We have previously published systematic and narrative reviews on IGRA accuracy and performance in various subgroups [5] (link), [6] (link), [12] (link), [13] (link), [14] (link)). We updated the database searches that were done in previous systematic reviews and searched the literature for relevant IGRA studies (up to November 2009) that reported data on within-subject variability of IGRAs and/or data on effect of TST on subsequent IGRA results. We searched PubMed, Embase and Biosis and Web of Science, and reviewed citations of all original articles published in all languages.
The search terms used in database searching included: ((interferon-gamma release assay*) OR (T-cell-based assay*) OR (antigen-specific T cell*) OR (T cell response*) OR (T-cell response*) OR (interferon*) OR (interferon-gamma) OR (gamma-interferon) OR (IFN) OR (elispot) OR (ESAT-6) OR (CFP-10) OR (culture filtrate protein) OR (Enzyme Linked Immunosorbent Spot) OR (Quantiferon* OR Quantiferon-TB Gold)) AND ((tuberculosis OR mycobacterium tuberculosis)).
In addition to database searches, we reviewed bibliographies of previous reviews and guidelines on IGRAs, and also screened the citations of relevant original articles. Experts in the field and commercial test manufacturers were also contacted to obtain relevant citations. No language restrictions were imposed and full-length papers as well as conference abstracts were included (to limit potential publication bias).
We included studies of QuantiFERON-TB Gold (QFT-G, also known as QFT-2G), QuantiFERON-TB Gold In-Tube (QFT-GIT, also known as QFT-3G) [Cellestis Limited, Victoria, Australia], and the T-SPOT.TB [Oxford Immunotec, Oxford, UK] or its pre-commercial ELISPOT version. Where relevant, we included in-house, short-incubation (overnight) IFN-γ assays with RD1 antigens as well, to increase the number of relevant studies.
For studies assessing reproducibility (defined as within-subject repeatability over time, under similar conditions), the study had to have repeated (at least two) IGRA assays (same IGRA) done on the same group of subjects, preferably in a setting with limited TB exposure and without an antecedent TST within 6 months. If reproducibility was done in a high TB incidence setting where exposure-related changes are likely, then repeat tests should have been done over a short period of <6 weeks (to avoid the confusion between conversions (or new infections) and natural variations in T-cell responses). For studies assessing boosting of IGRA results due to a prior TST, the study sample must have had at least one IGRA assay done before and after tuberculin skin testing and not performed in the context of a contact or outbreak study in a high incidence setting (again, to avoid the confusion between true conversion and boosting).
We did not consider reproducibility data where two or more tests were done on the same sample at the same time (e.g. two tests done using samples from the same blood draw); this would not have been informative for our objective of determining the within-person variability when the test is repeated over time (serial testing). Also, we did not consider other forms of reproducibility data, such as inter-laboratory variation, variations between lab technologists, batch-to-batch variations, variations due to different incubation times, etc.
The search terms used in database searching included: ((interferon-gamma release assay*) OR (T-cell-based assay*) OR (antigen-specific T cell*) OR (T cell response*) OR (T-cell response*) OR (interferon*) OR (interferon-gamma) OR (gamma-interferon) OR (IFN) OR (elispot) OR (ESAT-6) OR (CFP-10) OR (culture filtrate protein) OR (Enzyme Linked Immunosorbent Spot) OR (Quantiferon* OR Quantiferon-TB Gold)) AND ((tuberculosis OR mycobacterium tuberculosis)).
In addition to database searches, we reviewed bibliographies of previous reviews and guidelines on IGRAs, and also screened the citations of relevant original articles. Experts in the field and commercial test manufacturers were also contacted to obtain relevant citations. No language restrictions were imposed and full-length papers as well as conference abstracts were included (to limit potential publication bias).
We included studies of QuantiFERON-TB Gold (QFT-G, also known as QFT-2G), QuantiFERON-TB Gold In-Tube (QFT-GIT, also known as QFT-3G) [Cellestis Limited, Victoria, Australia], and the T-SPOT.TB [Oxford Immunotec, Oxford, UK] or its pre-commercial ELISPOT version. Where relevant, we included in-house, short-incubation (overnight) IFN-γ assays with RD1 antigens as well, to increase the number of relevant studies.
For studies assessing reproducibility (defined as within-subject repeatability over time, under similar conditions), the study had to have repeated (at least two) IGRA assays (same IGRA) done on the same group of subjects, preferably in a setting with limited TB exposure and without an antecedent TST within 6 months. If reproducibility was done in a high TB incidence setting where exposure-related changes are likely, then repeat tests should have been done over a short period of <6 weeks (to avoid the confusion between conversions (or new infections) and natural variations in T-cell responses). For studies assessing boosting of IGRA results due to a prior TST, the study sample must have had at least one IGRA assay done before and after tuberculin skin testing and not performed in the context of a contact or outbreak study in a high incidence setting (again, to avoid the confusion between true conversion and boosting).
We did not consider reproducibility data where two or more tests were done on the same sample at the same time (e.g. two tests done using samples from the same blood draw); this would not have been informative for our objective of determining the within-person variability when the test is repeated over time (serial testing). Also, we did not consider other forms of reproducibility data, such as inter-laboratory variation, variations between lab technologists, batch-to-batch variations, variations due to different incubation times, etc.
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