Skip to content
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Four-gene pan-African blood signature predicts progression to tuberculosis
American Journal of Respiratory and Critical Care Medicine, Volume 197, No. 9, Year 2018
Notification
URL copied to clipboard!
Description
Rationale: Contacts of patients with tuberculosis (TB) constitute an important target population for preventive measures because they are at high risk of infection with Mycobacterium tuberculosis and progression to disease. Objectives: We investigated bio-signatures with predictive ability for incident TB. Methods: In a case-control study nested within the Grand Challenges 6-74 longitudinal HIV-negative African cohort of exposed household contacts, we employed RNA sequencing, PCR, and the pair ratio algorithm in a training/test set approach. Overall, 79 progressors who developed TB between 3 and 24 months after diagnosis of index case and 328 matched nonprogressors who remained healthy during 24 months of follow-up were investigated. Measurements and Main Results: A four-transcript signature derived from samples in a South African and Gambian training set predicted progression up to two years before onset of disease in blinded test set samples from South Africa, the Gambia, and Ethiopia with little population-associated variability, and it was also validated in an external cohort of South African adolescents with latent M. tuberculosis infection. By contrast, published diagnostic or prognostic TB signatures were predicted in samples from some but not all three countries, indicating site-specific variability. Post hoc meta-analysis identified a single gene pair, C1QC/TRAV27 (complement C1q C-chain / T-cell receptor-a variable gene 27) that would consistently predict TB progression in household contacts from multiple African sites but not in infected adolescents without known recent exposure events. Conclusions: Collectively, we developed a simple whole blood-based PCR test to predict TB in recently exposed household contacts from diverse African populations. This test has potential for implementation in national TB contact investigation programs. Copyright © 2018 by the American Thoracic Society.
Authors & Co-Authors
Suliman, Sara A.
South Africa, Cape Town
University of Cape Town
Thompson, Ethan G.
United States, Seattle
Seattle Biomedical Research Institute
Sutherland, Jayne S.
Gambia, Serrekunda
Medical Research Council Unit
Weiner, January Mikolaj
Germany, Berlin
Max Planck Institute for Infection Biology
Ota, Martin Okechukwu C.
Gambia, Serrekunda
Medical Research Council Unit
Shankar, Smitha
United States, Seattle
Seattle Biomedical Research Institute
Penn-Nicholson, Adam
South Africa, Cape Town
University of Cape Town
Thiel, Bonnie A.
United States, Cleveland
University Hospitals Case Medical Center
Erasmus, Mzwandile
South Africa, Cape Town
University of Cape Town
Maertzdorf, Jeroen
Germany, Berlin
Max Planck Institute for Infection Biology
Duffy, Fergal J.
United States, Seattle
Seattle Biomedical Research Institute
Hill, Philip C.
New Zealand, Dunedin
University of Otago
Jane Hughes, E.
South Africa, Cape Town
University of Cape Town
Stanley, Kim
South Africa, Stellenbosch
Stellenbosch University
Downing, Katrina J.
South Africa, Cape Town
University of Cape Town
Fisher, Michelle L.
South Africa, Cape Town
University of Cape Town
Valvo, Joe S.
United States, Seattle
Seattle Biomedical Research Institute
Parida, Shreemanta K.
Germany, Berlin
Max Planck Institute for Infection Biology
Van Der Spuy, Gian D.
South Africa, Stellenbosch
Stellenbosch University
Tromp, Gerard C.
South Africa, Stellenbosch
Stellenbosch University
Adetifa, Ifedayo Morayo O.
Gambia, Serrekunda
Medical Research Council Unit
Donkor, Simon A.
Gambia, Serrekunda
Medical Research Council Unit
Howe, Rawleigh Craig
Ethiopia, Addis Ababa
Armauer Hansen Research Institute
Mayanja-Kizza, Harriet
Uganda, Kampala
Makerere University
Henry Boom, W.
United States, Cleveland
University Hospitals Case Medical Center
Dockrell, Hazel M.
United Kingdom, London
London School of Hygiene & Tropical Medicine
Ottenhoff, Tom H.M.
Netherlands, Leiden
Leids Universitair Medisch Centrum
Hatherill, Mark
South Africa, Cape Town
University of Cape Town
Aderem, Alan A.
United States, Seattle
Seattle Biomedical Research Institute
Hanekom, Willem Albert
South Africa, Cape Town
University of Cape Town
Scriba, Thomas J.
South Africa, Cape Town
University of Cape Town
Kaufmann, Stefan Hugo Ernst
Germany, Berlin
Max Planck Institute for Infection Biology
Zak, Daniel E.
United States, Seattle
Seattle Biomedical Research Institute
Walzl, Gerhard
South Africa, Stellenbosch
Stellenbosch University
Black, Gillian Frances
South Africa, Stellenbosch
Stellenbosch University
Kriel, Magdalena
South Africa, Stellenbosch
Stellenbosch University
Du Plessis, Nelita M.
South Africa, Stellenbosch
Stellenbosch University
Nene, Nonhlanhla F.
South Africa, Stellenbosch
Stellenbosch University
Roberts, Teri R.
South Africa, Stellenbosch
Stellenbosch University
Kleynhans, Léanie
South Africa, Stellenbosch
Stellenbosch University
Gutschmidt, Andrea
South Africa, Stellenbosch
Stellenbosch University
Smith, Bronwyn
South Africa, Stellenbosch
Stellenbosch University
Loxton, A. G.
South Africa, Stellenbosch
Stellenbosch University
Chegou, Novel N.
South Africa, Stellenbosch
Stellenbosch University
Tabb, David L.
South Africa, Stellenbosch
Stellenbosch University
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
Joloba, Moses Lutaakome
Uganda, Kampala
Makerere University
Zalwango, Sarah K.
Uganda, Kampala
Makerere University
Nsereko, Mary
Uganda, Kampala
Makerere University
Okwera, Brenda
Uganda, Kampala
Makerere University
Kisingo, Hussein
Uganda, Kampala
Makerere University
Golinski, Robert
Germany, Berlin
Max Planck Institute for Infection Biology
Jacobson, Marc
Germany, Berlin
Max Planck Institute for Infection Biology
Lalor, Maeve K.
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
Lee, Ji-sook
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
Bilek, Nicole
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
Mulenga, Humphrey
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
Kwong Chung, William
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
Geiter, Lawrence J.
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
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
Adegbola, Richard A.
Gambia, Serrekunda
Medical Research Council Unit
Corrah, Tumani P.
Gambia, Serrekunda
Medical Research Council Unit
Antonio, Martin
Gambia, Serrekunda
Medical Research Council Unit
Togun, Toyin Omotayo
Gambia, Serrekunda
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
Kafaar, Fazlin
South Africa, Cape Town
University of Cape Town
Workman, Lesley J.
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
Hussey, Greg Dudley
South Africa, Cape Town
University of Cape Town
Ehrlich, Rodney I.
South Africa, Cape Town
University of Cape Town
Verver, Suzanne
Netherlands, The Hague
Kncv Tuberculosis Foundation
Netherlands, Amsterdam
Amsterdam Umc - University of Amsterdam
Statistics
Citations: 189
Authors: 125
Affiliations: 19
Identifiers
Doi:
10.1164/rccm.201711-2340OC
ISSN:
1073449X
Research Areas
Genetics And Genomics
Infectious Diseases
Study Design
Cross Sectional Study
Cohort Study
Case-Control Study
Study Approach
Systematic review
Study Locations
Ethiopia
Gambia
South Africa