Diagnostic accuracy and predictive value of the QuantiFERON-TB gold plus assay for tuberculosis in immunocompromised individuals: a prospective TBnet study

Martina Sester; Neus Altet-Gomez; Åse Bengaard Andersen; Miguel Arias-Guillén; Korkut Avsar; Anne Marte Bakken Kran; Graham Bothamley; Anne Christine Nordholm Breschel; James Brown; Dumitru Chesov; Nelly Ciobanu; Daniela Maria Cirillo; Valeriu Crudu; Malu de Souza Galvao; Asli Görek Dilektasli; José Dominguez; Raquel Duarte; Anne Ma Dyrhol-Riise; Delia Goletti; Harald Hoffmann; Elmira Ibraim; Barbara Kalsdorf; Marcin Krawczyk; Heinke Kunst; Berit Lange; Marc Lipman; Alberto Matteelli; Piotr Milkiewicz; David Neyer; Martin Nitschke; Haluk Barbaros Oral; Juan José Palacios-Gutiérrez; Elisa Petruccioli; Joanna Raszeja-Wyszomirska; Pernille Ravn; Jan Rupp; Hanna Elisa Spohn; Corina Toader; Raquel Villar-Hernandez; Dirk Wagner; Frank van Leth; Leonardo Martinez; Ole Skouvig Pedersen; Christoph Lange

doi:10.1016/j.lanepe.2025.101416

Diagnostic accuracy and predictive value of the QuantiFERON-TB gold plus assay for tuberculosis in immunocompromised individuals: a prospective TBnet study

Martina Sester^*, Neus Altet-Gomez, Åse Bengaard Andersen, Miguel Arias-Guillén, Korkut Avsar, Anne Marte Bakken Kran, Graham Bothamley, Anne Christine Nordholm Breschel, James Brown, Dumitru Chesov, Nelly Ciobanu, Daniela Maria Cirillo, Valeriu Crudu, Malu de Souza Galvao, Asli Görek Dilektasli, José Dominguez, Raquel Duarte, Anne Ma Dyrhol-Riise, Delia Goletti, Harald HoffmannElmira Ibraim, Barbara Kalsdorf, Marcin Krawczyk, Heinke Kunst, Berit Lange, Marc Lipman, Alberto Matteelli, Piotr Milkiewicz, David Neyer, Martin Nitschke, Haluk Barbaros Oral, Juan José Palacios-Gutiérrez, Elisa Petruccioli, Joanna Raszeja-Wyszomirska, Pernille Ravn, Jan Rupp, Hanna Elisa Spohn, Corina Toader, Raquel Villar-Hernandez, Dirk Wagner, Frank van Leth, Leonardo Martinez, Ole Skouvig Pedersen, Christoph Lange

^*Korrespondierende/r Autor/-in für diese Arbeit

10 Zitate (Scopus)

Abstract

Background: In low tuberculosis (TB)-endemic countries, tuberculosis preventive therapy (TPT) is recommended for immunocompromised individuals with a positive immunodiagnostic test. This study aimed to assess the performance of the QuantiFERON-TB Gold Plus (QFT+) assay and predictive power for future tuberculosis in immunocompromised individuals. Methods: In this prospective observational study, immunocompromised adults ≥18 years of age including people living with HIV (PLHIV), chronic renal failure, rheumatoid arthritis, solid-organ transplantation or stem-cell transplantation, and immunocompetent adults with and without TB-disease were recruited at 21 sites in 11 European countries and tested with the QFT+ assay. Individuals without TB-disease were followed up for the development of tuberculosis. TB incidence rates (IR) were calculated, stratified by QFT+ results and acceptance of TPT. This study is registered with Clinicaltrials.gov, NCT02639936. Findings: A total of 2663 individuals (1115 female, 1548 male) were enrolled from 03/11/2015 to 29/03/2019. Persons without tuberculosis were followed up for at least two years. Among 1758 immunocompromised individuals without active tuberculosis, 13.6% had positive QFT+ results. Sensitivity and specificity for TB-disease were 70.0% (52.1–83.3%) and 91.4% (89.6–92.9%), respectively, in immunocompromised, and 81.4% (76.6–85.3%) and 96.0% (92.5–97.9%), respectively, in immunocompetent individuals. During 2457 cumulative years of follow-up among 932 individuals with chronic renal failure, rheumatoid arthritis, solid-organ transplantation or stem-cell transplantation, including 83 persons with a positive QFT+ test without TPT, no-one developed active tuberculosis. In contrast, among 642 PLHIV without TPT, one with an indeterminate QFT+ and 3/30 individuals with a positive QFT+ developed active tuberculosis; all had detectable HIV-replication and low CD4 T-cell counts (incidence 4.1 (95% CI (1.3–12.4) per 100 person-years). No individuals receiving TPT developed active tuberculosis during 269 years of follow-up. Interpretation: In immunocompromised individuals in low TB-endemic countries, the 2-year-risk for active tuberculosis was highest among PLHIV with detectable HIV-replication and low CD4-counts. In this study, the QFT+ assay did not strongly predict progression to active tuberculosis, which emphasises the need to incorporate additional risk factors. Funding: None.

Originalsprache	Englisch
Aufsatznummer	101416
Zeitschrift	The Lancet Regional Health - Europe
Jahrgang	57
Seiten (von - bis)	101416
ISSN	2666-7762
DOIs	https://doi.org/10.1016/j.lanepe.2025.101416
Publikationsstatus	Veröffentlicht - 10.2025

Fördermittel

The authors thank the following persons for their support during the study: Paola Mantegani, IRCCS San Raffaele Scientific Institute, Milan, Italy; Dr. Adrian Abagiu, Matei Bals Institute for Infectious Diseases in Bucharest, Romania; Franziska Daduna, Research center Borstel, Germany; Candida Guckelmus, Department of Transplant and Infection Immunology, Saarland University, Germany. Other sources of support: This study was investigator-initiated without 3rd party funding. For this study QuantiFERON-TB Gold Plus tests kits were donated to TBnet by the manufacturer (Qiagen, Hilden, Germany). Qiagen had no role in the idea, design and conduction of the study and had no access to study results at any time. C.L. is supported by the German Center for Infection Research (DZIF) under Grant agreement TTU-TB 02.709; DG and EP were partially supported by the Italian Ministry of Health , Ricerca Corrente, Linea 4.

Träger	Trägernummer
IRCCS San Raffaele Scientific Institute
Matei Bals Institute for Infectious Diseases in Bucharest
Deutsches Zentrum für Infektionsforschung	TTU-TB 02.709

UN SDGs

Dieser Output leistet einen Beitrag zu folgendem(n) Ziel(en) für nachhaltige Entwicklung

SDG 3 – Gesundheit und Wohlergehen

Strategische Forschungsbereiche und Zentren

Forschungsschwerpunkt: Infektion und Entzündung - Zentrum für Infektions- und Entzündungsforschung Lübeck (ZIEL)

DFG-Fachsystematik

2.21-03 Medizinische Mikrobiologie und Mykologie, Hygiene, Molekulare Infektionsbiologie
2.21-05 Immunologie

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10.1016/j.lanepe.2025.101416

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Sester, M., Altet-Gomez, N., Andersen, Å. B., Arias-Guillén, M., Avsar, K., Bakken Kran, A. M., Bothamley, G., Nordholm Breschel, A. C., Brown, J., Chesov, D., Ciobanu, N., Cirillo, D. M., Crudu, V., de Souza Galvao, M., Dilektasli, A. G., Dominguez, J., Duarte, R., Dyrhol-Riise, A. M., Goletti, D., ... Lange, C. (2025). Diagnostic accuracy and predictive value of the QuantiFERON-TB gold plus assay for tuberculosis in immunocompromised individuals: a prospective TBnet study. The Lancet Regional Health - Europe, 57, 101416. Artikel 101416. https://doi.org/10.1016/j.lanepe.2025.101416

@article{06ece0ec259d4515bf2da9c3b76f2c1a,

title = "Diagnostic accuracy and predictive value of the QuantiFERON-TB gold plus assay for tuberculosis in immunocompromised individuals: a prospective TBnet study",

abstract = "Background: In low tuberculosis (TB)-endemic countries, tuberculosis preventive therapy (TPT) is recommended for immunocompromised individuals with a positive immunodiagnostic test. This study aimed to assess the performance of the QuantiFERON-TB Gold Plus (QFT+) assay and predictive power for future tuberculosis in immunocompromised individuals. Methods: In this prospective observational study, immunocompromised adults ≥18 years of age including people living with HIV (PLHIV), chronic renal failure, rheumatoid arthritis, solid-organ transplantation or stem-cell transplantation, and immunocompetent adults with and without TB-disease were recruited at 21 sites in 11 European countries and tested with the QFT+ assay. Individuals without TB-disease were followed up for the development of tuberculosis. TB incidence rates (IR) were calculated, stratified by QFT+ results and acceptance of TPT. This study is registered with Clinicaltrials.gov, NCT02639936. Findings: A total of 2663 individuals (1115 female, 1548 male) were enrolled from 03/11/2015 to 29/03/2019. Persons without tuberculosis were followed up for at least two years. Among 1758 immunocompromised individuals without active tuberculosis, 13.6\% had positive QFT+ results. Sensitivity and specificity for TB-disease were 70.0\% (52.1–83.3\%) and 91.4\% (89.6–92.9\%), respectively, in immunocompromised, and 81.4\% (76.6–85.3\%) and 96.0\% (92.5–97.9\%), respectively, in immunocompetent individuals. During 2457 cumulative years of follow-up among 932 individuals with chronic renal failure, rheumatoid arthritis, solid-organ transplantation or stem-cell transplantation, including 83 persons with a positive QFT+ test without TPT, no-one developed active tuberculosis. In contrast, among 642 PLHIV without TPT, one with an indeterminate QFT+ and 3/30 individuals with a positive QFT+ developed active tuberculosis; all had detectable HIV-replication and low CD4 T-cell counts (incidence 4.1 (95\% CI (1.3–12.4) per 100 person-years). No individuals receiving TPT developed active tuberculosis during 269 years of follow-up. Interpretation: In immunocompromised individuals in low TB-endemic countries, the 2-year-risk for active tuberculosis was highest among PLHIV with detectable HIV-replication and low CD4-counts. In this study, the QFT+ assay did not strongly predict progression to active tuberculosis, which emphasises the need to incorporate additional risk factors. Funding: None.",

author = "Martina Sester and Neus Altet-Gomez and Andersen, \{{\AA}se Bengaard\} and Miguel Arias-Guill{\'e}n and Korkut Avsar and \{Bakken Kran\}, \{Anne Marte\} and Graham Bothamley and \{Nordholm Breschel\}, \{Anne Christine\} and James Brown and Dumitru Chesov and Nelly Ciobanu and Cirillo, \{Daniela Maria\} and Valeriu Crudu and \{de Souza Galvao\}, Malu and Dilektasli, \{Asli G{\"o}rek\} and Jos{\'e} Dominguez and Raquel Duarte and Dyrhol-Riise, \{Anne Ma\} and Delia Goletti and Harald Hoffmann and Elmira Ibraim and Barbara Kalsdorf and Marcin Krawczyk and Heinke Kunst and Berit Lange and Marc Lipman and Alberto Matteelli and Piotr Milkiewicz and David Neyer and Martin Nitschke and Oral, \{Haluk Barbaros\} and Palacios-Guti{\'e}rrez, \{Juan Jos{\'e}\} and Elisa Petruccioli and Joanna Raszeja-Wyszomirska and Pernille Ravn and Jan Rupp and Spohn, \{Hanna Elisa\} and Corina Toader and Raquel Villar-Hernandez and Dirk Wagner and \{van Leth\}, Frank and Leonardo Martinez and Pedersen, \{Ole Skouvig\} and Christoph Lange",

note = "{\textcopyright} 2025 The Author(s).",

year = "2025",

month = oct,

doi = "10.1016/j.lanepe.2025.101416",

language = "English",

volume = "57",

pages = "101416",

journal = "The Lancet Regional Health - Europe",

issn = "2666-7762",

publisher = "Elsevier Ltd",

}

Sester, M, Altet-Gomez, N, Andersen, ÅB, Arias-Guillén, M, Avsar, K, Bakken Kran, AM, Bothamley, G, Nordholm Breschel, AC, Brown, J, Chesov, D, Ciobanu, N, Cirillo, DM, Crudu, V, de Souza Galvao, M, Dilektasli, AG, Dominguez, J, Duarte, R, Dyrhol-Riise, AM, Goletti, D, Hoffmann, H, Ibraim, E, Kalsdorf, B, Krawczyk, M, Kunst, H, Lange, B, Lipman, M, Matteelli, A, Milkiewicz, P, Neyer, D, Nitschke, M, Oral, HB, Palacios-Gutiérrez, JJ, Petruccioli, E, Raszeja-Wyszomirska, J, Ravn, P, Rupp, J, Spohn, HE, Toader, C, Villar-Hernandez, R, Wagner, D, van Leth, F, Martinez, L, Pedersen, OS & Lange, C 2025, 'Diagnostic accuracy and predictive value of the QuantiFERON-TB gold plus assay for tuberculosis in immunocompromised individuals: a prospective TBnet study', The Lancet Regional Health - Europe, Jg. 57, 101416, S. 101416. https://doi.org/10.1016/j.lanepe.2025.101416

Diagnostic accuracy and predictive value of the QuantiFERON-TB gold plus assay for tuberculosis in immunocompromised individuals: a prospective TBnet study. / Sester, Martina; Altet-Gomez, Neus; Andersen, Åse Bengaard et al.
in: The Lancet Regional Health - Europe, Jahrgang 57, 101416, 10.2025, S. 101416.

Publikation: Beiträge in Fachzeitschriften › Zeitschriftenaufsätze › Forschung › Begutachtung

TY - JOUR

T1 - Diagnostic accuracy and predictive value of the QuantiFERON-TB gold plus assay for tuberculosis in immunocompromised individuals

T2 - a prospective TBnet study

AU - Sester, Martina

AU - Altet-Gomez, Neus

AU - Andersen, Åse Bengaard

AU - Arias-Guillén, Miguel

AU - Avsar, Korkut

AU - Bakken Kran, Anne Marte

AU - Bothamley, Graham

AU - Nordholm Breschel, Anne Christine

AU - Brown, James

AU - Chesov, Dumitru

AU - Ciobanu, Nelly

AU - Cirillo, Daniela Maria

AU - Crudu, Valeriu

AU - de Souza Galvao, Malu

AU - Dilektasli, Asli Görek

AU - Dominguez, José

AU - Duarte, Raquel

AU - Dyrhol-Riise, Anne Ma

AU - Goletti, Delia

AU - Hoffmann, Harald

AU - Ibraim, Elmira

AU - Kalsdorf, Barbara

AU - Krawczyk, Marcin

AU - Kunst, Heinke

AU - Lange, Berit

AU - Lipman, Marc

AU - Matteelli, Alberto

AU - Milkiewicz, Piotr

AU - Neyer, David

AU - Nitschke, Martin

AU - Oral, Haluk Barbaros

AU - Palacios-Gutiérrez, Juan José

AU - Petruccioli, Elisa

AU - Raszeja-Wyszomirska, Joanna

AU - Ravn, Pernille

AU - Rupp, Jan

AU - Spohn, Hanna Elisa

AU - Toader, Corina

AU - Villar-Hernandez, Raquel

AU - Wagner, Dirk

AU - van Leth, Frank

AU - Martinez, Leonardo

AU - Pedersen, Ole Skouvig

AU - Lange, Christoph

PY - 2025/10

Y1 - 2025/10

N2 - Background: In low tuberculosis (TB)-endemic countries, tuberculosis preventive therapy (TPT) is recommended for immunocompromised individuals with a positive immunodiagnostic test. This study aimed to assess the performance of the QuantiFERON-TB Gold Plus (QFT+) assay and predictive power for future tuberculosis in immunocompromised individuals. Methods: In this prospective observational study, immunocompromised adults ≥18 years of age including people living with HIV (PLHIV), chronic renal failure, rheumatoid arthritis, solid-organ transplantation or stem-cell transplantation, and immunocompetent adults with and without TB-disease were recruited at 21 sites in 11 European countries and tested with the QFT+ assay. Individuals without TB-disease were followed up for the development of tuberculosis. TB incidence rates (IR) were calculated, stratified by QFT+ results and acceptance of TPT. This study is registered with Clinicaltrials.gov, NCT02639936. Findings: A total of 2663 individuals (1115 female, 1548 male) were enrolled from 03/11/2015 to 29/03/2019. Persons without tuberculosis were followed up for at least two years. Among 1758 immunocompromised individuals without active tuberculosis, 13.6% had positive QFT+ results. Sensitivity and specificity for TB-disease were 70.0% (52.1–83.3%) and 91.4% (89.6–92.9%), respectively, in immunocompromised, and 81.4% (76.6–85.3%) and 96.0% (92.5–97.9%), respectively, in immunocompetent individuals. During 2457 cumulative years of follow-up among 932 individuals with chronic renal failure, rheumatoid arthritis, solid-organ transplantation or stem-cell transplantation, including 83 persons with a positive QFT+ test without TPT, no-one developed active tuberculosis. In contrast, among 642 PLHIV without TPT, one with an indeterminate QFT+ and 3/30 individuals with a positive QFT+ developed active tuberculosis; all had detectable HIV-replication and low CD4 T-cell counts (incidence 4.1 (95% CI (1.3–12.4) per 100 person-years). No individuals receiving TPT developed active tuberculosis during 269 years of follow-up. Interpretation: In immunocompromised individuals in low TB-endemic countries, the 2-year-risk for active tuberculosis was highest among PLHIV with detectable HIV-replication and low CD4-counts. In this study, the QFT+ assay did not strongly predict progression to active tuberculosis, which emphasises the need to incorporate additional risk factors. Funding: None.

AB - Background: In low tuberculosis (TB)-endemic countries, tuberculosis preventive therapy (TPT) is recommended for immunocompromised individuals with a positive immunodiagnostic test. This study aimed to assess the performance of the QuantiFERON-TB Gold Plus (QFT+) assay and predictive power for future tuberculosis in immunocompromised individuals. Methods: In this prospective observational study, immunocompromised adults ≥18 years of age including people living with HIV (PLHIV), chronic renal failure, rheumatoid arthritis, solid-organ transplantation or stem-cell transplantation, and immunocompetent adults with and without TB-disease were recruited at 21 sites in 11 European countries and tested with the QFT+ assay. Individuals without TB-disease were followed up for the development of tuberculosis. TB incidence rates (IR) were calculated, stratified by QFT+ results and acceptance of TPT. This study is registered with Clinicaltrials.gov, NCT02639936. Findings: A total of 2663 individuals (1115 female, 1548 male) were enrolled from 03/11/2015 to 29/03/2019. Persons without tuberculosis were followed up for at least two years. Among 1758 immunocompromised individuals without active tuberculosis, 13.6% had positive QFT+ results. Sensitivity and specificity for TB-disease were 70.0% (52.1–83.3%) and 91.4% (89.6–92.9%), respectively, in immunocompromised, and 81.4% (76.6–85.3%) and 96.0% (92.5–97.9%), respectively, in immunocompetent individuals. During 2457 cumulative years of follow-up among 932 individuals with chronic renal failure, rheumatoid arthritis, solid-organ transplantation or stem-cell transplantation, including 83 persons with a positive QFT+ test without TPT, no-one developed active tuberculosis. In contrast, among 642 PLHIV without TPT, one with an indeterminate QFT+ and 3/30 individuals with a positive QFT+ developed active tuberculosis; all had detectable HIV-replication and low CD4 T-cell counts (incidence 4.1 (95% CI (1.3–12.4) per 100 person-years). No individuals receiving TPT developed active tuberculosis during 269 years of follow-up. Interpretation: In immunocompromised individuals in low TB-endemic countries, the 2-year-risk for active tuberculosis was highest among PLHIV with detectable HIV-replication and low CD4-counts. In this study, the QFT+ assay did not strongly predict progression to active tuberculosis, which emphasises the need to incorporate additional risk factors. Funding: None.

UR - https://www.scopus.com/pages/publications/105012400750

UR - https://www.mendeley.com/catalogue/0d9d7c8c-e9e0-3c35-95fc-a62f054d24f6/

U2 - 10.1016/j.lanepe.2025.101416

DO - 10.1016/j.lanepe.2025.101416

M3 - Journal articles

C2 - 40823191

AN - SCOPUS:105012400750

SN - 2666-7762

VL - 57

SP - 101416

JO - The Lancet Regional Health - Europe

JF - The Lancet Regional Health - Europe

M1 - 101416

ER -

Diagnostic accuracy and predictive value of the QuantiFERON-TB gold plus assay for tuberculosis in immunocompromised individuals: a prospective TBnet study

Abstract

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