Exploring non-sputum biosignatures for tuberculosis triage and diagnosis in children living with HIV.

introductionPediatric tuberculosis (TB), especially among children co-infected with HIV, remains a significant global health challenge. Traditional sputum-based diagnostics are less effective in this population due to difficulties in sample collection and paucibacillary disease, necessitating alternative non-sputum diagnostic approaches. AREAS COVERED: This review examines recent advances in non-sputum biosignatures for pediatric TB diagnosis, including host- and pathogen-based biomarkers detectable in blood, urine, stool and breath. EXPERT OPINION: Despite rapid advances in TB biosignature discovery, translation into usable diagnostics lags behind - especially for children and those with HIV. Studies often exclude these key populations, lack diverse validation, and depend on complex laboratory platforms. Bridging this gap requires early integration of feasibility, usability, and health system factors into product development. Multimodal, point-of-care tools adapted for low-resource settings and inclusive of high-risk children are essential. Implementation science and technology adaptation are critical to ensure real-world impact of these promising innovations.To summarize, non-sputum biosignatures offer an opportunity for early diagnosis of TB in children with HIV. However, these signatures need to be validated and be translated into affordable point-of-care tools that can be integrated with current diagnostic approaches and implemented in low resource settings.