{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T13:16:52Z","timestamp":1768569412153,"version":"3.49.0"},"posted":{"date-parts":[[2025,10,8]]},"group-title":"Infectious Diseases (except HIV\/AIDS)","reference-count":58,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T00:00:00Z","timestamp":1759881600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,10,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Non-sputum biomarkers to monitor tuberculosis (TB) treatment and predict poor outcomes are lacking. We evaluated host-blood transcriptomic signatures for treatment monitoring and prognosis (death, treatment failure, recurrence) in adults with pulmonary TB.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Adults with culture-confirmed, drug-susceptible pulmonary TB were enrolled at five Brazilian sites. 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 months from treatment initiation for clinical or microbiological TB recurrence. Unfavourable 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>Results<\/jats:title>\n                  <jats:p>We matched 263 participants with recurrence-free cure to 33 with treatment failure, 24 who died (TB\/unknown cause), and 9 with recurrence. Signature scores generally declined from baseline to EoT. Multiple signatures predicted recurrence at baseline and M2 (AUC range 0.71-0.91), with waning performance 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 &lt;0.70). In contrast, Thompson5 and others at baseline predicted death during treatment or follow-up (AUC \u22650.80).<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusion<\/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 individualise TB therapy\u2014shortening regimens for early responders and intensifying care for high-risk patients.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Funding<\/jats:title>\n                  <jats:p>This work was supported by the U.S. National Institutes of Health, CRDF Global, and Departamento de Ci\u00eancia e Tecnologia (DECIT) - Secretaria de Ci\u00eancia e Tecnologia (SCTIE), Minist\u00e9rio da Sa\u00fade (MS), Brazil.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2025.10.07.25337480","type":"posted-content","created":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T06:10:17Z","timestamp":1759990217000},"source":"Crossref","is-referenced-by-count":0,"title":["Blood transcriptomic signatures predict poor treatment outcomes in drug-susceptible pulmonary TB in Brazil"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4054-2766","authenticated-orcid":false,"given":"Simon C","family":"Mendelsohn","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bruno B","family":"Andrade","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariana","family":"Ara\u00fajo-Pereira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gustavo C","family":"Amorim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mzwandile","family":"Erasmus","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alice MS","family":"Andrade","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michelle","family":"Fisher","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marina C","family":"Figueiredo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vanessa M","family":"Muwanga","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Afranio L","family":"Kritski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcelo","family":"Cordeiro-Santos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valeria C","family":"Rolla","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark","family":"Hatherill","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timothy R","family":"Sterling","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0641-1359","authenticated-orcid":false,"given":"Thomas J","family":"Scriba","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"the RePORT South Africa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"RePORT-Brazil Consortia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2025101106100559000_2025.10.07.25337480v1.1","unstructured":"WHO. 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