학술논문
Biomarker-guided tuberculosis preventive therapy (CORTIS): a randomised controlled trial
Document Type
Academic Journal
Author
Scriba, Thomas J; Fiore-Gartland, Andrew; Penn-Nicholson, Adam; Mulenga, Humphrey; Kimbung Mbandi, Stanley; Borate, Bhavesh; Mendelsohn, Simon C; Hadley, Katie; Hikuam, Chris; Kaskar, Masooda; Musvosvi, Munyaradzi; Bilek, Nicole; Self, Steven; Sumner, Tom; White, Richard G; Erasmus, Mzwandile; Jaxa, Lungisa; Raphela, Rodney; Innes, Craig; Brumskine, William; Hiemstra, Andriette; Malherbe, Stephanus T; Hassan-Moosa, Razia; Tameris, Michele; Walzl, Gerhard; Naidoo, Kogieleum; Churchyard, Gavin; Hatherill, Mark; Baepanye, Kesenogile; Baepanye, Tshepiso; Clarke, Ken; Collignon, Marelize; Dlamini, Audrey; Eyre, Candice; Feni, Tebogo; Fikizolo, Moogo; Galane, Phinda; Goliath, Thelma; Gangat, Alia; Malefo-Grootboom, Shirley; Janse van Rensburg, Elba; Janse van Rensburg, Bonita; Kekana, Sophy; Zietsman, Marietjie; Kock, Adrianne; Kunene, Israel; Lakhi, Aneessa; Langa, Nondumiso; Ledwaba, Hilda; Luphoko, Marillyn; Mabasa, Immaculate; Mabe, Dorah; Mabuza, Nkosinathi; Majola, Molly; Makhetha, Mantai; Makoanyane, Mpho; Makhubalo, Blossom; Malay, Vernon; Market, Juanita; Matshego, Selvy; Mbipa, Nontsikelelo; Mmotsa, Tsiamo; Modipa, Sylvester; Mopati, Samuel; Moswegu, Palesa; Mothaga, Primrose; Muller, Dorothy; Nchwe, Grace; Nel, Maryna; Nhlangulela, Lindiwe; Ntamo, Bantubonke; Ntoahae, Lawerence; Ntshauba, Tedrius; Sanyaka, Nomsa; Seabela, Letlhogonolo; Selepe, Pearl; Senne, Melissa; Serake, MG; Thlapi, Maria; Tshikovhi, Vincent; Tswaile, Lebogang; van Aswegen, Amanda; Mbata, Lungile; Takavamanya, Constance; Pinho, Pedro; Mdlulu, John; Taljaard, Marthinette; Slabbert, Naydene; Sayed, Sharfuddin; Nielson, Tanya; Ni Sein, Ni; Govender, Dhineshree; Chinappa, Tilagavathy; Zulu, Mbali Ignatia; Maphanga, Nonhle Bridgette; Hlathi, Senzo Ralph; Gumede, Goodness Khanyisile; Shezi, Thandiwe Yvonne; Maphanga, Jabulisiwe Lethabo; Jali, Zandile Patrica; Cwele, Thobelani; Gwamanda, Nonhlanhla Zanele Elsie; Dlamini, Celaphiwe; Sing, Zibuyile Phindile Penlee; Ntanjana, Ntombozuko Gloria; Nzimande, Sphelele Simo; Mbatha, Siyabonga; Maharaj, Bhavna; Moosa, Atika; Corris, Cara-Mia; Kafaar, Fazlin; Geldenhuys, Hennie; Luabeya, Angelique Kany Kany; Shenje, Justin; Botes, Natasja; Rossouw, Susan; Africa, Hadn; Diamond, Bongani; Braaf, Samentra; Stryers, Sonia; Carstens, Alida; Jansen, Ruwiyda; Mabwe, Simbarashe; Herling, Roxane; Veldsman, Ashley; Makhete, Lebohgang; Steyn, Marcia; Buhlungu, Sivuyile; Erasmus, Margareth; Davids, Ilse; Plaatjie, Patiswa; Companie, Alessandro; Ratangee, Frances; Veldtsman, Helen; Petersen, Christel; Abrahams, Charmaine; Moses, Miriam; Kelepu, Xoliswa; Gregg, Yolande; Swanepoel, Liticia; Magawu, Nomsitho; Cetywayo, Nompumelelo; Mactavie, Lauren; Valley, Habibullah; Filander, Elizabeth; Nqakala, Nambitha; Maasdorp, Elizna; Khoury, Justine; Kriel, Belinda; Smith, Bronwyn; Muller, Liesel; Tonsing, Susanne; Loxton, Andre; Ahlers, Petri; Flinn, Marika; Chung, Eva; Chung, Michelle; Sato, Alicia
Source
The Lancet Infectious Diseases. March 2021, Vol. 21 Issue 3, 354
Subject
Language
English
ISSN
1473-3099
Abstract
Summary Background Targeted preventive therapy for individuals at highest risk of incident tuberculosis might impact the epidemic by interrupting transmission. We tested performance of a transcriptomic signature of tuberculosis (RISK11) and efficacy of signature-guided preventive therapy in parallel, using a hybrid three-group study design. Methods Adult volunteers aged 18--59 years were recruited at five geographically distinct communities in South Africa. Whole blood was sampled for RISK11 by quantitative RT-PCR assay from eligible volunteers without HIV, recent previous tuberculosis (ie, Findings 20,207 volunteers were screened, and 2923 participants were enrolled, including RISK11-positive participants randomly assigned to 3HP (n=375) or no 3HP (n=764), and 1784 RISK11-negative participants. Cumulative probability of prevalent or incident tuberculosis disease was 0*066 (95% CI 0*049 to 0*084) in RISK11-positive (3HP negative) participants and 0*018 (0*011 to 0*025) in RISK11-negative participants (RR 3*69, 95% CI 2*25--6*05) over 15 months. Tuberculosis prevalence was 47 (4*1%) of 1139 versus 14 (0*78%) of 1984 in RISK11-positive compared with RISK11-negative participants, respectively (diagnostic RR 5*13, 95% CI 2*93 to 9*43). Tuberculosis incidence over 15 months was 2*09 (95% CI 0*97 to 3*19) vs 0*80 (0*30 to 1*30) per 100 person years in RISK11-positive (3HP-negative) participants compared with RISK11-negative participants (cumulative incidence ratio 2*6, 95% CI 1*2 to 5*9). Serious adverse events related to 3HP included one hospitalisation for seizures (unintentional isoniazid overdose) and one death of unknown cause (possibly temporally related). Tuberculosis incidence over 15 months was 1*94 (95% CI 0*35 to 3*50) versus 2*09 (95% CI 0*97 to 3*19) per 100 person-years in 3HP-treated RISK11-positive participants compared with untreated RISK11-positive participants (efficacy 7*0%, 95% CI -145 to 65). Interpretation The RISK11 signature discriminated between individuals with prevalent tuberculosis, or progression to incident tuberculosis, and individuals who remained healthy, but provision of 3HP to signature-positive individuals after exclusion of baseline disease did not reduce progression to tuberculosis over 15 months. Funding Bill and Melinda Gates Foundation, South African Medical Research Council.