1. Serum biomarkers of treatment response within a randomized clinical trial for pulmonary tuberculosis
- Author
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Jayakumar, A, Vittinghoff, E, Segal, MR, MacKenzie, WR, Johnson, JL, Gitta, P, Saukkonen, J, Anderson, J, Weiner, M, Engle, M, Yoon, C, Kato-Maeda, M, Nahid, P, and Tuberculosis Trials Consortium
- Subjects
Adult ,Male ,Time Factors ,Clinical Trials and Supportive Activities ,Type I ,Antitubercular Agents ,Enzyme-Linked Immunosorbent Assay ,Treatment response ,Medical and Health Sciences ,Microbiology ,Young Adult ,Rare Diseases ,Predictive Value of Tests ,Clinical Research ,Receptors ,Humans ,Tuberculosis ,Uganda ,Cytokine ,Lung ,Prevention ,Age Factors ,Evaluation of treatments and therapeutic interventions ,Mycobacterium tuberculosis ,Pulmonary ,C-Reactive Protein ,Treatment Outcome ,Logistic Models ,Infectious Diseases ,Good Health and Well Being ,6.1 Pharmaceuticals ,Multivariate Analysis ,Host-Pathogen Interactions ,Cytokines ,Female ,Tuberculosis Trials Consortium ,Tumor Necrosis Factor ,Biomarkers - Abstract
RationaleBiomarkers for monitoring response to anti-tuberculosis treatment are needed. We explored immune markers previously published as having predictive capability for 8 week culture status in 39 adults enrolled in a clinical trial in Kampala, Uganda.MethodsWe consecutively selected 20 HIV-negative pulmonary TB subjects with positive cultures, and 19 subjects with negative cultures at the end of intensive phase therapy. At baseline and after 8 weeks, serum was assayed for nine cytokines and soluble cytokine receptors using multiplexed platforms or ELISA. We evaluated their association with week 8 culture status first using single-variable logistic models, then using cross-validated estimates of the C-statistic, a measure of discrimination, of candidate models including 2 or 3 analytes in addition to age.ResultsAll but one analyte decreased from baseline to week 8 (all p0.2).ConclusionExploratory post-hoc models including sTNF-R1, CRP, and age, classified 8 week culture status with promising accuracy.
- Published
- 2015