T-cell assays for tuberculosis infection: deriving cut-offs for conversions using reproducibility data.
<h4>Background</h4>Although interferon-gamma release assays (IGRA) are promising alternatives to the tuberculin skin test, interpretation of repeated testing results is hampered by lack of evidence on optimal cut-offs for conversions and reversions. A logical start is to determine the wi...
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Public Library of Science (PLoS)
2008-03-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0001850&type=printable |
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| author | Anandharaman Veerapathran Rajnish Joshi Kalyan Goswami Sandeep Dogra Erica E M Moodie M V R Reddy Shriprakash Kalantri Kevin Schwartzman Marcel A Behr Dick Menzies Madhukar Pai |
| author_facet | Anandharaman Veerapathran Rajnish Joshi Kalyan Goswami Sandeep Dogra Erica E M Moodie M V R Reddy Shriprakash Kalantri Kevin Schwartzman Marcel A Behr Dick Menzies Madhukar Pai |
| author_sort | Anandharaman Veerapathran |
| collection | DOAJ |
| description | <h4>Background</h4>Although interferon-gamma release assays (IGRA) are promising alternatives to the tuberculin skin test, interpretation of repeated testing results is hampered by lack of evidence on optimal cut-offs for conversions and reversions. A logical start is to determine the within-person variability of T-cell responses during serial testing.<h4>Methodology/principal findings</h4>We performed a pilot study in India, to evaluate the short-term reproducibility of QuantiFERON-TB Gold In Tube assay (QFT) among 14 healthcare workers (HCWs) who underwent 4 serial QFT tests on day 0, 3, 9 and 12. QFT ELISA was repeated twice on the same sets of specimens. We assessed two types of reproducibility: 1) test-retest reproducibility (between-test variability), and 2) within-person reproducibility over time. Test-retest reproducibility: with dichotomous test results, extremely high concordance was noticed between two tests performed on the same sets of specimens: of the 56 samples, the test and re-test results agreed for all but 2 individuals (kappa = 0.94). Discordance was noted in subjects who had IFN-gamma values around the cut-off point, with both increases and decreases noted. With continuous IFN-gamma results, re-test results tended to produce higher estimates of IFN-gamma than the original test. Within-person reproducibility: when continuous IFN-gamma data were analyzed, the within-person reproducibility was moderate to high. While persons with negative QFT results generally stayed negative, positive results tended to vary over time. Our data showed that increases of more than 16% in the IFN-gamma levels are statistically improbable in the short-term.<h4>Conclusions</h4>Conservatively assuming that long-term variability might be at least twice higher than short-term, we hypothesize that a QFT conversion requires two conditions to be met: 1) change from negative to positive result, and 2) at least 30% increase in the baseline IFN-gamma response. Larger studies are needed to confirm our preliminary findings, and determine the conversion thresholds for IGRAs. |
| format | Article |
| id | doaj-art-3d289b1dfd1547bc9a1f5e5443abdc39 |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2008-03-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS ONE |
| spelling | doaj-art-3d289b1dfd1547bc9a1f5e5443abdc392025-08-20T02:17:21ZengPublic Library of Science (PLoS)PLoS ONE1932-62032008-03-0133e185010.1371/journal.pone.0001850T-cell assays for tuberculosis infection: deriving cut-offs for conversions using reproducibility data.Anandharaman VeerapathranRajnish JoshiKalyan GoswamiSandeep DograErica E M MoodieM V R ReddyShriprakash KalantriKevin SchwartzmanMarcel A BehrDick MenziesMadhukar Pai<h4>Background</h4>Although interferon-gamma release assays (IGRA) are promising alternatives to the tuberculin skin test, interpretation of repeated testing results is hampered by lack of evidence on optimal cut-offs for conversions and reversions. A logical start is to determine the within-person variability of T-cell responses during serial testing.<h4>Methodology/principal findings</h4>We performed a pilot study in India, to evaluate the short-term reproducibility of QuantiFERON-TB Gold In Tube assay (QFT) among 14 healthcare workers (HCWs) who underwent 4 serial QFT tests on day 0, 3, 9 and 12. QFT ELISA was repeated twice on the same sets of specimens. We assessed two types of reproducibility: 1) test-retest reproducibility (between-test variability), and 2) within-person reproducibility over time. Test-retest reproducibility: with dichotomous test results, extremely high concordance was noticed between two tests performed on the same sets of specimens: of the 56 samples, the test and re-test results agreed for all but 2 individuals (kappa = 0.94). Discordance was noted in subjects who had IFN-gamma values around the cut-off point, with both increases and decreases noted. With continuous IFN-gamma results, re-test results tended to produce higher estimates of IFN-gamma than the original test. Within-person reproducibility: when continuous IFN-gamma data were analyzed, the within-person reproducibility was moderate to high. While persons with negative QFT results generally stayed negative, positive results tended to vary over time. Our data showed that increases of more than 16% in the IFN-gamma levels are statistically improbable in the short-term.<h4>Conclusions</h4>Conservatively assuming that long-term variability might be at least twice higher than short-term, we hypothesize that a QFT conversion requires two conditions to be met: 1) change from negative to positive result, and 2) at least 30% increase in the baseline IFN-gamma response. Larger studies are needed to confirm our preliminary findings, and determine the conversion thresholds for IGRAs.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0001850&type=printable |
| spellingShingle | Anandharaman Veerapathran Rajnish Joshi Kalyan Goswami Sandeep Dogra Erica E M Moodie M V R Reddy Shriprakash Kalantri Kevin Schwartzman Marcel A Behr Dick Menzies Madhukar Pai T-cell assays for tuberculosis infection: deriving cut-offs for conversions using reproducibility data. PLoS ONE |
| title | T-cell assays for tuberculosis infection: deriving cut-offs for conversions using reproducibility data. |
| title_full | T-cell assays for tuberculosis infection: deriving cut-offs for conversions using reproducibility data. |
| title_fullStr | T-cell assays for tuberculosis infection: deriving cut-offs for conversions using reproducibility data. |
| title_full_unstemmed | T-cell assays for tuberculosis infection: deriving cut-offs for conversions using reproducibility data. |
| title_short | T-cell assays for tuberculosis infection: deriving cut-offs for conversions using reproducibility data. |
| title_sort | t cell assays for tuberculosis infection deriving cut offs for conversions using reproducibility data |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0001850&type=printable |
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