{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T06:21:54Z","timestamp":1787638914162,"version":"build-2736575974"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T00:00:00Z","timestamp":1787616000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Pediatric tuberculosis (TB) is challenging to diagnose and confirm. The World Health Organization has prioritized development of non-sputum-based diagnostics. We investigated the role of plasma K\/T ratio for TB diagnosis among children with and without HIV.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methodology<\/jats:title>\n                    <jats:p>\n                      Plasma tryptophan and kynurenine concentrations measured via enzyme-linked immunosorbent assay (ELISA) were used to calculate K\/T ratios in a nested case-control design with an optimization cohort (the Lung Cohort Study (LCS)) and a validation cohort (the NIH Stool4TB. The discovery cohort included children with incident TB (\n                      <jats:italic>n<\/jats:italic>\n                      = 23) and age- and sex-matched controls (\n                      <jats:italic>n<\/jats:italic>\n                      = 75). The Stool4TB validation cohort included participants with and without HIV who had microbiologically confirmed TB (\n                      <jats:italic>n<\/jats:italic>\n                      = 15) or clinically diagnosed TB (\n                      <jats:italic>n<\/jats:italic>\n                      = 20), and controls (\n                      <jats:italic>n<\/jats:italic>\n                      = 25).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      LCS participants with HIV-associated TB had higher plasma K\/T ratio (median 0.511 [IQR 0.182\u20130.820]) than controls (median 0.053 [IQR 0.030\u20130.072]),\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.0001. Among participants with microbiologically confirmed TB living with HIV, plasma K\/T ratio gave a sensitivity of 95% (CI 79\u201399), specificity of 85% (CI 0.75\u20130.91), PPV of 85%, NPV of 98%, and AUC of 0.96 (95% CI 0.93\u20130.99). In the validation cohort, among HIV uninfected children, applying a cut-off value of 0.090 gave a sensitivity of 83 % (CI 0.43\u20130.99), specificity of 96% (CI 0.80\u20130.99), PPV of 96%, NPV of 90%, and AUC of 0.92 (95% CI 0.82\u20131) for laboratory confirmed TB. In the LCS, participants who had received intermittent preventative therapy had lower K\/T ratio compared to those who did not (\n                      <jats:italic>p<\/jats:italic>\n                      = 0.0191).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Plasma K\/T ratio is a sensitive non-sputum-based test for diagnosing TB in children and has promising application within pediatric TB diagnostic algorithms.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmicb.2026.1898324","type":"journal-article","created":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T05:35:24Z","timestamp":1787636124000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Plasma kynurenine\/tryptophan ratio as a sensitive blood-based diagnostic tool for tuberculosis: a diagnostic accuracy 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