Within-subject variability of interferon-g assay results for tuberculosis and boosting effect of tuberculin skin testing: a systematic review

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dc.contributor.authorVan Zyl-Smit, Richard Nen_ZA
dc.contributor.authorZwerling, Aliceen_ZA
dc.contributor.authorDheda, Keertanen_ZA
dc.contributor.authorPai, Madhukaren_ZA
dc.date.accessioned2016-01-11T06:51:40Z
dc.date.available2016-01-11T06:51:40Z
dc.date.issued2009en_ZA
dc.description.abstractBACKGROUND: Variability in interferon-gamma release assays (IGRAs) results for tuberculosis has implications for interpretation of results close to the cut-point, and for defining thresholds for test conversion and reversion. However, little is known about the within-subject variability (reproducibility) of IGRAs. Several national guidelines recommend a two-step testing procedure (tuberculin skin test [TST] followed by IGRA) for the diagnosis of LTBI. However, the effect of a preceding TST on subsequent IGRA results has been reported in studies with apparently conflicting results. Methodology/FINDINGS: We conducted a systematic review to synthesize evidence on within-subject variability of IGRA results and the potential boosting effect of TST. We searched several databases and reviewed citations of previous reviews on IGRAs. We included studies using commercial IGRAs, in addition to non-commercial versions of the ELISPOT assay. Four studies, fulfilling our predefined criteria, examined within-subject variability and 13 studies evaluated TST effects on subsequent IGRA responses. Meta-analysis was not considered appropriate because of heterogeneity in study methods, assays, and populations. Although based on limited data, within-subject variability was present in all studies but the magnitude varied (16-80%) across studies. A TST induced "boosting" of IGRA responses was demonstrated in several studies and although more pronounced in IGRA-positive (i.e. sensitized) individuals, also occurred in a smaller but not insignificant proportion of IGRA-negative subjects. The TST appeared to affect IGRA responses only after 3 days and may apparently persist for several months, but evidence for this is weak. Conclusions/Significance Although reproducibility data are scarce, significant within person IGRA variability has been reported. If confirmed in more studies, this has implications for the interpretation of results close to the cut-point and for definition of conversions and reversions. Although the effect of TST on IGRA results is likely to be inconsequential in IGRA-positive subjects, in IGRA-negative subjects, the interpretation of results may be confounded by a preceding TST if administered more than 3 days prior to an IGRA.en_ZA
dc.identifier.apacitationVan Zyl-Smit, R. N., Zwerling, A., Dheda, K., & Pai, M. (2009). Within-subject variability of interferon-g assay results for tuberculosis and boosting effect of tuberculin skin testing: a systematic review. <i>PLoS One</i>, http://hdl.handle.net/11427/16254en_ZA
dc.identifier.chicagocitationVan Zyl-Smit, Richard N, Alice Zwerling, Keertan Dheda, and Madhukar Pai "Within-subject variability of interferon-g assay results for tuberculosis and boosting effect of tuberculin skin testing: a systematic review." <i>PLoS One</i> (2009) http://hdl.handle.net/11427/16254en_ZA
dc.identifier.citationvan Zyl-Smit, R. N., Zwerling, A., Dheda, K., & Pai, M. (2009). Within-subject variability of interferon-g assay results for tuberculosis and boosting effect of tuberculin skin testing: a systematic review. PloS one, 4(12), e8517. doi:10.1371/journal.pone.0008517en_ZA
dc.identifier.ris TY - Journal Article AU - Van Zyl-Smit, Richard N AU - Zwerling, Alice AU - Dheda, Keertan AU - Pai, Madhukar AB - BACKGROUND: Variability in interferon-gamma release assays (IGRAs) results for tuberculosis has implications for interpretation of results close to the cut-point, and for defining thresholds for test conversion and reversion. However, little is known about the within-subject variability (reproducibility) of IGRAs. Several national guidelines recommend a two-step testing procedure (tuberculin skin test [TST] followed by IGRA) for the diagnosis of LTBI. However, the effect of a preceding TST on subsequent IGRA results has been reported in studies with apparently conflicting results. Methodology/FINDINGS: We conducted a systematic review to synthesize evidence on within-subject variability of IGRA results and the potential boosting effect of TST. We searched several databases and reviewed citations of previous reviews on IGRAs. We included studies using commercial IGRAs, in addition to non-commercial versions of the ELISPOT assay. Four studies, fulfilling our predefined criteria, examined within-subject variability and 13 studies evaluated TST effects on subsequent IGRA responses. Meta-analysis was not considered appropriate because of heterogeneity in study methods, assays, and populations. Although based on limited data, within-subject variability was present in all studies but the magnitude varied (16-80%) across studies. A TST induced "boosting" of IGRA responses was demonstrated in several studies and although more pronounced in IGRA-positive (i.e. sensitized) individuals, also occurred in a smaller but not insignificant proportion of IGRA-negative subjects. The TST appeared to affect IGRA responses only after 3 days and may apparently persist for several months, but evidence for this is weak. Conclusions/Significance Although reproducibility data are scarce, significant within person IGRA variability has been reported. If confirmed in more studies, this has implications for the interpretation of results close to the cut-point and for definition of conversions and reversions. Although the effect of TST on IGRA results is likely to be inconsequential in IGRA-positive subjects, in IGRA-negative subjects, the interpretation of results may be confounded by a preceding TST if administered more than 3 days prior to an IGRA. DA - 2009 DB - OpenUCT DO - 10.1371/journal.pone.0008517 DP - University of Cape Town J1 - PLoS One LK - https://open.uct.ac.za PB - University of Cape Town PY - 2009 T1 - Within-subject variability of interferon-g assay results for tuberculosis and boosting effect of tuberculin skin testing: a systematic review TI - Within-subject variability of interferon-g assay results for tuberculosis and boosting effect of tuberculin skin testing: a systematic review UR - http://hdl.handle.net/11427/16254 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/16254
dc.identifier.urihttp://dx.doi.org/10.1371/journal.pone.0008517
dc.identifier.vancouvercitationVan Zyl-Smit RN, Zwerling A, Dheda K, Pai M. Within-subject variability of interferon-g assay results for tuberculosis and boosting effect of tuberculin skin testing: a systematic review. PLoS One. 2009; http://hdl.handle.net/11427/16254.en_ZA
dc.language.isoengen_ZA
dc.publisherPublic Library of Scienceen_ZA
dc.publisher.departmentDivision of Pulmonologyen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_ZA
dc.rights.holder© 2009 van Zyl-Smit et alen_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/4.0en_ZA
dc.sourcePLoS Oneen_ZA
dc.source.urihttp://journals.plos.org/plosoneen_ZA
dc.subject.otherTuberculosisen_ZA
dc.subject.otherReproducibilityen_ZA
dc.subject.otherDatabase searchingen_ZA
dc.subject.otherSkin testsen_ZA
dc.subject.otherSystematic reviewsen_ZA
dc.subject.otherTuberculinen_ZA
dc.subject.otherEnzyme-linked immunoassaysen_ZA
dc.subject.otherT cellsen_ZA
dc.titleWithin-subject variability of interferon-g assay results for tuberculosis and boosting effect of tuberculin skin testing: a systematic reviewen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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