QuantiFERON-TB Gold In-Tube as a Confirmatory Test for Tuberculin Skin Test in Tuberculosis Contact Tracing: A Noninferiority Clinical Trial.

Laura Muñoz, Miguel Santin, Fernando Alcaide, Maria Jesús Ruíz-Serrano, Paloma Gijón, Elena Bermúdez, Angel Domínguez-Castellano, María Dolores Navarro, Encarnación Ramírez, Elvira Pérez-Escolano, María Dolores López-Prieto, José Gutiérrez-Rodriguez, Luis Anibarro, Laura Calviño, Matilde Trigo, Carmen Cifuentes, Mercedes García-Gasalla, Antoni Payeras, Oriol Gasch, Mateu Espasa, Ramon Agüero, Diego Ferrer, Xavier Casas, Araceli González-Cuevas, Alberto García-Zamalloa, Edurne Bikuña, María Lecuona, Rosa Galindo, Marta Ramírez-Lapausa, Raquel Carrillo, María Jesús Ruíz-Serrano, Paloma Gijón, Elena Bermúdez, Pedro Montilla, Ana Fernández-Cruz, Inmaculada Cabrero, Luisa Ramírez, Marta Herranz, Darío García de Viedma, Angel Domínguez-Castellano, María Dolores Navarro, Esperanza Villar Fernández, Gertrudis Morilla, Encarnación Ramírez, José M Carretero, Santiago Sandova, María Prieto, Luis Anibarro, Laura Calviño, Diana Sande, Alberto Pena, Matilde Trigo, Marta García-Campello, Rosario Olivera, Elvira Pérez-Escolano, Ignacio López, Felipe Barrera, María Dolores López-Prieto, José Gutiérrez-Rodríguez, Asunción Almendral, Carmen Cifuentes, Mercedes García-Gasalla, Antoni Payeras, Isabel Mir, Veronica Navarro, Araceli Serrano, Catalina Morey, Andrea Salom, Mónica Sanz, Victoria Fernadez-Baca, Laura Muñoz, Miguel Santin, Lucía González, Maria R Guerra, Jordi Dorca, Fernando Alcaide, Raquel Moure, Cristian Tebé Codormi, Anna Ferrer, Oriol Gasch, Ana Granados, Sonia Calzado, Luisa Fernández-Angulo, Adoración Torres, Mateu Espasa, Miquel Cruel, Ramón Agüero, Diego Ferrer, Juan J Ruiz, Mercedes Álvarez, Laura Cólera, Jesús Agüero, Jorge de-la-Fuente, Teresa Gimenez, Marta Ramírez-Lapausa, Raquel Carrillo, Arturo Noguerado, Olvido López-Mesonero, Cristina Cárdenas, Pilar Gómez, María del-Río, Alberto García-Zamalloa, José I Royo, Edurne Bikuña, Lourdes Urbieta, Jorge Taboada, Diego Vicente, Jesús M Muruaga, María J Arrizabalaga, Xavier Casas, Salud Vicedo, Araceli González-Cuevas, Gabriel Gil, María Lecuona, Rosa Galindo, Isabel Suárez-Toste, Hemily K Izaguirre, Francisca Guzán, Tirso Virgós

Screening strategies based on interferon-γ release assays in tuberculosis contact tracing may reduce the need for preventive therapy without increasing subsequent active disease. We conducted an open-label, randomized trial, to test the non-inferiority of a two-step strategy with the tuberculin skin test followed by QuantiFERON®-TB Gold In-Tube as a confirmatory test (the TST/QFT arm) to the standard TST-alone strategy (TST arm) for targeting preventive therapy in household contacts of tuberculosis. Participants were followed for 24 months after randomization. The primary endpoint was the development of tuberculosis, with a non-inferiority margin of 1.5 percentage points. A total of 871 contacts were randomized. Four contacts in the TST arm and two in the TST/QFT arm developed tuberculosis. In the modified intention-to-treat analysis, this accounted for 0.99% in the TST arm and 0.51% in the TST/QFT arm (-0.48% difference; 97.5% confidence interval [CI], -0.90% to 1.86%); in the per-protocol analysis, the corresponding rates were 1.67% and 0.82% in the TST and TST/QFT arms, respectively (-0.85% difference; 97.5% CI, -1.43% to 3.14%). Of the 792 contacts analyzed, 65.3% in the TST arm and 42.2% in the TST/QFT arm were diagnosed with tuberculosis infection (23.1% difference; 97.5% CI, 16.4% to 30.0%). In low-incidence settings, screening household contacts with the tuberculin skin test and using QuantiFERON®-TB Gold In-Tube as a confirmatory test is not inferior to TST-alone for preventing active tuberculosis, allowing a safe reduction of preventive treatments.