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Original Research: Chest Infections |

Effect of Isoniazid Therapy for Latent TB Infection on QuantiFERON-TB Gold In-Tube Responses in Adults With Positive Tuberculin Skin Test Results in a High TB Incidence AreaEffect of Isoniazid Therapy in Latent TB Infection: A Controlled Study

John L. Johnson, MD; Hendrik Geldenhuys, MBChB; Bonnie A. Thiel, MS; Asma Toefy, BSc; Sara Suliman, PhD; Bernadette Pienaar, RN; Phalkun Chheng, MD; Thomas Scriba, PhD; W. Henry Boom, MD; Willem Hanekom, FCPaed; Mark Hatherill, FCPaed
Author and Funding Information

From the Tuberculosis Research Unit (Drs Johnson, Chheng, and Boom and Ms Thiel), Department of Medicine, Case Western Reserve University School of Medicine, and University Hospitals Case Medical Center, Cleveland, OH; and South African Tuberculosis Vaccine Initiative (Drs Geldenhuys, Suliman, Scriba, Hanekom, and Hatherill and Mss Toefy and Pienaar), Institute of Infectious Disease & Molecular Medicine and School of Child and Adolescent Health, University of Cape Town, Cape Town, South Africa.

Correspondence to: John L. Johnson, MD, Tuberculosis Research Unit, Department of Medicine, Case Western Reserve University School of Medicine, 2109 Adelbert Rd, Cleveland, OH 44106-4984; e-mail: jlj@case.edu


Funding/Support: This work was supported by the Tuberculosis Research Unit, Case Western Reserve University, established with funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, and Department of Health and Human Services [N01-AI-95383 and HHSN266200700022C/N01-AI-70022].

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2014;145(3):612-617. doi:10.1378/chest.13-1232
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Background:  T-cell interferon-γ release assays (IGRAs) are used in the diagnosis of Mycobacterium tuberculosis infection and could be useful biomarkers of response to treatment of latent TB infection for clinical trials, infection control units, and TB programs.

Methods:  This investigation was a prospective, controlled substudy of IGRA responses in 82 healthy South African adults with HIV seronegative and positive tuberculin skin test results randomly assigned to treatment with 6 months of daily isoniazid preventive therapy (IPT) or observation before Bacillus Calmette-Guérin revaccination in a clinical trial. QuantiFERON-TB Gold In-Tube (QFT-GIT) assay was used to measure interferon-γ (IFN-γ) response to mycobacterial antigens at baseline and after IPT or observation.

Results:  IFN-γ levels declined between baseline and the end of IPT (signed rank test P ≤ .0001) and between baseline and a similar period of observation without IPT (signed rank test P = .03). The rate of decrease in IFN-γ responses over time did not differ between the groups (Mann-Whitney-Wilcoxon test P = .31). QFT-GIT test results in two subjects (5%) in the IPT group and two subjects (5%) in the observation group reverted from positive to negative during follow-up. No significant difference was found between the groups with respect to baseline positivity or the proportion of patients whose tests reverted to negative.

Conclusions:  IPT had no effect on changes in QFT-GIT readouts during short-term follow-up of adults with positive tuberculin skin tests in a high TB incidence setting. QFT-GIT is unlikely to be a useful biomarker of response to treatment of latent TB infection.

Trial registry:  ClinicalTrials.gov; No.: NCT01119521; URL: www.clinicaltrials.gov

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