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.
Keywords. biomarkers; blood; prognostic; transcriptomic; tuberculosis
Clique aqui
- Data de Publicação: 06/05/2024
- Autores: Simon C Mendelsohn , Bruno B Andrade , Stanley Kimbung Mbandi , Alice M S Andrade , Vanessa M Muwanga , Marina C Figueiredo , Mzwandile Erasmus , Valeria C Rolla , Prisca K Thami , Marcelo Cordeiro-Santos , Adam Penn-Nicholson , Afranio L Kritski , Mark Hatherill , Timothy R Sterling , Thomas J Scriba , the RePORT–South Africa and RePORT–Brazil Consortia
