Guidelines on interferon-γ release assays for tuberculosis infection: concordance, discordance or confusion?


  • C. M. Denkinger,

    1.  Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA
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  • K. Dheda,

    1.  Lung Infection and Immunity Unit, Division of Pulmonology and UCT Lung Institute, Department of Medicine, University of Cape Town, Cape Town, South Africa
    2.  Department of Infection, University College London Medical School, London, UK
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  • M. Pai

    1.  Department of Epidemiology, Biostatistics, and Occupational Health, McGill University
    2.  Respiratory Epidemiology and Clinical Research Unit, Montreal Chest Institute, Montreal, QC, Canada
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Corresponding author: M. Pai, Department of Epidemiology and Biostatistics, McGill University, 1020 Pine Ave West, Montreal, QC, Canada H3A 1A2


Clin Microbiol Infect 2011; 17: 806–814


Identification of latent tuberculosis (TB) infection and preventive therapy is important for TB control, especially in high-risk populations. Since the advent of interferon-γ release assays (IGRAs), many studies have evaluated their role in the diagnosis of active and latent TB. With the growing evidence base, many guidelines now include IGRAs. We surveyed the literature and contacted experts to identify 33 guidelines and position papers from 25 countries and two supranational organizations. The results show considerable diversity in the recommendations on IGRAs, with four approaches commonly proposed: (i) two-step approach of tuberculin skin test (TST) first, followed by IGRA either when the TST is negative (to increase sensitivity, mainly in immunocompromised individuals), or when the TST is positive (to increase specificity, mainly in bacillus Calmette–Guérin-vaccinated individuals); (ii) Either TST or IGRA, but not both; (iii) IGRA and TST together (to increase sensitivity); and (iv) IGRA only, replacing the TST. Overall, the use of IGRAs is increasingly recommended, but most of the current guidelines do not use objective, transparent methods to grade evidence and recommendations, and do not disclose conflicts of interests. Future IGRA guidelines must aim to be transparent, evidence-based, periodically updated, and free of financial conflicts and industry involvement.