Protocol for a biomarker discovery study to identify correlates of risk for future tuberculosis disease progression in South African children (INTREPID)
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
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 utilize 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 (IGRA 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 (DTTC CAB).
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 utilize 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 (IGRA 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 (DTTC CAB).
Date Issued
2026-02-01
Date Acceptance
2026-01-12
Citation
BMJ Open, 2026, 16 (2)
ISSN
2044-6055
Publisher
BMJ Publishing Group
Journal / Book Title
BMJ Open
Volume
16
Issue
2
Copyright Statement
© Author(s) (or their employer(s)) 2026. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group. https://creativecommons.org/licenses/by-nc/4.0/ This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: https://creativecommons.org/licenses/by-nc/4.0/.
License URL
Identifier
10.1136/bmjopen-2025-099348
Publication Status
Published
Article Number
099348
Date Publish Online
2026-02-10