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Whole-blood PAXgene samples were collected at baseline, month 2 (M2), and end of treatment (EoT). Treatment failure was defined as sputum culture positivity at month 5 or later. Participants were followed for 24\u2009months from treatment initiation for clinical or microbiological tuberculosis recurrence. Unfavorable outcomes were matched \u223c1:3 to recurrence-free cure. Twenty-two published blood transcriptomic signatures were measured by microfluidic RT-qPCR and benchmarked against the WHO Target Product Profile (TPP) criteria.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main results<\/jats:title>\n                    <jats:p>We matched 263 participants with recurrence-free cure to 33 with treatment failure, 24 who died (tuberculosis\/unknown cause), and 9 with recurrence. Signature scores generally declined from baseline to EoT. Multiple signatures measured at baseline and M2 predicted recurrence (AUC range 0.71-0.91), with waning performance when measured at EoT (AUC range 0.42-0.89). Against the WHO TPP, 2\/22 signatures met minimum criteria at baseline, 13\/22 at M2, and none at EoT. Prediction of treatment failure was poor across timepoints (AUC\u2009&amp;lt;\u20090.70). In contrast, several signatures measured at baseline predicted death during treatment or follow-up (AUC\u2009\u2265\u20090.80).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Blood transcriptomic signatures tracked treatment response and predicted recurrence and death, meeting WHO TPP benchmarks at baseline and M2. These findings support prospective, biomarker-guided trials to individualize tuberculosis therapy\u2014shortening regimens for early responders and intensifying care for high-risk patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ajrccm\/aamag156","type":"journal-article","created":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T12:48:25Z","timestamp":1774529305000},"page":"2211-2225","source":"Crossref","is-referenced-by-count":1,"title":["Blood transcriptomic signatures predict poor outcomes in drug-susceptible pulmonary tuberculosis in Brazil"],"prefix":"10.1093","volume":"212","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4054-2766","authenticated-orcid":false,"given":"Simon C","family":"Mendelsohn","sequence":"first","affiliation":[{"name":"South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, Department of Pathology, University of Cape Town , Cape Town,","place":["South 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