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

被引：42

作者：

Adetifa, Ifedayo M. ^{[1
]}

Ota, Martin O. C. ^{[1
]}

Jeffries, David J. ^{[1
]}

Lugos, Moses D. ^{[1
]}

Hammond, Abdulrahman S. ^{[1
]}

Battersby, Nicholas J. ^{[1
]}

Owiafe, Patrick K. ^{[1
]}

Donkor, Simon D. ^{[1
]}

Antonio, Martin ^{[1
]}

Ibanga, Hannah B. ^{[1
]}

Brookes, Roger H. ^{[1
]}

Aka, Peter ^{[1
]}

Walton, Robert ^{[1
]}

Adegbola, Richard A. ^{[1
]}

Hill, Philip C. ^{[2
]}

机构：

[1] MRC Unit, Fajara, Gambia

[2] Univ Otago, Sch Med, Dept Prevent & Social Med, Ctr Int Hlth, Dunedin, New Zealand

来源：

AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE | 2013年 / 187卷 / 04期

基金：

英国医学研究理事会;

关键词：

latent tuberculosis infection; isoniazid; IFN-gamma release assays; clinical trial; ELISPOT reversion; LINKED IMMUNOSPOT ASSAY; T-CELL RESPONSES; MYCOBACTERIUM-TUBERCULOSIS; RELEASE ASSAYS; SKIN-TEST; ARKANSAS METHOD; DIAGNOSIS; RELEVANCE; CHILDREN; AREAS;

D O I：

10.1164/rccm.201208-1352OC

中图分类号：

R4 [临床医学];

学科分类号：

1002 ; 100602 ;

摘要：

Rationale: Biomarkers that can be used to evaluate new interventions against latent tuberculosis infection (LTBI) and predict reactivation TB disease are urgently required. Objectives: To evaluate ESAT-6 and CFP-10 (EC) IFN-gamma ELISPOT as a biomarker for treatment efficacy in LTBI. Methods: This was a randomized, blinded, and placebo-controlled trial of INH in EC ELISPOT and Mantoux test positive participants. Measurements and Main Results: 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. Conclusions: In contacts with LTBI, INH therapy plays no role in observed decreases in Mycobacterium tuberculosis antigen specific T-cell responses over time. IFN-gamma ELISPOT is probably not a useful biomarker of treatment efficacy in LTBI. Clinical trial registered with www.clinicaltrials.gov (NCT 00130325).

引用

页码：439 / 445

页数：7

共 40 条

[1]

Adegbola RA, 2003, INT J TUBERC LUNG D, V7, P390

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