Interferon-gamma release assays for tuberculosis screening of healthcare workers: a systematic review
- Alice Zwerling1,
- Susan van den Hof2,3,
- Jerod Scholten2,
- Frank Cobelens2,3,
- Dick Menzies1,
- Madhukar Pai1
- 1McGill University and Montreal Chest Institute, Montreal, Canada
- 2KNCV Tuberculosis Foundation, The Hague, The Netherlands
- 3Center 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
- Correspondence to Madhukar Pai, Department of Epidemiology, Biostatistics and Occupational Health, McGill University, 1020 Pine Avenue West, Montreal H3A 1A2, Canada;
- Received 25 May 2010
- Accepted 2 December 2010
- Published Online First 12 January 2011
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 (n=2) 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.
The findings of this review were presented at a WHO Expert Group Meeting on interferon-gamma release assays in July 2010 organised by the Stop TB Department of the WHO.
Funding This work was supported in part by USAID funding through TB CAP, the Canadian Institutes of Health Research (grant MOP-81362) and the Special Programme for Research and Training in Tropical Diseases (TDR). These agencies had no role in the design, execution or publication of this study. AZ is supported by a Canadian Institutes of Health Research (CIHR) doctoral research award. MP is a recipient of a CIHR New Investigator Award and DM is a recipient of a Fonds de la recherche en santé du Québec (FRSQ) career award.
Competing interests No financial conflicts. At the time this review was conducted MP served as an external consultant for the Foundation for Innovative New Diagnostics (FIND), Geneva, a non-profit agency that works with several industry partners including Cellestis Ltd, Australia in developing and evaluating new diagnostic tools for neglected diseases.
Provenance and peer review Not commissioned; externally peer reviewed.