratory findings into confirmed TB, unconfirmed TB, unlikely TB, and well control groups. Several diagnostic tests will be used, including Quantiferon Gold for TB infection, HIV serology, TB culture from respiratory specimens, chest radiographs, lung ultrasounds, and blood tests for cfDNA. Follow-up evaluations and sample collections will occur at 1 week, 2 weeks, and 2 months after treatment initiation for TB cases, while well controls will have a single evaluation. Participants will undergo medical history review, clinical exams, and multiple specimen collections for microbiological and molecular testing. Imaging studies will be analyzed using traditional and advanced automated methods, including machine learning for chest X-rays and lung ultrasounds, to correlate imaging findings with cfDNA levels. The primary outcome is the measurement of cfDNA levels at baseline and 2 months post-treatment in TB cases. Safety and treatment response will be closely monitored throughout the study. The total participation duration includes initial enrollment, follow-up visits during treatment, and data analysis phases extending over several years.