Interferon-γ ELISPOT as a Biomarker of Treatment Efficacy in Latent Tuberculosis Infection: A Clinical Trial

Biomarkers that can be used to evaluate new interventions against latent tuberculosis infection (LTBI) and predict reactivation TB disease are urgently required. To evaluate ESAT-6 and CFP-10 (EC) IFN-γ ELISPOT as a biomarker for treatment efficacy in LTBI. This was a randomized, blinded, and placeb...

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Bibliographic Details
Published in:American journal of respiratory and critical care medicine 2013-02, Vol.187 (4), p.439-445
Main Authors: ADETIFA, Ifedayo M, OTA, Martin O. C, BROOKES, Roger H, AKA, Peter, WALTON, Robert, ADEGBOLA, Richard A, HILL, Philip C, JEFFRIES, David J, LUGOS, Moses D, HAMMOND, Abdulrahman S, BATTERSBY, Nicholas J, OWIAFE, Patrick K, DONKOR, Simon D, ANTONIO, Martin, IBANGA, Hannah B
Format: Article
Language:English
Subjects:
Adult
Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy
Antitubercular Agents - therapeutic use
Biological and medical sciences
Biomarkers - blood
Blood. Blood coagulation. Reticuloendothelial system
Double-Blind Method
Enzyme-Linked Immunospot Assay - methods
Enzyme-Linked Immunospot Assay - standards
Female
Gambia
Humans
Intensive care medicine
Interferon-gamma - blood
Interferon-gamma - drug effects
Isoniazid - therapeutic use
Latent Tuberculosis - blood
Latent Tuberculosis - drug therapy
Male
Medical sciences
Mycobacterium tuberculosis - drug effects
Pharmacology. Drug treatments
Treatment Outcome
Young Adult
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Summary:Biomarkers that can be used to evaluate new interventions against latent tuberculosis infection (LTBI) and predict reactivation TB disease are urgently required. To evaluate ESAT-6 and CFP-10 (EC) IFN-γ ELISPOT as a biomarker for treatment efficacy in LTBI. This was a randomized, blinded, and placebo-controlled trial of INH in EC ELISPOT and Mantoux test positive participants. Participants received a 6-month course of 900 mg INH twice weekly or a matching placebo. INH acetylator genotypes were determined and urine tested for INH metabolites to confirm adherence. The proportion of positive responders for CFP-10 and ESAT-6 between treatment arms was compared using mixed effects logistic regression models. A Tweedie (compound Poisson) model was fitted to allow for zero inflation and overdispersion of quantitative response. The proportions of EC ELISPOT-positive subjects reduced over time (P < 0.001) but did not differ by study arm (P = 0.36). Median spot-forming units for ESAT-6 and CFP-10 also declined significantly with time (P < 0.001) but did not differ by study arm (P = 0.74 and 0.71, respectively). There was no evidence of an interaction between acetylator status and INH treatment with respect to ELISPOT results over time. In contacts with LTBI, INH therapy plays no role in observed decreases in Mycobacterium tuberculosis antigen-specific T-cell responses over time. IFN-γ ELISPOT is probably not a useful biomarker of treatment efficacy in LTBI. Clinical trial registered with www.clinicaltrials.gov (NCT 00130325).
ISSN:1073-449X
1535-4970
DOI:10.1164/rccm.201208-1352OC