Penn-Nicholson, Adam, Mbandi, Stanley Kimbung, Thompson, Ethan, Mendelsohn, Simon C, Suliman, Sara, Chegou, Novel N, Malherbe, Stephanus T, Darboe, Fatoumatta, Erasmus, Mzwandile, Hanekom, Willem A et al (show 19 more authors)
(2020)
RISK6, a 6-gene transcriptomic signature of TB disease risk, diagnosis and treatment response.
SCIENTIFIC REPORTS, 10 (1).
8629-.
Abstract
Improved tuberculosis diagnostics and tools for monitoring treatment response are urgently needed. We developed a robust and simple, PCR-based host-blood transcriptomic signature, RISK6, for multiple applications: identifying individuals at risk of incident disease, as a screening test for subclinical or clinical tuberculosis, and for monitoring tuberculosis treatment. RISK6 utility was validated by blind prediction using quantitative real-time (qRT) PCR in seven independent cohorts. Prognostic performance significantly exceeded that of previous signatures discovered in the same cohort. Performance for diagnosing subclinical and clinical disease in HIV-uninfected and HIV-infected persons, assessed by area under the receiver-operating characteristic curve, exceeded 85%. As a screening test for tuberculosis, the sensitivity at 90% specificity met or approached the benchmarks set out in World Health Organization target product profiles for non-sputum-based tests. RISK6 scores correlated with lung immunopathology activity, measured by positron emission tomography, and tracked treatment response, demonstrating utility as treatment response biomarker, while predicting treatment failure prior to treatment initiation. Performance of the test in capillary blood samples collected by finger-prick was noninferior to venous blood collected in PAXgene tubes. These results support incorporation of RISK6 into rapid, capillary blood-based point-of-care PCR devices for prospective assessment in field studies.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Adolescent Cohort Study team, GC6-74 Consortium, SATVI Clinical and Laboratory Team, ScreenTB Consortium, AE-TBC Consortium, RePORT Brazil Team, Peruvian Household Contacts Cohort Team, CAPRISA IMPRESS team, Lung, Humans, Mycobacterium tuberculosis, Tuberculosis, HIV Infections, RNA, Bacterial, Positron-Emission Tomography, Prognosis, Area Under Curve, Sensitivity and Specificity, Cohort Studies, ROC Curve, Adolescent, Point-of-Care Systems, Female, Male, Real-Time Polymerase Chain Reaction, Biomarkers |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Infection, Veterinary and Ecological Sciences |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 10 Jun 2021 09:00 |
| Last Modified: | 18 Jan 2023 22:35 |
| DOI: | 10.1038/s41598-020-65043-8 |
| Open Access URL: | http://doi.org/10.1038/s41598-020-65043-8 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3125837 |
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