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Within-subject variability and boosting of t-cell interferon-γ responses after tuberculin skin testing

Zyl-Smit, Richard N. van and Pai, Madhukar and Peprah, Kwaku and Meldau, Richard and Kieck, Jackie and Juritz, June and Badri, Motasim and Zumla, Alimuddin and Sechi, Leonardo Antonio and Bateman, Eric D. and Dheda, Keertan (2009) Within-subject variability and boosting of t-cell interferon-γ responses after tuberculin skin testing. American Journal of Respiratory and Critical Care Medicine, Vol. 180 (1), p. 49-58. eISSN 0003-0805. Article.

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DOI: 10.1164/rccm.200811-1704OC


Rationale: The optimal strategy for the diagnosis of latent tuberculosis infection is controversial. Adoption of a two-step strategy (tuberculin skin test [TST] followed by an IFN-γ release assay [IGRA], compared with an IGRA alone), may be limited by TST-mediated boosting of subsequent IGRA responses. Assessment of within-subject IGRA variability will aid in establishing thresholds for conversions and reversions, and interpretation of serial testing results.
Objectives: To determine short-term IGRA variability and the impact of TST on subsequent IGRA results.
Methods: Within-subject variability and TST-mediated boosting of IGRA responses were evaluated in 26 South African participants with varying exposure risk. IGRAs (T-SPOT.TB, QuantiFERON-TB Gold In-Tube [QuantiFERON-TB-GIT], PPD, and heparin-binding hemagglutinin) were repeated four times over 21 days pre-TST, and on Days 3, 7, 28, and 84 post-TST administration.
Measurements and Main Results: All participants showed within-subject IGRA variability. Changes of ±3 spots (T-SPOT.TB) or ±80% from the mean IFN-γ response (QuantiFERON-TB-GIT) over 3 weeks explained 95% of the variability. Spontaneous conversions/reversions occurred in 7 of 26 subjects (27%) (6 for T-SPOT.TB and 1 for QuantiFERON-TB-GIT [P= 0.049]) during the within-patient variability studies (pre-TST). After the TST eight subjects (33%) boosted above the defined baseline variability. By Day 7 post-TST, but not Day 3, 2 (12.5%) initially IGRA-negative test subjects converted. By contrast, boosting of PPD and heparin-binding hemagglutinin occurred by Day 3 post-TST.
Conclusions: When using a two-step screening strategy it appears safe to perform a QuantiFERON-TB-GIT or T-SPOT.TB IGRA within 3 days of performing the TST. A 3-spot or 80% IFN-γ response variation, on either side of baseline values, explains 95% of the short-term variability and may be useful for interpreting conversions and reversions, and values close to the cut-point.

Item Type:Article
ID Code:3521
Uncontrolled Keywords:Latent tuberculosis, IFN-γ release assay, tuberculin skin test, variability, boosting
Subjects:Area 06 - Scienze mediche > MED/07 Microbiologia e microbiologia clinica
Divisions:001 Università di Sassari > 01 Dipartimenti > Scienze biomediche
Publisher:American Thoracic Society
Deposited On:25 Jan 2010 10:50

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