Host RNA Expression for Diagnosis and Monitoring of Pediatric TB in Africa and India

This study began in December 2018.

Purpose of the study: Improved methods to accurately diagnose childhood TB particularly in populations with high prevalence of HIV and malnutrition, and which can be evaluated on readily accessible samples are urgently needed. An alternative strategy for diagnosis of TB in children is the detection of specific host biomarkers. Changes in biomarker signature in response to treatment have not been studied and may be particularly helpful in better characterizing children in the ‘unconfirmed’ TB group. We hypothesize that treatment-associated changes in the transcriptomic profiles will differ between those children in the ‘unconfirmed’ TB group who had TB and those who had another respiratory illness. Here we propose to leverage the RePORT platform by (1) including a cohort of Indian children together with African children in the large validation study, and (2) doing an exploratory study on changes in gene expression profiles during treatment for TB. 

Study design: This study involves the collaboration of two RePORT consortia, South Africa and India, both high burden TB and TB-HIV settings with well-established pediatric cohorts of children with TB disease, together with the Imperial College group leading the current NIH-supported pediatric TB biomarker validation study.

Study population: Baseline samples from 365 South African children will be tested as part of the existing Levin biomarker validation study and are not budgeted here. Follow up samples from a subset of 200 South African children will be included as part of the proposed study.

Samples from children with confirmed and unconfirmed TB from India are already available and archived in India as part of the RePORT India parent protocol CTRIUMPh conducted at BJMC Pune and NIRT Chennai sites. 

Samples from the 50 children from India with unlikely TB will be newly recruited as part of an add-on “TB screening” pediatric module where 75 children will be recruited for TB screening at the BJMC Pune site.

Primary objectives: To derive and validate a global RNA expression signature for the diagnosis of pulmonary TB, and extra-pulmonary TB in children; and to identify longitudinal changes in RNA expression with TB treatment in children who have microbiologically confirmed or clinically diagnosed TB, using bio-banked samples from the South Africa and Indian cohorts and clinical information from the TB RePORT Common Protocol (CP) and India parent protocol databases.

Secondary objectives: To establish a biorepository of samples that can be used for future pediatric TB diagnostic and pathogenesis studies.