title: Clinical Application of Interferon-γ Release Assays for the Prevention of Tuberculosis in Countries with Low Incidence.
abstract: Despite global efforts to control tuberculosis (TB) the estimated number of people who developed TB worldwide increased to an all-time record of more than 10 million in 2015. The goal of the World Health Organization (WHO) to reduce the global incidence of TB to less than 100 cases per million by 2035, cannot be reached unless TB prevention is markedly improved. There is a need for an improved vaccine that better protects individuals who are exposed toMycobacterium tuberculosisfrom infection and active disease compared to the currentM. bovisBacille Calmette Guérin (BCG) vaccine. In the absence of such a vaccine, prevention relies on infection control measures and preventive chemotherapy for people with latent infection withM. tuberculosis(LTBI), who have the highest risk of progression to active TB. During the past decade, interferon-γ release assays (IGRAs) have increasingly replaced the tuberculin skin test as screening tools for the diagnosis of LTBI in countries with a low incidence of TB. Despite recent WHO guidelines on the management of LTBI, the definition of groups at risk for TB remains controversial, and the role of IGRAs for TB prevention in low-incidence countries remains uncertain. We reviewed the scientific literature and provide recommendations for the use of IGRAs for LTBI diagnosis in low-incidence countries. These recommendations are based on the number of patients needing treatment in order to prevent one case of TB. As the positive predictive value of IGRAs for the development of TB is sub-optimal, research must focus on the identification of alternative biomarkers that offer better predictive ability in order to substantially reduce the number needing treatment while improving the prevention of TB and improving the effectiveness of targeted preventive chemotherapy.
authors.affiliation: Division of Clinical Infectious Diseases, Medical Clinic Research Center Borstel, Borstel, Germany; German Center for Infection Research (DZIF), Clinical Tuberculosis Center, Borstel, Germany; International Health/Infectious Diseases, University of Lübeck, Lübeck, Germany; Department of Medicine, Karolinska Institute, Stockholm, Sweden; Department of Internal Medicine, University of Namibia School of Medicine, Windhoek, Namibia.
authors.forename: Christoph
authors.initials: C
authors.lastname: Lange
authors.affiliation: Global Tuberculosis Program, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, United States.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Mandalakas
authors.affiliation: Division of Clinical Infectious Diseases, Medical Clinic Research Center Borstel, Borstel, Germany; German Center for Infection Research (DZIF), Clinical Tuberculosis Center, Borstel, Germany; International Health/Infectious Diseases, University of Lübeck, Lübeck, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Kalsdorf
authors.affiliation: FIND, Geneva, Switzerland.
authors.forename: Claudia M
authors.initials: CM
authors.lastname: Denkinger
authors.affiliation: Department of Transplant and Infection Immunology, Saarland University, Homburg, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Sester
keywords: IGRAs; Interferon-γ release assays; M. tuberculosis; QuantiFERON; T-SPOT.TB; immunodeficiency; number needed to treat; risk groups; tuberculin skin test; tuberculosis