Within-Subject Variability and Boosting of T-Cell Interferon-γ Responses after Tuberculin Skin Testing

Zyl-Smit, Richard van; Pai, Madhukar; Peprah, Kwaku; Meldau, Richard; Kieck, J; Juritz, J; Badri, Motasim; Zumla, Alimuddin; Sechi, Leonardo Antonio; Bateman, Eric D.; Dheda, Keertan

doi:10.1164/rccm.200811-1704oc

Cited by 165 publications

(160 citation statements)

References 30 publications

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“…Reversion was defined as the opposite progression. As previously proposed (21,29,32), uncertainty zones of 0.2 to 0.7 IU/ml (QFT) and 4 to 8 SFCs (T-SPOT) and increases from Ͻ0.35 to Ͼ0.7 IU/ml (QFT) and from Ͻ4 to Ͼ8 SFCs (T-SPOT) were used for borderline zone analysis and as definitions for conversions (and reversions), respectively.…”

Section: Methodsmentioning

confidence: 99%

“…Two recently published systematic reviews on the within-subject variability and performance in the serial testing of HCWs identified only 4 and 10 studies, respectively, which met the predefined eligibility criteria (33,37). Studies on reproducibility and within-subject variability were predominantly from high-incidence settings (India and South Africa) and included only small numbers of subjects (67 in total) (6,32,34). In contrast, serial testing studies were mostly from countries with a low to intermediate TB incidence (5,13,20,(24)(25)(26)36).…”

mentioning

confidence: 99%

“…Various borderline zones around the manufacturers' thresh-olds and definitions of conversions and reversions have been proposed to improve their interpretation in serial testing (15,20,21,24,32,34). Apparently, the performance of IGRAs depends on the population and epidemiologic setting in which these tests are applied (9).…”

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confidence: 99%

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Within-Subject Variability of Mycobacterium tuberculosis-Specific Gamma Interferon Responses in German Health Care Workers

Ringshausen

Nienhaus

Costa

et al. 2011

Clin. Vaccine Immunol.

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Gamma interferon (IFN-␥) release assays (IGRAs) are used increasingly for the periodic tuberculosis (TB) screening of health care workers (HCWs), although data regarding the reproducibility and interpretation of serial testing results in countries with a low incidence of TB are scarce. The present study evaluated and compared the within-subject variability of dichotomous and continuous results of two commercial IGRAs, the QuantiFERON-TB Gold In-Tube (QFT) and the T-SPOT.TB (T-SPOT), in German HCWs during a 4-week period. Thirty-five immunocompetent HCWs with low or medium TB screening risk and without known recent TB exposure or tuberculin skin test application were tested repeatedly with both IGRAs at weekly intervals. A total of 158 valid results were obtained for each IGRA. Changes of about ؎70% (QFT) and ؎60% (T-SPOT) from the mean IFN-␥ response accounted for 95% of the within-subject variability. However, according to the manufacturers' cutoffs, inconsistent results were observed more frequently for the QFT (28.6%; four conversions, six reversions) than for the T-SPOT (8.6%; three reversions; P < 0.001). The overall agreement between the IGRAs was good. Regression toward the means accounted for a significant decline in mean IFN-␥ responses of about 25% between successive visits for both IGRAs. Although both assays were highly reliable and reproducible, we observed substantial within-subject variability and regression toward the means during a 4-week period, which should be considered when interpreting serial testing results in comparable populations and settings. Our data support the use of borderline zones for the interpretation of serial IGRA results and the retesting of borderline positive results before offering preventive chemotherapy.

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Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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Within-Subject Variability of Mycobacterium tuberculosis-Specific Gamma Interferon Responses in German Health Care Workers

Ringshausen

Nienhaus

Costa

et al. 2011

Clin. Vaccine Immunol.

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“…Simply repeating optical density measurements of the ELISA test result after a time interval (up to 2 h) did not result in any variability (22,30). Three other studies, for which quantitative data were not available, assessed additional sources of QuantiFERON variability: diurnal variability, interlaboratory variation, and variability comparing the use of an automated versus manual ELISA (29,38,39).…”

Section: Systematic Reviewmentioning

confidence: 99%

“…A total of three studies used T-SPOT (6,22,30) and assessed variability under the same conditions (125 subjects) on repeat testing over time (270 subjects) and boosting by negative skin test (63 subjects). Percent of conversions and reversions are summarized in Table 4; variation of results on repeat testing were not reported if the baseline test was in the borderline range (4.1-7.9 spot-forming units).…”

Section: Variability Of T-spotmentioning

confidence: 99%

Reproducibility of Interferon Gamma (IFN-γ) Release Assays. A Systematic Review

Tagmouti¹,

Slater

Benedetti

et al. 2014

Annals ATS

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Rationale: Interferon gamma (IFN-g) release assays for latent tuberculosis infection result in a larger-than-expected number of conversions and reversions in occupational screening programs, and reproducibility of test results is a concern.Objectives: Knowledge of the relative contribution and extent of the individual sources of variability (immunological, preanalytical, or analytical) could help optimize testing protocols. Methods:We performed a systematic review of studies published by October 2013 on all potential sources of variability of commercial IFN-g release assays (QuantiFERON-TB Gold In-Tube and T-SPOT.TB). The included studies assessed test variability under identical conditions and under different conditions (the latter both overall and stratified by individual sources of variability). Linear mixed effects models were used to estimate withinsubject SD. Measurements and Main Results:We identified a total of 26 articles, including 7 studies analyzing variability under the same conditions, 10 studies analyzing variability with repeat testing over time under different conditions, and 19 studies reporting individual sources of variability. Most data were on QuantiFERON (only three studies on T-SPOT.TB). A considerable number of conversions and reversions were seen around the manufacturer-recommended cut-point. The estimated range of variability of IFN-g response in QuantiFERON under identical conditions was 60.47 IU/ml (coefficient of variation, 13%) and 60.26 IU/ml (30%) for individuals with an initial IFN-g response in the borderline range (0.25-0.80 IU/ml). The estimated range of variability in noncontrolled settings was substantially larger (61.4 IU/ml; 60%). Blood volume inoculated into QuantiFERON tubes and preanalytic delay were identified as key sources of variability.Conclusions: This systematic review shows substantial variability with repeat IFN-g release assays testing even under identical conditions, suggesting that reversions and conversions around the existing cut-point should be interpreted with caution.

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Recent Advances in the Treatment of Latent Tuberculosis Infection Among Adults Living with HIV Infection

Pettit

2019

HIV and Tuberculosis

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Within-Subject Variability and Boosting of T-Cell Interferon-γ Responses after Tuberculin Skin Testing

Cited by 165 publications

References 30 publications

Within-Subject Variability of Mycobacterium tuberculosis-Specific Gamma Interferon Responses in German Health Care Workers

Within-Subject Variability of Mycobacterium tuberculosis-Specific Gamma Interferon Responses in German Health Care Workers

Reproducibility of Interferon Gamma (IFN-γ) Release Assays. A Systematic Review

Recent Advances in the Treatment of Latent Tuberculosis Infection Among Adults Living with HIV Infection

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