Serum biomarkers of treatment response within a randomized clinical trial for pulmonary tuberculosis

Biomarkers 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. We consecutively selected 20 HIV-negative pulmonary TB...

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Bibliographic Details
Published in:Tuberculosis (Edinburgh, Scotland) Vol. 95; no. 4; pp. 415 - 420
Main Authors: Jayakumar, A., Vittinghoff, E., Segal, M.R., MacKenzie, W.R., Johnson, J.L., Gitta, P., Saukkonen, J., Anderson, J., Weiner, M., Engle, M., Yoon, C., Kato-Maeda, M., Nahid, P.
Format: Journal Article
Language:English
Published: Scotland Elsevier Ltd 01.07.2015
Subjects:
Adult
Age Factors
Antitubercular Agents - therapeutic use
Biomarkers
Biomarkers - blood
C-Reactive Protein - metabolism
Cytokines - blood
Enzyme-Linked Immunosorbent Assay
Female
Host-Pathogen Interactions
Humans
Infectious Disease
Logistic Models
Male
Multivariate Analysis
Mycobacterium tuberculosis - drug effects
Mycobacterium tuberculosis - immunology
Mycobacterium tuberculosis - pathogenicity
Predictive Value of Tests
Pulmonary
Pulmonary/Respiratory
Receptors, Cytokine - blood
Receptors, Tumor Necrosis Factor, Type I - blood
Time Factors
Treatment Outcome
Treatment response
Tuberculosis
Tuberculosis, Pulmonary - blood
Tuberculosis, Pulmonary - diagnosis
Tuberculosis, Pulmonary - drug therapy
Tuberculosis, Pulmonary - immunology
Tuberculosis, Pulmonary - microbiology
Uganda
Young Adult
Uganda
Biomarkers
Treatment response
Tuberculosis
Pulmonary
ISSN:1472-9792, 1873-281X, 1873-281X
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Summary:Biomarkers 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. We 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. All but one analyte decreased from baseline to week 8 (all p < 0.01). Individual biomarkers were not associated with 8 week culture status. Logistic models including increasing age, higher baseline soluble tumor necrosis factor receptor alpha 1 (sTNF-R1), and higher week 8 C-reactive protein (CRP) concentration classified subjects by culture status with up to 85% accuracy and acceptable discrimination (cross-validated C-statistic 0.76) and calibration (Hosmer–Lemeshow P > 0.2). Exploratory post-hoc models including sTNF-R1, CRP, and age, classified 8 week culture status with promising accuracy.
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ISSN:1472-9792
1873-281X
1873-281X
DOI:10.1016/j.tube.2015.04.011