Transcriptomic Signatures of Progression to Tuberculosis Disease Among Close Contacts in Brazil

Abstract Background Approximately 5% of people infected with Mycobacterium tuberculosis progress to tuberculosis (TB) disease without preventive therapy. There is a need for a prognostic test to identify those at highest risk of incident TB so that therapy can be targeted. We evaluated host blood tr...

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Published in:The Journal of infectious diseases Vol. 230; no. 6; pp. e1355 - e1365
Main Authors: Mendelsohn, Simon C, Andrade, Bruno B, Mbandi, Stanley Kimbung, Andrade, Alice M S, Muwanga, Vanessa M, Figueiredo, Marina C, Erasmus, Mzwandile, Rolla, Valeria C, Thami, Prisca K, Cordeiro-Santos, Marcelo, Penn-Nicholson, Adam, Kritski, Afranio L, Hatherill, Mark, Sterling, Timothy R, Scriba, Thomas J
Format: Journal Article
Language:English
Published: US Oxford University Press 16.12.2024
Subjects:
Adolescent
Adult
Brazil - epidemiology
Contact Tracing
Disease Progression
Female
Gene Expression Profiling
Humans
Male
Middle Aged
Mycobacterium tuberculosis - genetics
Prognosis
Transcriptome
Tuberculosis - epidemiology
Tuberculosis - microbiology
Tuberculosis, Pulmonary - blood
Tuberculosis, Pulmonary - epidemiology
Tuberculosis, Pulmonary - microbiology
Young Adult
Brazil
prognostic
transcriptomic
blood
biomarkers
tuberculosis
ISSN:0022-1899, 1537-6613, 1537-6613
Online Access:Get full text
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Summary:Abstract Background Approximately 5% of people infected with Mycobacterium tuberculosis progress to tuberculosis (TB) disease without preventive therapy. There is a need for a prognostic test to identify those at highest risk of incident TB so that therapy can be targeted. We evaluated host blood transcriptomic signatures for progression to TB disease. Methods Close contacts (≥4 hours of exposure per week) of adult patients with culture-confirmed pulmonary TB were enrolled in Brazil. Investigation for incident, microbiologically confirmed, or clinically diagnosed pulmonary or extrapulmonary TB disease through 24 months of follow-up was symptom triggered. Twenty previously validated blood TB transcriptomic signatures were measured at baseline by real-time quantitative polymerase chain reaction. Prognostic performance for incident TB was tested by receiver operating characteristic curve analysis at 6, 9, 12, and 24 months of follow-up. Results Between June 2015 and June 2019, 1854 close contacts were enrolled. Twenty-five progressed to incident TB, of whom 13 had microbiologically confirmed disease. Baseline transcriptomic signature scores were measured in 1789 close contacts. Prognostic performance for all signatures was best within 6 months of diagnosis. Seven signatures (Gliddon4, Suliman4, Roe3, Roe1, Penn-Nicholson6, Francisco2, and Rajan5) met the minimum World Health Organization target product profile for a prognostic test through 6 months and 3 signatures (Gliddon4, Rajan5, and Duffy9) through 9 months. None met the target product profile threshold through ≥12 months of follow-up. Conclusions Blood transcriptomic signatures may be useful for predicting TB risk within 9 months of measurement among TB-exposed contacts to target preventive therapy administration. Host blood transcriptomic signatures predicted progression to incident tuberculosis within 6 to 9 months of measurement among tuberculosis-exposed contacts and may be useful to target preventive therapy to those at greatest risk of progression, reducing unnecessary treatment of those at low risk.
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ISSN:0022-1899
1537-6613
1537-6613
DOI:10.1093/infdis/jiae237