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- Title
Longitudinal Dynamics of a Blood Transcriptomic Signature of Tuberculosis.
- Authors
Mulenga, Humphrey; Musvosvi, Munyaradzi; Mendelsohn, Simon C.; Penn-Nicholson, Adam; Mbandi, Stanley Kimbung; Fiore-Gartland, Andrew; Tameris, Michele; Mabwe, Simbarashe; Africa, Hadn; Bilek, Nicole; Kafaar, Fazlin; Khader, Shabaana A.; Carstens, Balie; Hadley, Katie; Hikuam, Chris; Erasmus, Mzwandile; Jaxa, Lungisa; Raphela, Rodney; Nombida, Onke; Kaskar, Masooda
- Abstract
Rationale: 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. Objectives: 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. Methods: 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. Measurements and Main Results: 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. Conclusions: 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.
- Subjects
TUBERCULOSIS; BIOMARKERS; RESPIRATORY infections; HIV; MESSENGER RNA
- Publication
American Journal of Respiratory & Critical Care Medicine, 2021, Vol 204, Issue 12, p1463
- ISSN
1073-449X
- Publication type
journal article
- DOI
10.1164/rccm.202103-0548OC