Description | ANDRADE, Bruno Bezerril de Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil. 1South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and Division
of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa. 2Center for Infectious
Disease Research, Seattle, WA, USA. 3Brigham and Women’s Hospital, Division of Rheumatology, Immunity and
Inflammation, Harvard Medical School, Boston, USA. 4DST-NRF Centre of Excellence for Biomedical Tuberculosis
Research; South African Medical Research Council Centre for Tuberculosis Research; Division of Molecular Biology
and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
5Max Planck Institute for Infection Biology, Berlin, Germany. 6Hagler Institute for Advanced Study at Texas A&M
University, College Station, TX, USA. 7Catalysis Foundation for Health, San Ramon, CA, USA. 8Desmond Tutu HIV
Centre, and Institute of Infectious Disease and Molecular Medicine (IDM), University of Cape Town, Cape Town,
South Africa. 9Department of Global Health and Social Medicine, and Division of Global Health Equity, Brigham and
Women’s Hospital, Harvard Medical School, Boston, MA, USA. 10Instituto Gonçalo Moniz, Fundação Oswaldo Cruz,
Salvador, Brazil. 11Division of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine,
Nashville, USA. 12Vaccines and Immunity, Medical Research Council Unit, Fajara, The Gambia. 13Centre for the AIDS
Programme of Research in Africa, Durban, South Africa. 14South African Medical Research Council-CAPRISA HIV-TB
Pathogenesis and Treatment Research Unit, Durban, South Africa. 34These authors contributed equally: Adam
Penn-Nicholson, Stanley Kimbung Mbandi, Ethan Thompson and Simon C. Mendelsohn. | pt_BR |
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. | pt_BR |