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Publications

Journal Article Observational Study Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Ppublish 13 citations

PubMed: 34520313 DOI: 10.1164/rccm.202103-0548OC

Longitudinal Dynamics of a Blood Transcriptomic Signature of Tuberculosis.

Am J Respir Crit Care Med 204(12):1463-1472

Authors: Humphrey Mulenga, Munyaradzi Musvosvi, Simon C Mendelsohn, Adam Penn-Nicholson, Stanley Kimbung Mbandi, Andrew Fiore-Gartland, Michèle Tameris, Simbarashe Mabwe, Hadn Africa, Nicole Bilek, Fazlin Kafaar, Shabaana A Khader, Balie Carstens, Katie Hadley, Chris Hikuam, Mzwandile Erasmus, Lungisa Jaxa, Rodney Raphela, Onke Nombida, Masooda Kaskar, Mark P Nicol, Slindile Mbhele, Judi Van Heerden, Craig Innes, William Brumskine, Andriëtte Hiemstra, Stephanus T Malherbe, Razia Hassan-Moosa, Gerhard Walzl, Kogieleum Naidoo, Gavin Churchyard, Mark Hatherill, Thomas J Scriba

Affiliations

  • South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, and.
  • Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
  • Department of Molecular Microbiology, Washington University in St. Louis, St. Louis, Missouri.
  • Division of Medical Microbiology, Department of Pathology, University of Cape Town, Cape Town, South Africa.
  • Division of Infection and Immunity, School of Biomedical Sciences, University of Western Australia, Perth, Australia.
  • The Aurum Institute, Johannesburg, Guateng, South Africa.
  • Department of Science and Technology/National Research Foundation Centre of Excellence for Biomedical TB Research and SAMRC Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
  • Centre for the AIDS Programme of Research in South Africa (CAPRISA), Durban, South Africa.
  • Medical Research Council-CAPRISA HIV-Tuberculosis Pathogenesis and Treatment Research Unit, Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa; and.
  • School of Public Health, University of Witwatersrand, Johannesburg, South Africa.

Abstract

Performance of blood transcriptomic tuberculosis (TB) signatures in longitudinal studies and effects of TB-preventive therapy and coinfection with HIV or respiratory organisms on transcriptomic signatures has not been systematically studied. We evaluated longitudinal kinetics of an 11-gene blood transcriptomic TB signature, RISK11, and effects of TB-preventive therapy (TPT) and respiratory organisms on RISK11 signature score, in HIV-uninfected and HIV-infected individuals. RISK11 was measured in a longitudinal study of RISK11-guided TPT in HIV-uninfected adults, a cross-sectional respiratory organisms cohort, or a longitudinal study in people living with HIV (PLHIV). HIV-uninfected RISK11 participants were randomized to TPT or no TPT; RISK11 participants received no TPT. PLHIV received standard-of-care antiretroviral therapy and TPT. In the cross-sectional respiratory organisms cohort, viruses and bacteria in nasopharyngeal and oropharyngeal swabs were quantified by real-time quantitative PCR. RISK11 status was transient in most of the 128 HIV-negative participants with longitudinal samples; more than 70% of RISK11 participants reverted to RISK11 by 3 months, irrespective of TPT. By comparison, reversion from a RISK11 state was less common in 645 PLHIV (42.1%). Non-HIV viral and nontuberculous bacterial organisms were detected in 7.2% and 38.9% of the 1,000 respiratory organisms cohort participants, respectively, and among those investigated for TB, 3.8% had prevalent disease. Median RISK11 scores (%) were higher in participants with viral organisms alone (46.7%), viral and bacterial organisms (42.8%), or prevalent TB (85.7%) than those with bacterial organisms other than TB (13.4%) or no organisms (14.2%). RISK11 could not discriminate between prevalent TB and viral organisms. Positive RISK11 signature status is often transient, possibly due to intercurrent viral infection, highlighting potentially important challenges for implementation of these biomarkers as new tools for TB control.

MeSH

Respiratory Tract Diseases, Respiratory Tract Infections, Bacteria, Tuberculosis, Critical Care, Longitudinal Studies, Blood, Hiv

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