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Updated: Feb 12, 2026
Breath Collection from Children for Disease Biomarker Discovery
Published on: February 14, 2019
Protocol for a biomarker discovery study to identify correlates of risk for future tuberculosis disease progression
Melissa Shea Hamilton1,2, Iena P Derks3, Myrsini Kaforou4,2
1Department of Infectious Disease, Imperial College London, London, England, UK s.hamilton@imperial.ac.uk.
Insights
This study identifies biomarkers in young children exposed to tuberculosis (TB) to predict disease progression. Early detection of Mycobacterium tuberculosis (Mtb) infection allows for targeted TB preventive treatment (TPT).
Area of Science:
- Pediatric infectious diseases
- Tuberculosis research
- Biomarker discovery
Background:
- Young children and those with HIV are highly susceptible to tuberculosis (TB) progression and mortality.
- Early identification of sub-clinical TB disease is crucial for effective TB preventive treatment (TPT).
- Biomarker analysis can identify children with viable Mycobacterium tuberculosis (Mtb) at high risk of disease progression.
Purpose of the Study:
- To identify host biosignatures predicting TB disease progression in children under 5.
- To analyze biomarker changes during Mtb infection and early TB disease treatment.
- To improve targeted TPT strategies for high-risk pediatric populations.
Main Methods:
- Utilizing samples from well-phenotyped pediatric cohorts in South Africa.
- Employing multi-omics approaches: transcriptomics, proteomics, metabolomics, and serology.
- Integrating viral co-infections and clinical data with targeted Mtb antibody analysis.
Main Results:
- Analysis of host blood profiles across the TB continuum from Mtb exposure to disease.
- Identification of potential biosignatures for predicting progression to overt TB disease.
- Evaluation of biomarker changes in children receiving treatment for Mtb infection or early TB disease.
Conclusions:
- The INTREPID study aims to establish predictive biosignatures for TB progression in young children.
- Findings will inform the development of novel diagnostic tests for early TB detection.
- This research will enhance the efficiency and targeting of TPT in high-burden settings.
Introduction:
Young children and children living with HIV are at high risk of progressing to tuberculosis (TB) disease following Mycobacterium tuberculosis (Mtb) exposure and infection, and also of developing severe forms of disease and TB-related mortality. Identifying children who have very early (sub-clinical) TB disease, prior to progression to clinically apparent TB, would mean that TB preventive treatment (TPT) could be more efficiently targeted to this group. Identifying biomarker changes on drug therapy in children with Mtb infection or very early disease could pave the way for the development of tests that can identify which children have viable bacilli and are therefore at increased risk of disease progression.
Methods And Analysis:
The INTREPID study will use already collected samples taken from well-phenotyped paediatric cohorts in three clinical studies conducted in South Africa in children <5 years, including a drug-resistant TPT trial (TB-CHAMP), an observational household contact study (interferon-gamma release assay studies) and a prospective diagnostic study (Umoya), all conducted in a setting with a high burden of TB and HIV. We will employ transcriptomic, proteomic, metabolomic and serology approaches to analyse changes in host blood profiles at every stage along the TB continuum, from Mtb exposure to disease and from children treated for Mtb infection and early TB disease, as well as targeted Mtb antibody analysis. Data on viral co-infections and relevant clinical and epidemiological parameters will be integrated and evaluated to identify the optimal biosignatures that can predict future progression to clinically overt disease in children below 5 years of age, including those living with HIV.
Ethics And Dissemination:
The study protocol received ethical approval from the Stellenbosch University Health Research Ethics Committee (N23/03/025). The study findings will be disseminated through peer-reviewed publications, scientific conferences and formal presentations to healthcare professionals and to local communities, in collaboration with the Desmond Tutu TB Centre Community Advisory Board.
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