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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
general
RISK6, a 6-gene transcriptomic signature of TB disease risk, diagnosis and treatment response
Scientific Reports, Volume 10, No. 1, Article 8629, Year 2020
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Description
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. © 2020, The Author(s).
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC7248089/bin/41598_2020_65043_MOESM1_ESM.docx
https://efashare.b-cdn.net/share/pmc/articles/PMC7248089/bin/41598_2020_65043_MOESM2_ESM.xlsx
Authors & Co-Authors
Penn-Nicholson, Adam
South Africa, Cape Town
University of Cape Town
Mbandi, Stanley Kimbung
South Africa, Cape Town
University of Cape Town
Thompson, Ethan G.
United States, Seattle
Seattle Biomedical Research Institute
Mendelsohn, Simon C.
South Africa, Cape Town
University of Cape Town
Suliman, Sara A.
South Africa, Cape Town
University of Cape Town
United States, Boston
Brigham and Women's Hospital
Chegou, Novel N.
South Africa, Tygerberg
South African Medical Research Council
Malherbe, Stephanus T.
South Africa, Tygerberg
South African Medical Research Council
Darboe, Fatoumatta
South Africa, Cape Town
University of Cape Town
Erasmus, Mzwandile
South Africa, Cape Town
University of Cape Town
Hanekom, Willem A.
South Africa, Cape Town
University of Cape Town
Bilek, Nicole
South Africa, Cape Town
University of Cape Town
Fisher, Michelle L.
South Africa, Cape Town
University of Cape Town
Kaufmann, Stefan H.E.
Germany, Berlin
Max Planck Institute for Infection Biology
United States, College Station
Texas A&m University
Winter, Jill
United States, San Ramon
Catalysis Foundation for Health
Murphy, Melissa
South Africa, Cape Town
University of Cape Town
Wood, Robin R.
South Africa, Cape Town
Desmond Tutu Health Foundation
Morrow, Carl D.
South Africa, Cape Town
Desmond Tutu Health Foundation
Van Rhijn, Ildiko
United States, Boston
Brigham and Women's Hospital
Moody, Branch
United States, Boston
Brigham and Women's Hospital
Murray, Megan B.
United States, Boston
Brigham and Women's Hospital
Andrade, Bruno B.
Brazil, Rio de Janeiro
Fundacao Oswaldo Cruz
Sterling, Timothy R.
United States, Nashville
Vanderbilt University School of Medicine
Sutherland, Jayne S.
Gambia, Fajara
Medical Research Council Unit
Naidoo, Kogieleum L.
South Africa, Congella
Centre for the Aids Programme of Research in South Africa
Padayatchi, Nesri
South Africa, Congella
Centre for the Aids Programme of Research in South Africa
Walzl, Gerhard
South Africa, Tygerberg
South African Medical Research Council
Hatherill, Mark
South Africa, Cape Town
University of Cape Town
Zak, Daniel E.
United States, Seattle
Seattle Biomedical Research Institute
Scriba, Thomas Jens
South Africa, Cape Town
University of Cape Town
Kafaar, Fazlin
South Africa, Cape Town
University of Cape Town
Workman, Lesley J.
South Africa, Cape Town
University of Cape Town
Mulenga, Humphrey
South Africa, Cape Town
University of Cape Town
Hughes, Elizabeth Jane
South Africa, Cape Town
University of Cape Town
Xasa, Onke
South Africa, Cape Town
University of Cape Town
Veldsman, Ashley
South Africa, Cape Town
University of Cape Town
Cloete, Yolundi
South Africa, Cape Town
University of Cape Town
Abrahams, Deborah Ann
South Africa, Cape Town
University of Cape Town
Moyo, Sizulu
South Africa, Cape Town
University of Cape Town
Gelderbloem, Sebastian J.
South Africa, Cape Town
University of Cape Town
Tameris, Michele D.
South Africa, Cape Town
University of Cape Town
Geldenhuys, Hennie D.
South Africa, Cape Town
University of Cape Town
Ehrlich, Rodney I.
South Africa, Cape Town
University of Cape Town
Verver, Suzanne
Netherlands, Amsterdam
Amsterdam Umc - University of Amsterdam
Geiter, Lawrence J.
United States, Rockville
Aeras
Black, Gillian Frances
South Africa, Tygerberg
South African Medical Research Council
Van Der Spuy, Gian D.
South Africa, Tygerberg
South African Medical Research Council
Stanley, Kim
South Africa, Tygerberg
South African Medical Research Council
Kriel, Magdalena
South Africa, Tygerberg
South African Medical Research Council
Du Plessis, Nelita M.
South Africa, Tygerberg
South African Medical Research Council
Nene, Nonhlanhla F.
South Africa, Tygerberg
South African Medical Research Council
Roberts, Teri R.
South Africa, Tygerberg
South African Medical Research Council
Kleynhans, Léanie
South Africa, Tygerberg
South African Medical Research Council
Gutschmidt, Andrea
South Africa, Tygerberg
South African Medical Research Council
Smith, Bronwyn
South Africa, Tygerberg
South African Medical Research Council
Loxton, A. G.
South Africa, Tygerberg
South African Medical Research Council
Tromp, Gerard C.
South Africa, Tygerberg
South African Medical Research Council
Tabb, David L.
South Africa, Tygerberg
South African Medical Research Council
Ottenhoff, Tom Henricus Maria
Netherlands, Leiden
Leids Universitair Medisch Centrum
Klein, Michèl R.
Netherlands, Leiden
Leids Universitair Medisch Centrum
Haks, Mariëlle C.
Netherlands, Leiden
Leids Universitair Medisch Centrum
Franken, Kees L.M.C.
Netherlands, Leiden
Leids Universitair Medisch Centrum
Geluk, Annemieke
Netherlands, Leiden
Leids Universitair Medisch Centrum
van Meijgaarden, Krista E.
Netherlands, Leiden
Leids Universitair Medisch Centrum
Joosten, Simone A.
Netherlands, Leiden
Leids Universitair Medisch Centrum
Boom, W. Henry
United States, Cleveland
University Hospitals Case Medical Center
Thiel, Bonnie A.
United States, Cleveland
University Hospitals Case Medical Center
Mayanja-Kizza, Harriet
Uganda, Kampala
Makerere University College of Health Sciences
Joloba, Moses Lutaakome
Uganda, Kampala
Makerere University College of Health Sciences
Zalwango, Sarah K.
Uganda, Kampala
Makerere University College of Health Sciences
Nsereko, Mary
Uganda, Kampala
Makerere University College of Health Sciences
Okwera, Brenda
Uganda, Kampala
Makerere University College of Health Sciences
Kisingo, Hussein
Uganda, Kampala
Makerere University College of Health Sciences
Parida, Shreemanta K.
Germany, Berlin
Max Planck Institute for Infection Biology
Golinski, Robert
Germany, Berlin
Max Planck Institute for Infection Biology
Maertzdorf, Jeroen
Germany, Berlin
Max Planck Institute for Infection Biology
Weiner, January Mikolaj
Germany, Berlin
Max Planck Institute for Infection Biology
Jacobson, Marc
Germany, Berlin
Max Planck Institute for Infection Biology
Dockrell, Hazel M.
United Kingdom, London
London School of Hygiene & Tropical Medicine
Smith, Steven G.
United Kingdom, London
London School of Hygiene & Tropical Medicine
Gorak-Stolinska, Patricia M.A.
United Kingdom, London
London School of Hygiene & Tropical Medicine
Hur, Yun-gyoung
United Kingdom, London
London School of Hygiene & Tropical Medicine
Lalor, Maeve K.
United Kingdom, London
London School of Hygiene & Tropical Medicine
Lee, Jisook
United Kingdom, London
London School of Hygiene & Tropical Medicine
Crampin, Amelia Catharine
Malawi, Chilumba
Malawi Epidemiology and Intervention Research Unit
French, N.
Malawi, Chilumba
Malawi Epidemiology and Intervention Research Unit
Ngwira, Bagrey M.M.
Malawi, Chilumba
Malawi Epidemiology and Intervention Research Unit
Ben-Smith, Anne W.
Malawi, Chilumba
Malawi Epidemiology and Intervention Research Unit
Watkins, Kate
Malawi, Chilumba
Malawi Epidemiology and Intervention Research Unit
Ambrose, Lyn R.
Malawi, Chilumba
Malawi Epidemiology and Intervention Research Unit
Simukonda, Felanji D.
Malawi, Chilumba
Malawi Epidemiology and Intervention Research Unit
Mvula, Hazzie
Malawi, Chilumba
Malawi Epidemiology and Intervention Research Unit
Chilongo, Femia
Malawi, Chilumba
Malawi Epidemiology and Intervention Research Unit
Saul, Jacky
Malawi, Chilumba
Malawi Epidemiology and Intervention Research Unit
Branson, Keith
Malawi, Chilumba
Malawi Epidemiology and Intervention Research Unit
Mahomed, Hassan
South Africa, Cape Town
University of Cape Town
Downing, Katrina J.
South Africa, Cape Town
University of Cape Town
Abel, Brian
South Africa, Cape Town
University of Cape Town
Bowmaker, Mark
South Africa, Cape Town
University of Cape Town
M Kagina, Benjamin Mugo N.
South Africa, Cape Town
University of Cape Town
Chung, William Kwong
South Africa, Cape Town
University of Cape Town
Sadoff, Jerald C.
United States, Rockville
Aeras
Sizemore, Donata R.
United States, Rockville
Aeras
Ramachandran, S.
United States, Rockville
Aeras
Barker, Lew F.
United States, Rockville
Aeras
Brennan, Michael James
United States, Rockville
Aeras
Weichold, Frank F.
United States, Rockville
Aeras
Muller, Stefanie
United States, Rockville
Aeras
Kassa, Desta
Ethiopia, Addis Ababa
Ethiopian Public Health Institute
Abebe, Almaz
Ethiopia, Addis Ababa
Ethiopian Public Health Institute
Mesele, Tsehayenesh
Ethiopia, Addis Ababa
Ethiopian Public Health Institute
Tegbaru, Belete
Ethiopia, Addis Ababa
Ethiopian Public Health Institute
van Baarle, Debbie
Netherlands, Utrecht
University Medical Center Utrecht
Miedema, Frank F.
Netherlands, Utrecht
University Medical Center Utrecht
Howe, Rawleigh Craig
Ethiopia, Addis Ababa
Armauer Hansen Research Institute
Mihret, Adane
Ethiopia, Addis Ababa
Armauer Hansen Research Institute
Aseffa, Abraham
Ethiopia, Addis Ababa
Armauer Hansen Research Institute
Bekele, Yonas Y.
Ethiopia, Addis Ababa
Armauer Hansen Research Institute
Iwnetu, Rachel
Ethiopia, Addis Ababa
Armauer Hansen Research Institute
Tafesse, Mesfin
Ethiopia, Addis Ababa
Armauer Hansen Research Institute
Yamuah, Lawrence K.
Ethiopia, Addis Ababa
Armauer Hansen Research Institute
Ota, Martin Okechukwu C.
Gambia, Fajara
Medical Research Council Unit
Hill, Philip C.
Gambia, Fajara
Medical Research Council Unit
Adegbola, Richard A.
Gambia, Fajara
Medical Research Council Unit
Corrah, Tumani P.
Gambia, Fajara
Medical Research Council Unit
Antonio, Martin
Gambia, Fajara
Medical Research Council Unit
Togun, Toyin Omotayo
Gambia, Fajara
Medical Research Council Unit
Adetifa, Ifedayo
Gambia, Fajara
Medical Research Council Unit
Donkor, Simon A.
Gambia, Fajara
Medical Research Council Unit
Andersen, Peter Lawætz
Denmark, Copenhagen
Statens Serum Institut
Rosenkrands, Ida
Denmark, Copenhagen
Statens Serum Institut
Doherty, Timothy Mark
Denmark, Copenhagen
Statens Serum Institut
Weldingh, Karin N.
Denmark, Copenhagen
Statens Serum Institut
Schoolnik, Gary K.
United States, Palo Alto
Stanford University
Dolganov, Gregory M.
United States, Palo Alto
Stanford University
Van, Tran T.
United States, Palo Alto
Stanford University
Arendsen, Denis
South Africa, Cape Town
University of Cape Town
Africa, Hadn
South Africa, Cape Town
University of Cape Town
Baartman, Veronica
South Africa, Cape Town
University of Cape Town
Filander, Elizabeth
South Africa, Cape Town
University of Cape Town
Mabwe, Simbarashe
South Africa, Cape Town
University of Cape Town
Makhethe, Lebohang
South Africa, Cape Town
University of Cape Town
van Rooyen, Michele
South Africa, Cape Town
University of Cape Town
Steyn, Marcia
South Africa, Cape Town
University of Cape Town
Ahlers, Petri
South Africa, Tygerberg
South African Medical Research Council
van Rensburg, Ilana C.
South Africa, Tygerberg
South African Medical Research Council
Mutavhatsindi, Hygon
South Africa, Tygerberg
South African Medical Research Council
Manngo, Portia M.
South Africa, Tygerberg
South African Medical Research Council
Hiemstra, Andriëtte M.
South Africa, Tygerberg
South African Medical Research Council
McAnda, Shirley P.
South Africa, Tygerberg
South African Medical Research Council
Mendy, Joseph F.
Gambia, Fajara
Medical Research Council Unit
Gindeh, Awa
Gambia, Fajara
Medical Research Council Unit
Mbayo, Georgetta
Gambia, Fajara
Medical Research Council Unit
Owolabi, Olumuyiwa A.
Gambia, Fajara
Medical Research Council Unit
Ayalew, Sosina
Ethiopia, Addis Ababa
Armauer Hansen Research Institute
Tessema, Bamlak
Ethiopia, Addis Ababa
Armauer Hansen Research Institute
Nepolo, Emmanuel
Namibia, Windhoek
University of Namibia
Sheehama, Jacob Angara
Namibia, Windhoek
University of Namibia
Günther, Gunar
Namibia, Windhoek
University of Namibia
Diergaardt, Azaria
Namibia, Windhoek
University of Namibia
Ottenhoff, Tom H.M.
Netherlands, Leiden
Leids Universitair Medisch Centrum
Corstjens, Paul L.A.M.
Netherlands, Leiden
Leids Universitair Medisch Centrum
Kriel, Belinda A.
South Africa, Tygerberg
South African Medical Research Council
Kotzé, Leigh Ann
South Africa, Tygerberg
South African Medical Research Council
Awoniyi, Dolapo Olaitan
South Africa, Tygerberg
South African Medical Research Council
Maasdorp, Elizna
South Africa, Tygerberg
South African Medical Research Council
Sillah, Abdou K.
Gambia, Fajara
Medical Research Council Unit
Namuganga, Anna Ritah
Uganda, Kampala
Makerere University College of Health Sciences
Muzanyi, Grace
Uganda, Kampala
Makerere University College of Health Sciences
Peters, Pierre A.S.
Uganda, Kampala
Makerere University College of Health Sciences
van der Vyver, Marieta
Namibia, Windhoek
University of Namibia
Amutenya, Faustina N.
Namibia, Windhoek
University of Namibia
Nelongo, Josefina N.
Namibia, Windhoek
University of Namibia
Monye, Lidia
Namibia, Windhoek
University of Namibia
Iipinge, Scholastica
Namibia, Windhoek
University of Namibia
Amberbir, Alemayehu
Malawi, Chilumba
Malawi Epidemiology and Intervention Research Unit
Houben, Rein M.G.J.
Malawi, Chilumba
Malawi Epidemiology and Intervention Research Unit
Gebrezgeabher, Atsbeha
Ethiopia, Addis Ababa
Ethiopian Public Health Institute
Mesfin, Getnet
Ethiopia, Addis Ababa
Ethiopian Public Health Institute
Belay, Yohannes
Ethiopia, Addis Ababa
Ethiopian Public Health Institute
Gebremicael, Gebremedhin
Ethiopia, Addis Ababa
Ethiopian Public Health Institute
Alemayehu, Yodit
Ethiopia, Addis Ababa
Ethiopian Public Health Institute
Corstjens, Paul L.A.M.
Netherlands, Leiden
Leids Universitair Medisch Centrum
de Dood, Claudia J.
Netherlands, Leiden
Leids Universitair Medisch Centrum
van der Ploeg-van Schip, Jolien J.
Netherlands, Leiden
Leids Universitair Medisch Centrum
Aagaard, Claus Sindbjerg
Denmark, Copenhagen
Statens Serum Institut
Esterhuyse, Maria M.
Germany, Berlin
Max Planck Institute for Infection Biology
Cliff, Jacqueline Margaret
United Kingdom, London
London School of Hygiene & Tropical Medicine
Cubillos-Angulo, Juan Manuel
Brazil, Rio de Janeiro
Fundacao Oswaldo Cruz
Fukutani, Kiyoshi Ferreira
Brazil, Rio de Janeiro
Fundacao Oswaldo Cruz
Khouri, Ricardo
Brazil, Rio de Janeiro
Fundacao Oswaldo Cruz
Queiroz, Artur T. L.
Brazil, Rio de Janeiro
Fundacao Oswaldo Cruz
Cavalcanti Rolla, Valéria Cavalcanti
Brazil, Rio de Janeiro
Instituto Nacional de Infectologia Evandro Chagas Ini
Durovni, Betina
Brazil, Sao Paulo
Secretaria de Estado da Saude de Sao Paulo
Cordeiro-Santos, Marcelo
Brazil, Manaus
Fundação de Medicina Tropical Doutor Heitor Vieira Dourado
Kritski, Afrânio Lineu
Brazil, Rio de Janeiro
Universidade Federal do Rio de Janeiro
Lapa-e-Silva, José Roberto
Brazil, Rio de Janeiro
Universidade Federal do Rio de Janeiro
Figueiredo, Marina Cruvinel
United States, Nashville
Vanderbilt University School of Medicine
Tamara, Kattya Lopez
United States, Boston
Brigham and Women's Hospital
Peru, Lima
Socios en Salud Lima
Segundo Ramos, Leon Sandoval
Peru, Lima
Socios en Salud Lima
Govender, Dhineshree
South Africa, Congella
Centre for the Aids Programme of Research in South Africa
Hassan-Moosa, Razia
South Africa, Congella
Centre for the Aids Programme of Research in South Africa
Naidoo, Anushka
South Africa, Congella
Centre for the Aids Programme of Research in South Africa
Adams, Rochelle Nicola
South Africa, Congella
Centre for the Aids Programme of Research in South Africa
Samsunder, Natasha
South Africa, Congella
Centre for the Aids Programme of Research in South Africa
Lewis, Lara
South Africa, Congella
Centre for the Aids Programme of Research in South Africa
Statistics
Citations: 71
Authors: 205
Affiliations: 30
Identifiers
Doi:
10.1038/s41598-020-65043-8
ISSN:
20452322
Research Areas
Disability
Environmental
Genetics And Genomics
Infectious Diseases
Study Design
Cohort Study
Study Approach
Quantitative