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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Validation of a host blood transcriptomic biomarker for pulmonary tuberculosis in people living with HIV: a prospective diagnostic and prognostic accuracy study
The Lancet Global Health, Volume 9, No. 6, Year 2021
Notification
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Description
Background: A rapid, blood-based triage test that allows targeted investigation for tuberculosis at the point of care could shorten the time to tuberculosis treatment and reduce mortality. We aimed to test the performance of a host blood transcriptomic signature (RISK11) in diagnosing tuberculosis and predicting progression to active pulmonary disease (prognosis) in people with HIV in a community setting. Methods: In this prospective diagnostic and prognostic accuracy study, adults (aged 18–59 years) with HIV were recruited from five communities in South Africa. Individuals with a history of tuberculosis or household exposure to multidrug-resistant tuberculosis within the past 3 years, comorbid risk factors for tuberculosis, or any condition that would interfere with the study were excluded. RISK11 status was assessed at baseline by real-time PCR; participants and study staff were masked to the result. Participants underwent active surveillance for microbiologically confirmed tuberculosis by providing spontaneously expectorated sputum samples at baseline, if symptomatic during 15 months of follow-up, and at 15 months (the end of the study). The coprimary outcomes were the prevalence and cumulative incidence of tuberculosis disease confirmed by a positive Xpert MTB/RIF, Xpert Ultra, or Mycobacteria Growth Indicator Tube culture, or a combination of such, on at least two separate sputum samples collected within any 30-day period. Findings: Between March 22, 2017, and May 15, 2018, 963 participants were assessed for eligibility and 861 were enrolled. Among 820 participants with valid RISK11 results, eight (1%) had prevalent tuberculosis at baseline: seven (2·5%; 95% CI 1·2–5·0) of 285 RISK11-positive participants and one (0·2%; 0·0–1·1) of 535 RISK11-negative participants. The relative risk (RR) of prevalent tuberculosis was 13·1 times (95% CI 2·1–81·6) greater in RISK11-positive participants than in RISK11-negative participants. RISK11 had a diagnostic area under the receiver operating characteristic curve (AUC) of 88·2% (95% CI 77·6–96·7), and a sensitivity of 87·5% (58·3–100·0) and specificity of 65·8% (62·5–69·0) at a predefined score threshold (60%). Of those with RISK11 results, eight had primary endpoint incident tuberculosis during 15 months of follow-up. Tuberculosis incidence was 2·5 per 100 person-years (95% CI 0·7–4·4) in the RISK11-positive group and 0·2 per 100 person-years (0·0–0·5) in the RISK11-negative group. The probability of primary endpoint incident tuberculosis was greater in the RISK11-positive group than in the RISK11-negative group (cumulative incidence ratio 16·0 [95% CI 2·0–129·5]). RISK11 had a prognostic AUC of 80·0% (95% CI 70·6–86·9), and a sensitivity of 88·6% (43·5–98·7) and a specificity of 68·9% (65·3–72·3) for incident tuberculosis at the 60% threshold. Interpretation: RISK11 identified prevalent tuberculosis and predicted risk of progression to incident tuberculosis within 15 months in ambulant people living with HIV. RISK11's performance approached, but did not meet, WHO's target product profile benchmarks for screening and prognostic tests for tuberculosis. Funding: Bill & Melinda Gates Foundation and the South African Medical Research Council. © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC8131200/bin/mmc1.pdf
Authors & Co-Authors
Mendelsohn, Simon C.
South Africa, Cape Town
University of Cape Town
Fioré-Gartland, Andrew J.
United States, Seattle
Fred Hutchinson Cancer Center
Penn-Nicholson, Adam
South Africa, Cape Town
University of Cape Town
Mulenga, Humphrey
South Africa, Cape Town
University of Cape Town
Mbandi, Stanley Kimbung
South Africa, Cape Town
University of Cape Town
Borate, Bhavesh R.
United States, Seattle
Fred Hutchinson Cancer Center
Hadley, Katie E.
South Africa, Cape Town
University of Cape Town
Hikuam, Chris
South Africa, Cape Town
University of Cape Town
Musvosvi, Munyaradzi
South Africa, Cape Town
University of Cape Town
Bilek, Nicole
South Africa, Cape Town
University of Cape Town
Erasmus, Mzwandile
South Africa, Cape Town
University of Cape Town
Jaxa, Lungisa
South Africa, Cape Town
University of Cape Town
Raphela, Rodney
South Africa, Cape Town
University of Cape Town
Nombida, Onke
South Africa, Cape Town
University of Cape Town
Kaskar, Masooda
South Africa, Cape Town
University of Cape Town
Sumner, Tom
United Kingdom, London
London School of Hygiene & Tropical Medicine
White, Richard G.
United Kingdom, London
London School of Hygiene & Tropical Medicine
Innes, Craig
South Africa, Johannesburg
The Aurum Institute
Brumskine, William
South Africa, Johannesburg
The Aurum Institute
Hiemstra, Andriëtte M.
South Africa, Stellenbosch
Stellenbosch University
Malherbe, Stephanus T.
South Africa, Stellenbosch
Stellenbosch University
Hassan-Moosa, Razia
South Africa, Congella
Centre for the Aids Programme of Research in South Africa
South Africa, Tygerberg
South African Medical Research Council
Tameris, Michele D.
South Africa, Cape Town
University of Cape Town
Walzl, Gerhard
South Africa, Stellenbosch
Stellenbosch University
Naidoo, Kogieleum L.
South Africa, Congella
Centre for the Aids Programme of Research in South Africa
South Africa, Tygerberg
South African Medical Research Council
Churchyard, Gavin John
South Africa, Johannesburg
The Aurum Institute
South Africa, Johannesburg
University of the Witwatersrand
Scriba, Thomas Jens
South Africa, Cape Town
University of Cape Town
Hatherill, Mark
South Africa, Cape Town
University of Cape Town
Abrahams, Charmaine
Unknown Affiliation
Africa, Hadn
Unknown Affiliation
Ahlers, Petri
Unknown Affiliation
Arendsen, Denis
Unknown Affiliation
Badimo, Tebogo
Unknown Affiliation
Baepanye, Kagisho
Unknown Affiliation
Baepanye, Kesenogile Edna
Unknown Affiliation
Bande, Bianca
Unknown Affiliation
Batyi, Nomfuneko Cynthia
Unknown Affiliation
Beukes, Roslyn
Unknown Affiliation
Bontsi, Laudicia Tshenolo
Unknown Affiliation
Booi, Obakeng Peter
Unknown Affiliation
Botha, Mari Cathrin
Unknown Affiliation
Braaf, Samentra
Unknown Affiliation
Buhlungu, Sivuyile
Unknown Affiliation
Carstens, Alida
Unknown Affiliation
Chauke, Kgomotso Violet
Unknown Affiliation
Chinappa, Tilagavathy
Unknown Affiliation
Chung, Eva Lisa
Unknown Affiliation
Chung, Michelle
Unknown Affiliation
Clarke, Ken
Unknown Affiliation
Cloete, Yolundi
Unknown Affiliation
Coetzee, Lorraine
Unknown Affiliation
Collignon, Marelize
Unknown Affiliation
Companie, Alessandro
Unknown Affiliation
Corris, Cara Mia
Unknown Affiliation
Cwaile, Mooketsi Theophillius
Unknown Affiliation
Cwele, Thandanani
Unknown Affiliation
Davids, Ilse
Unknown Affiliation
Davies, Isabella Johanna
Unknown Affiliation
de Klerk, Emilia
Unknown Affiliation
de Kock, Marwou
Unknown Affiliation
Dhlamini, Audrey Lebohang
Unknown Affiliation
Diamond, Bongani
Unknown Affiliation
Didloff, Maria
Unknown Affiliation
Dlamini, Celaphiwe
Unknown Affiliation
Dolo, Palesa
Unknown Affiliation
Eyre, Candice
Unknown Affiliation
Feni, Tebogo
Unknown Affiliation
Ferus, Christal
Unknown Affiliation
Fisher, Michelle L.
Unknown Affiliation
Flinn, Marika
Unknown Affiliation
Fransman, Bernadine
Unknown Affiliation
Galane, Welseh Phindile
Unknown Affiliation
Geldenhuys, Hennie D.
Unknown Affiliation
Gempies, Diann
Unknown Affiliation
Goliath, Thelma
Unknown Affiliation
Govender, Dhineshree
Unknown Affiliation
Gregg, Yolande
Unknown Affiliation
Gumede, Goodness Khanyisile
Unknown Affiliation
Gwamada, Zanele
Unknown Affiliation
Halti, Senzo
Unknown Affiliation
Hassiem, Rieyaat
Unknown Affiliation
Herling, Roxane
Unknown Affiliation
Herselman, Yulandi
Unknown Affiliation
Hughes, Ellis
Unknown Affiliation
Issel, Henry
Unknown Affiliation
Iyemosolo, Blanchard Mbay
Unknown Affiliation
Jali, Zandile Patrica
Unknown Affiliation
Janse van Rensburg, Bonita
Unknown Affiliation
Jansen, Ruwiyda
Unknown Affiliation
Jeleni, James Michael
Unknown Affiliation
Jonkane, Olebogeng
Unknown Affiliation
Julies, Fabio
Unknown Affiliation
Kafaar, Fazlin
Unknown Affiliation
Kasongo, Christian Mabika
Unknown Affiliation
Keffers, Sophie
Unknown Affiliation
Kekana, Boitumelo Sophy
Unknown Affiliation
Kekana, Sebaetseng Jeanette
Unknown Affiliation
Kelepu, Xoliswa
Unknown Affiliation
Khanyile, Lungelo
Unknown Affiliation
Khomba, Gloria
Unknown Affiliation
Krüger, Sandra
Unknown Affiliation
Lakhi, Aneessa
Unknown Affiliation
Langa, Nondumiso
Unknown Affiliation
Ledwaba, Hildah
Unknown Affiliation
Leopeng, Thelma
Unknown Affiliation
Louw, Ilze Jeanette
Unknown Affiliation
Luabeya, Angelique Kany Kany
Unknown Affiliation
Mabasa, Immaculate
Unknown Affiliation
Mabuza, Nkosinathi Charles
Unknown Affiliation
Mabwe, Simbarashe
Unknown Affiliation
Majola, Molly
Unknown Affiliation
Makhetha, Mantai
Unknown Affiliation
Makhethe, Lebohang
Unknown Affiliation
Malay, Vernon
Unknown Affiliation
Maphanga, Jabulisiwe Lethabo
Unknown Affiliation
Maphanga, Nonhle Bridgette
Unknown Affiliation
Market, Juanita
Unknown Affiliation
Mbata, Lungile
Unknown Affiliation
Mnqonywa, Nonzwakazi
Unknown Affiliation
Mosito, Boitumelo
Unknown Affiliation
Mosweu, Ireen Lesebang
Unknown Affiliation
Mothaga, Primrose
Unknown Affiliation
Mouton, Angelique Hendricks
Unknown Affiliation
Mthembu, Funeka Nomvula
Unknown Affiliation
Noble, J. Alison
Unknown Affiliation
Ntamo, Bantubonke Bertrum
Unknown Affiliation
Ntshauba, Tedrius
Unknown Affiliation
Opperman, Fajwa
Unknown Affiliation
Padayatchi, Nesri
Unknown Affiliation
Petersen, Christel
Unknown Affiliation
Plaatjie, Patiswa
Unknown Affiliation
Pretorius, Abraham
Unknown Affiliation
Ramjit, Dirhona
Unknown Affiliation
Ratangee, Frances
Unknown Affiliation
Sato, Alicia H.
Unknown Affiliation
Schoeman, Elisma
Unknown Affiliation
Schreuder, Constance
Unknown Affiliation
Seabela, Letlhogonolo
Unknown Affiliation
Selepe, Raesibe Agnes Pearl
Unknown Affiliation
Senne, Melissa Neo
Unknown Affiliation
September, Alison Victoria
Unknown Affiliation
Serake, Moeti G.
Unknown Affiliation
Shenje, Justin Tapiwa
Unknown Affiliation
Shezi, Thandiwe Yvonne
Unknown Affiliation
Stanley, Kim
Unknown Affiliation
Steyn, Marcia
Unknown Affiliation
Swanepoel, Liticia
Unknown Affiliation
Swarts, Anne
Unknown Affiliation
Toefy, Asma
Unknown Affiliation
Tshikovhi, Vincent
Unknown Affiliation
Tswaile, Lebogang Isaac
Unknown Affiliation
Tönsing, Susanne
Unknown Affiliation
van der Merwe, Linda
Unknown Affiliation
van Rooyen, Elma
Unknown Affiliation
Veldsman, Ashley
Unknown Affiliation
Veldtsman, Helen
Unknown Affiliation
Zulu, Mbali Ignatia
Unknown Affiliation
Statistics
Citations: 30
Authors: 157
Affiliations: 8
Identifiers
Doi:
10.1016/S2214-109X(21)00045-0
ISSN:
2214109X
Research Areas
Health System And Policy
Infectious Diseases
Study Design
Cross Sectional Study
Cohort Study
Study Locations
South Africa