THORAXJNL143180 62..70

Healthcare workers (HCWs) are at increased risk of exposure to tuberculosis (TB). Traditionally, screening for latent TB infection (LTBI) is done using the tuberculin skin test (TST). Interferon-gamma release assays (IGRAs) are now increasingly being used for diagnosis of LTBI, but their role in HCW screening is unclear. A systematic review was conducted of all IGRA studies in HCWs to summarise their performance in cross-sectional and serial testing settings. By searching four electronic databases and other sources, all available studies using any one of the commercial IGRA assays in HCWs were retrieved and screened. 50 unique studies were identified which met the inclusion criteria including five from high TB incidence settings. Among 24 cross-sectional studies in low TB incidence settings, the pooled prevalence of positive IGRA using either test was significantly lower than for a positive TST. However, in high-incidence settings (n1⁄42) there were no consistent differences in the prevalence of positive tests. IGRAs showed good correlation with occupational risk factors for TB exposure in low-incidence settings. Only 10 studies assessed use of IGRA for serial testing and all showed large variation in the rates of conversions and reversions, with no data suggesting that IGRAs are better at identifying the incidence of new TB infection than the TST. The use of IGRAs instead of TST for one-time screening may result in a lower prevalence of positive tests and fewer HCWs who require LTBI treatment, particularly in low TB incidence settings. However, the use of IGRAs for serial testing is complicated by lack of data on optimum cut-offs for serial testing and unclear interpretation and prognosis of conversions and reversions. Further longitudinal research will be required to inform guidelines on serial testing using IGRAs. INTRODUCTION Tuberculosis (TB) continues to have a significant health impact worldwide with an estimated onethird of the world’s population infected with latent TB (LTBI). TB poses a significant occupational health problem and healthcare workers (HCWs) are at increased risk of exposure to TB. 2 A systematic review of 51 studies showed that the prevalence and incidence of TB infection and disease were high among HCWs in low and middle income countries. The emergence of extensively drug-resistant TB has resulted in a renewed interest and emphasis on the protection of the healthcare workforce. The World Health Organization (WHO) recently issued a policy on TB infection control (TBIC) in resourcelimited settings and is now actively promoting TBIC programmes. In many high-income countries, periodic screening of HCWs for LTBI is an important component of TBIC programmes. Traditionally, the prevalence of LTBI and incidence of new TB infection (ie, conversion) among HCWs has been estimated using the tuberculin skin test (TST), a test with known limitations. Recently, interferon-gamma release assays (IGRAs) have emerged as alternatives for the diagnosis of LTBI. Two IGRAs are commercially availabledthe QuantiFERON-TB Gold In-Tube (QFT) assay (Cellestis Ltd, Carnegie, Australia) and the T-SPOT.TB assay (Oxford Immunotec, Abingdon, UK). With the development of new national guidelines incorporating IGRAs, their use is steadily increasing. IGRAs have features that make them attractive for repeated screening: they are ex vivo blood-based tests that, in contrast to the TST, can be repeated any number of times without sensitisation or boosting, they require only one visit and do not need a baseline two-step protocol. There is strong evidence from systematic reviews that IGRAs, especially QFT, have excellent specificity that is unaffected by BCG vaccination, while the T-SPOT.TB shows improved sensitivity for activeTBover both theTSTandQFT. 12 However, reviews have suggested that IGRA performance differs in high versus low TB incidence settings, with relatively lower sensitivity in high-incidence countries. 14 Despite the substantial body of literature on IGRAs, almost all the available studies have limitationsdnamely, lack of a gold standard for LTBI, cross-sectional design, use of sensitivity and specificity as surrogates for patient-important outcomes, and lack of adequate data on predictive/prognostic value of IGRAs. In particular, data are lacking on how to interpret repeated (serial) IGRA testing results. 16 Currently, no guidelines exist on the use of IGRAs in countries with a high incidence of TB. Some guidelines from high-income low-incidence countries have not recommended IGRAs for serial testing of HCWs while others state that IGRAs may be used for serial testing of HCWs in place of the TST. 9 METHODS Our objective was systematically to review all studies using IGRA to test HCWs, including crosssectional, longitudinal and serial testing studies, to summarise their performance characteristics. Secondary objectives included (1) to compare IGRA performance in HCWs in high or low TB incidence settings; (2) to determine if IGRAs are better < Additional material and appendix tables A1 and A2 are published online only. To view these files please visit the journal online (http://thorax.bmj.com/ content/67/1.toc). McGill University and Montreal Chest Institute, Montreal, Canada KNCV Tuberculosis Foundation, The Hague, The Netherlands Center for Poverty-related Communicable Diseases, Amsterdam Institute for Global Health and Development and Center for Infection and Immunity Amsterdam, Academic Medical Center, Amsterdam, The Netherlands