{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T02:53:50Z","timestamp":1790650430068,"version":"4.1.0"},"reference-count":21,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2013,2,1]],"date-time":"2013-02-01T00:00:00Z","timestamp":1359676800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>The lack of consistent associations between clinical outcomes and microbiological responses to therapy for some infectious diseases has raised questions about the adequacy of microbiological endpoints for tuberculosis treatment trials.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To evaluate the association between symptoms and microbiological response to tuberculosis treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed a retrospective analysis of four clinical trials in which participants had culture-positive tuberculosis, standardized symptom assessment, and follow-up mycobacterial cultures. Two trials (studies 22 and 23) followed participants to identify recurrent tuberculosis; participants in studies 27 and 28 were only followed to treatment completion.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>This analysis included 1,978 participants; 39 (2.0%) had culture-confirmed treatment failure, and 75 (3.9%) had culture-confirmed recurrence. Productive cough was associated with indices of increased mycobacterial burden at diagnosis (acid-fast smear grade, severity of radiographic abnormalities). Fever and sweats improved rapidly with treatment, whereas productive cough decreased more slowly and was present in 20% of visits after treatment completion. During treatment, study participants with productive cough more often had concurrent culture positivity compared with those without productive cough (studies 22 and 23: adjusted odds ratio, 1.80; 95% confidence interval [CI], 1.33\u20132.44). Finally, symptoms during the latter part of treatment and follow-up were associated with culture-confirmed treatment failure and recurrence in studies 22 and 23 (for cough: adjusted hazard ratio, 2.07; 95% CI, 1.23\u20133.49; for fever: adjusted hazard ratio, 5.05; 95% CI, 2.76\u20139.19).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>There are consistent relationships between symptoms and microbiological indices of tuberculosis, including measures of mycobacterial burden at baseline, culture positivity during treatment, and time to culture-confirmed treatment failure and recurrence.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1513\/annalsats.201207-038oc","type":"journal-article","created":{"date-parts":[[2014,2,14]],"date-time":"2014-02-14T10:04:03Z","timestamp":1392372243000},"page":"18-25","source":"Crossref","is-referenced-by-count":22,"title":["The Association between Symptoms and Microbiologically Defined Response to Tuberculosis Treatment"],"prefix":"10.1093","volume":"10","author":[{"given":"Craig M.","family":"Hales","sequence":"first","affiliation":[{"name":"Division of Tuberculosis Elimination, Centers for Disease Control and Prevention, Atlanta, Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles M.","family":"Heilig","sequence":"additional","affiliation":[{"name":"Division of Tuberculosis Elimination, Centers for Disease Control and Prevention, Atlanta, Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Chaisson","sequence":"additional","affiliation":[{"name":"Johns Hopkins University, Baltimore, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi Chiu","family":"Leung","sequence":"additional","affiliation":[{"name":"Hong Kong Department of Health, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwok Chiu","family":"Chang","sequence":"additional","affiliation":[{"name":"Hong Kong Department of Health, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan V.","family":"Goldberg","sequence":"additional","affiliation":[{"name":"Division of Tuberculosis Elimination, Centers for Disease Control and Prevention, Atlanta, Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fred","family":"Gordin","sequence":"additional","affiliation":[{"name":"Veterans Affairs Medical Center and George Washington University, Washington, DC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John L.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Tuberculosis Research Unit, Department of Medicine, Case Western Reserve University, Cleveland, Ohio; University Hospitals Case Medical Center, Cleveland, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace","family":"Muzanyi","sequence":"additional","affiliation":[{"name":"Uganda-Case Western Reserve University Research Collaboration, Kampala, Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jussi","family":"Saukkonen","sequence":"additional","affiliation":[{"name":"Boston University School of Medicine, Boston, Massachusetts; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Vernon","sequence":"additional","affiliation":[{"name":"Division of Tuberculosis Elimination, Centers for Disease Control and Prevention, Atlanta, Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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