ReviewInterferon gamma release assays for monitoring the response to treatment for tuberculosis: A systematic review
Introduction
A biomarker to indicate successful tuberculosis (TB) treatment would be a major advance for the management and control of TB globally. In addition to monitoring treatment in individual patients, it would enable the assessment of shorter course regimens for the treatment of both latent TB infection (LTBI) and active TB; currently the absence of a reliable surrogate marker of cure hampers trials of new TB therapies. Biomarkers to confirm adequate TB treatment would also help reduce transmission from subsequent reactivation following failed treatment. Recent research has focused on the use of interferon gamma (IFN-γ) release assays (IGRAs) as a biomarker of treatment success. Animal and human studies have shown a relationship between the Mycobacterium tuberculosis (MTB) bacillary load and the magnitude of IFN-γ responses to MTB antigens [1], [2]. It has therefore been postulated that a decrease in the magnitude of IFN-γ responses to MTB-specific peptides measured by IGRA can be used as a biomarker of cure [3]. To assess the utility of IGRAs for this purpose, a number of studies have investigated the kinetics of IGRA responses during the treatment of TB. We did a systematic review of the use of IGRAs in monitoring the response to treatment of LTBI or active TB.
Section snippets
Search strategy
Our review was done in accordance with the ‘preferred reporting items for systematic reviews and meta-analyses’ (PRISMA) statement. Original articles, letters to the editor and published abstracts were identified by searching MEDLINE (1995 to November 2014), EMBASE (to November 2014) and the Cochrane Central Register of Controlled Trials (CENTRALL). The following search terms were used:
(tuberculosis/or latent tuberculosis/or lung tuberculosis/) and (gamma interferon/or enzyme linked immunospot
Results
A total of 1508 unique references were identified by the initial search. After review of title and abstracts, 75 full text articles were assessed for eligibility. Forty-five articles were excluded after review of the full texts. Of these 45 articles, 14 used an in-house ELISPOT [1], [2], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15], five were excluded because they did not use ESAT-6/CFP-10-specific stimulation [16], [17], [18], [19], [20], 4 were cross-sectional [21], [22],
Discussion
To our knowledge, this is the largest systematic review evaluating serial IGRA as a potential tool to monitor treatment in patients with active TB and LTBI. Our systematic review includes nine new studies published subsequent to a previous systematic review by Chiappini et al. (which included a total of 13 studies) [77], as well as several earlier studies not included in their review. This is the first review to address quantitative changes in IFN-γ response in addition to qualitative
Funding
None.
Competing interests
The authors do not have a commercial or other association that might pose a conflict of interest.
Ethical approval
Not required.
Authors' contributions
VC and YH did the literature search. VC, YH and CZ selected the studies for analysis. VC wrote the first draft of the manuscript. YH, CZ, TC and NC assisted with data interpretation, data analysis and writing of the manuscript and figures.
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Dynamic changes of interferon gamma release assay results with latent tuberculosis infection treatment
2020, Clinical Microbiology and InfectionCitation Excerpt :On the basis of the hypothesis that the number of effector T cells falls as Mycobacterium tuberculosis (MTB) load declines in response to the treatment, reversion of interferon gamma release assay (IGRA) or decreased number of cells releasing interferon gamma (IFN-γ) was thought to reflect host responses to anti-TB treatment [3]. However, previous findings on the effect of LTBI preventive treatment were heterogeneous [4–9]. Adetifa et al. [8] demonstrated that the proportions of ELISPOT (enzyme-linked immunospot)-positive results and median spot-forming units for ESAT-6 (6 kDa early secretory antigenic target produced by M. tuberculosis) and CFP-10 (10 kDa secreted antigen from M. tuberculosis) declined significantly with time in treatment and placebo groups, indicating that ELISPOT was probably not a useful method for LTBI treatment evaluation.
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The first two authors have contributed equally and wish to be regarded as joint first authors.