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Halliday A, Jain P, Hoang L, et al. New technologies for diagnosing active TB: the VANTDET diagnostic accuracy study. Southampton (UK): NIHR Journals Library; 2021 Apr. (Efficacy and Mechanism Evaluation, No. 8.5.)

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New technologies for diagnosing active TB: the VANTDET diagnostic accuracy study.

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Appendix 15Additional data for the validation of candidate rule-out tests

FIGURE 30. Relative abundance of (a) CXCL10, (b) CXCL9, (c) IFNγ and (d) BATF2 in key patient groups within the GO/NO-GO cohort for assessment of the candidate molecular rule-out test.
FIGURE 30. Relative abundance of (a) CXCL10, (b) CXCL9, (c) IFNγ and (d) BATF2 in key patient groups within the GO/NO-GO cohort for assessment of the candidate molecular rule-out test.
FIGURE 30. Relative abundance of (a) CXCL10, (b) CXCL9, (c) IFNγ and (d) BATF2 in key patient groups within the GO/NO-GO cohort for assessment of the candidate molecular rule-out test.
FIGURE 30. Relative abundance of (a) CXCL10, (b) CXCL9, (c) IFNγ and (d) BATF2 in key patient groups within the GO/NO-GO cohort for assessment of the candidate molecular rule-out test.

FIGURE 30

Relative abundance of (a) CXCL10, (b) CXCL9, (c) IFNγ and (d) BATF2 in key patient groups within the GO/NO-GO cohort for assessment of the candidate molecular rule-out test. The cut-off points shown are the level of expression required for the test to provide > 95% sensitivity for all active TB cases. HIV+ individuals are shown in green triangles. The gene expression cut-off values for achieving 95% sensitivity for all TB cases are displayed. Statistical differences between groups were determined using Kruskal–Wallis with Dunn’s post hoc test for multiple comparisons. ATB, active tuberculosis; mRNA, messenger ribonucleic acid. *p < 0.05; **p < 0.005; ***p < 0.0005; ****p < 0.0001.

FIGURE 31. Selection of cut-off point for target genes (a) CXCL10; (b) CXCL9; and (c) BATF2 in response to IFNγ-positive control condition.
FIGURE 31. Selection of cut-off point for target genes (a) CXCL10; (b) CXCL9; and (c) BATF2 in response to IFNγ-positive control condition.
FIGURE 31. Selection of cut-off point for target genes (a) CXCL10; (b) CXCL9; and (c) BATF2 in response to IFNγ-positive control condition.

FIGURE 31

Selection of cut-off point for target genes (a) CXCL10; (b) CXCL9; and (c) BATF2 in response to IFNγ-positive control condition. ATB, active tuberculosis.

TABLE 56

TABLE 56

Measurement of IFNγ transcripts in stimulated PBMC samples using qRT-PCR

TABLE 57. Diagnostic accuracy data for candidate molecular rule-out test: all TB vs.

TABLE 57

Diagnostic accuracy data for candidate molecular rule-out test: all TB vs. all OD

FIGURE 32. Diagnostic performance of CXCL10, CXCL9, IFNγ and BATF2Mtb-specific gene expression in all TB vs.

FIGURE 32

Diagnostic performance of CXCL10, CXCL9, IFNγ and BATF2Mtb-specific gene expression in all TB vs. T-SPOT.TB test-negative OD.

TABLE 58. Diagnostic accuracy data for candidate molecular rule-out test: all TB vs.

TABLE 58

Diagnostic accuracy data for candidate molecular rule-out test: all TB vs. T-SPOT.TB test-negative OD

TABLE 59. Diagnostic accuracy data for candidate molecular rule-out test: T-SPOT.

TABLE 59

Diagnostic accuracy data for candidate molecular rule-out test: T-SPOT.TB test-positive TB vs. T-SPOT.TB test-negative OD

FIGURE 33. Diagnostic performance of CXCL10, CXCL9, IFNγ and BATF2Mtb-specific gene expression in T-SPOT.

FIGURE 33

Diagnostic performance of CXCL10, CXCL9, IFNγ and BATF2Mtb-specific gene expression in T-SPOT.TB test-positive TB vs. T-SPOT.TB test-negative OD.

FIGURE 34. The performance of qRT-PCR detection of CXCL10, CXCL9, IFNγ, BATF2 and T-SPOT for discriminating between T-SPOT.

FIGURE 34

The performance of qRT-PCR detection of CXCL10, CXCL9, IFNγ, BATF2 and T-SPOT for discriminating between T-SPOT.TB-positive TB cases (n = 19–24) and T-SPOT.TB-positive OD/LTBI cases (n = 10–22).

TABLE 60. Diagnostic accuracy data for candidate molecular rule-out test: T-SPOT.

TABLE 60

Diagnostic accuracy data for candidate molecular rule-out test: T-SPOT.TB test-positive ATB vs. T-SPOT.TB test-positive

TABLE 61

TABLE 61

Performance of IFNγ and CXCL10 analytes from QuantiFERON supernatants detected by MSD for the detection of all TB in the GO/NO-GO cohort

FIGURE 35. Comparison of detection of IFNγ or CXCL10 in Mtb antigen-stimulated samples.
FIGURE 35. Comparison of detection of IFNγ or CXCL10 in Mtb antigen-stimulated samples.
FIGURE 35. Comparison of detection of IFNγ or CXCL10 in Mtb antigen-stimulated samples.

FIGURE 35

Comparison of detection of IFNγ or CXCL10 in Mtb antigen-stimulated samples. (a) Using either MSD from QFT-GIT supernatants of qRT-PCR from stimulated PBMCs; (b) comparing between patient groups in the overlapping cohort (n = 75), where both tests were performed; and (c) the diagnostic accuracy of using either IFNγ or CXCL10 using either platform, for detection all TB cases, was assessed by ROC curve analysis. Protein levels and fold changes in gene expression were compared between groups using Kruskal–Wallis with Dunn’s post hoc test for multiple comparisons. ATB, active tuberculosis. *p < 0.05; **p < 0.005; ***p < 0.0005; ****p < 0.0001.

Copyright © Queen’s Printer and Controller of HMSO 2021. This work was produced by Halliday et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK.
Bookshelf ID: NBK569471
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