Abstract
BackgroundQualitative and quantitative changes in IGRA response offer promise as biomarkers to monitor Tuberculosis (TB) drug therapy, and for the comparison of new interventions. We studied the decay kinetics of TB-specific antigen T-cell responses measured with an in-house ELISPOT assay during the course of therapy.MethodsNewly diagnosed sputum smear positive TB cases with typical TB chest radiographs were recruited. All patients were given standard anti-TB treatment. Each subject was followed up for 6 months and treatment outcomes were documented. Blood samples were obtained for the ESAT-6 and CFP-10 (EC) ELISPOT at diagnosis, 1-, 2-, 4- and 6-months. Qualitative and quantitative reversion of the ELISPOT results were assessed with McNemar test, conditional logistic regression and mixed-effects hierarchical Poisson models.ResultsA total of 116 cases were recruited and EC ELISPOT was positive for 87% (95 of 109) at recruitment. There was a significant decrease in the proportion of EC ELISPOT positive cases over the treatment period (p<0.001). Most of the reversion occurred between the start and first month of treatment and at completion at 6 months. ESAT-6 had higher median counts compared to CFP-10 at all time points. Counts for each antigen declined significantly with therapy (p<0.001). Reverters had lower median SFUs at the start of treatment compared to non-Reverters for both antigens. Apart from the higher median counts for non-Reverters, no other risk factors for non-reversion were found.ConclusionsTB treatment induces qualitative and quantitative reversion of a positive in-house IGRA in newly diagnosed cases of active TB disease. As this does not occur reliably in the majority of cured individuals, qualitative and quantitative reversion of an IGRA ELISPOT has limited clinical utility as a surrogate marker of treatment efficacy.
Highlights
Tuberculosis (TB) is responsible for the greatest number of deaths attributable to a single infectious agent worldwide and most of this mortality is in developing countries.[1]
We have shown that the quantitative response, as measured by ELISPOT, correlates with exposure to a TB case, reflecting the infectious load of M. tuberculosis
Qualitative results over time At recruitment, 95 of 109 cases (87.2%; 95% confidence interval: 79.4–92.8%) with valid results had a positive ESAT-6 and CFP-10 (EC) ELISPOT
Summary
Tuberculosis (TB) is responsible for the greatest number of deaths attributable to a single infectious agent worldwide and most of this mortality is in developing countries.[1] New diagnostic tools, and enhanced treatment strategies, are needed to help combat the TB epidemic. These need to be shown to be useful in TB-endemic tropical settings. Interferon gamma release assays (IGRAs) are utilised in the diagnosis of latent tuberculosis infection (LTBI).[2,3] their performance appears to vary between high burden, resource limited settings and low burden countries.[4] They may have value in the evaluation of new tools against TB. We studied the decay kinetics of TB-specific antigen T-cell responses measured with an in-house ELISPOT assay during the course of therapy
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