Comparing QuantiFERON-TB Gold Plus with Other Tests To Diagnose Mycobacterium tuberculosis Infection.

The fourth-generation QuantiFERON test for tuberculosis infection, QuantiFERON-TB Gold Plus (QFT-Plus) has replaced the earlier version, QuantiFERON-TB Gold In-Tube (QFT-GIT). A clinical need exists for information about agreement between QFT-Plus and other tests. We conducted this study to assess agreement of test results for QFT-Plus with those of QuantiFERON-TB Gold In-Tube (QFT-GIT), T-SPOT.TB (T-SPOT), and the tuberculin skin test (TST). Persons at high risk of latent tuberculosis infection (LTBI) and/or progression to tuberculosis (TB) disease were enrolled at the 10 sites of the Tuberculosis Epidemiologic Studies Consortium from October 2016 through May 2017; each participant received all four tests. Cohen's kappa (κ) and Wilcoxon signed-rank test compared qualitative and quantitative results of QFT-Plus with the other tests. Test results for 506 participants showed 94% agreement between QFT-Plus and QFT-GIT, with 19% positive and 75% negative results. When the tests disagreed, it was most often in the direction of QFT-GIT negative/QFT-Plus positive. QFT-Plus had similar concordance as QFT-GIT with TST (77% and 77%, respectively) and T-SPOT (92% and 91%, respectively). The study showed high agreement between QFT-GIT and QFT-Plus in a direct comparison. Both tests had similar agreement with TST and T-SPOT.

Uncloaking an ancient adversary: Can pathogen biomarker elicitors play a role in confirming extrapulmonary TB and latent TB infection?

Latent tuberculosis infection (LTBI) is diagnosed immunologically using the Mantoux tuberculin skin test (TST) or interferon-gamma release assays (IGRAs). While widely used, immunodiagnostics can produce false negative or false positive results. Pathogen biomarkers provide an alternative, but direct detection in LTBI and extrapulmonary TB cases is challenging. Mycobacterium tuberculosis grows slowly, has limited hematogenous movement, is protected by a lipid rich cell wall, and produces low levels of secreted factors. Here we discuss the potential of elicitors by first considering pathogen markers that may be released following the administration of isoniazid. Isoniazid targets the cell wall of mycobacteria found in extracellular compartments and within monocytes, macrophages, dendritic cells, and lymphatic endothelial cells. Isoniazid's dual-purpose potential as an antibiotic and elicitor is supported by knowledge of latent infection dynamics, time-kill kinetics, and new detection techniques. Within hours, the bactericidal action of isoniazid likely enriches plasma with M. tuberculosis DNA, RNA, proteins/peptides, and lipids. Undoubtedly a portion of these biomarkers are eliminated as some bacilli undergo phagocytosis and lysosomal destruction. However, advances in immunoprecipitation and nucleic acid amplification, combined with the use of larger blood volumes during assay development, may overcome these losses. Other anticipated challenges include determining optimal sample collection times and designing diagnostic workflows that minimize processing-associated marker loss and degradation. Conventional, commercial, and emerging technologies that address these variables are discussed. If realized, isoniazid associated markers could provide proof of concept for novel elicitor-based diagnostic approaches capable of confirming LTBI and empirically treated extrapulmonary TB.