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Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@6121c9d6 Item: Title: TB1 and TB2 interferon-γ response among contacts. Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@87f383f Item: Title: TB2−TB1 value >0.6⁜琀䤀唀뜀洀氢ሀ㄀ 愀猀 愀 瀀爀攀搀椀挀琀漀爀 漀昀 最爀攀愀琀攀爀 爀椀猀欀 漀昀 爀攀挀攀渀琀 攀砀瀀漀猀甀爀攀⸩⽄敳琨slink3 Item: Title: DISCUSSION Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4eb7f003 Item: Title: MATERIALS AND METHODS Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@eafc191 Children: Item: Title: Study design and participants. Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@612fc6eb Item: Title: Data collection and analysis. Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1060b431 Item: Title: Ethics. Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@612679d6 Item: Title: Data availability. 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NCMIMI+AdvPSMP12 Flags: Nonsymbolic FontBBox: -10, -229, 1062, 697 FontFile3: true Encoding: WinAnsiEncoding XMP: Identification of Recent Tuberculosis Exposure Using QuantiFERON-TB Gold Plus, a Multicenter Study 10.1128/Spectrum.00972-21 Sandra Pérez-Recio Natàlia Pallarès Maria D. Grijota-Camino Adrián Sánchez-Montalvá Laura Barcia Silvia Campos-Gutiérrez Virginia Pomar Ramón Rabuñal-Rey María Elvira Balcells Deniz Gazel Natalia Montiel Diego Vicente Ivana Goić-Barišić Thomas Schön Jakob Paues Ivana Mareković Juana Cacho-Calvo Aleksandra Barac Delia Goletti Mercedes García-Gasalla José María Barcala María Teresa Tórtola Luis Anibarro Isabel Suárez-Toste Esther Moga María J. Gude-Gonzalez Rodrigo Naves Tekin Karslıgil Tania Martin-Peñaranda Goran Stevanovic Matilde Trigo Verónica Rubio İlkay Karaoğlan Nazan Bayram Fernando Alcaide Cristian Tebé Miguel Santin Research Article Research Article QuantiFERON-TB gold plus diagnosis latent tuberculosis infection tuberculosis-specific CD8 T cells American Society for Microbiology Pérez-Recio et al. Copyright © 2021 Pérez-Recio et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license. 20211110 2021 ABSTRACT We investigated whether the difference of antigen tube 2 (TB2) minus antigen tube 1 (TB1) (TB2−TB1) of the QuantiFERON-TB gold plus test, which has been postulated as a surrogate for the CD8+ T-cell response, could be useful in identifying recent tuberculosis (TB) exposure. We looked at the interferon gamma (IFN-γ) responses and differences in TB2 and TB1 tubes for 686 adults with QFT-plus positive test results. These results were compared among groups with high (368 TB contacts), low (229 patients with immune-mediated inflammatory diseases [IMID]), and indeterminate (89 asylum seekers or people from abroad [ASPFA]) risks of recent TB exposure. A TB2−TB1 value >0.6 IU·ml−1 was deemed to indicate a true difference between tubes. In the whole cohort, 13.6%, 10.9%, and 11.2% of cases had a TB2>TB1 result in the contact, IMID, and ASPFA groups, respectively (P = 0.591). The adjusted odds ratios (aORs) for an association between a TB2−TB1 result of >0.6 IU·ml−1 and risk of recent exposure versus contacts were 0.71 (95% confidence interval [CI], 0.31 to 1.61) for the IMID group and 0.86 (95% CI, 0.49 to 1.52) for the ASPFA group. In TB contact subgroups, 11.4%, 15.4%, and 17.7% with close, frequent, and sporadic contact had a TB2>TB1 result (P = 0.362). The aORs versus the close subgroup were 1.29 (95% CI, 0.63 to 2.62) for the frequent subgroup and 1.55 (95% CI, 0.67 to 3.60) for the sporadic subgroup. A TB2−TB1 difference of >0.6 IU·ml−1 was not associated with increased risk of recent TB exposure, which puts into question the clinical potential as a proxy marker for recently acquired TB infection. IMPORTANCE Contact tuberculosis tracing is essential to identify recently infected people, who therefore merit preventive treatment. However, there are no diagnostic tests that can determine whether the infection is a result of a recent exposure or not. It has been suggested that by using the QuantiFERON-TB gold plus, an interferon gamma (IFN-γ) release assay, a difference in IFN-γ production between the two antigen tubes (TB2 minus TB1) of >0.6 IU·ml−1 could serve as a proxy marker for recent infection. In this large multinational study, infected individuals could not be classified according to the risk of recent exposure based on differences in IFN-γ in TB1 and TB2 tubes that were higher than 0.6 IU·ml−1. QuantiFERON-TB gold plus is not able to distinguish between recent and remotely acquired tuberculosis infection, and it should not be used for that purpose in contact tuberculosis tracing. 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