ReviewRole of interferon-gamma release assays in healthcare workers
Introduction
Since the nineteenth century the tuberculin skin test (TST) has been used to detect a response to tuberculous antigens. However, weaknesses of the TST include intra-observer variation in its interpretation, false-positive results related to Bacille Calmette–Guérin (BCG) vaccination or non-tuberculous mycobacteria (NTM), and a ‘boosting’ phenomenon if used repeatedly. The patient must also attend on two separate occasions: initially for the test to be administered, and again for the result to be read. There is also wide variation in global practice regarding administration and interpretation of the TST.
The recent development of the interferon-gamma release assay (IGRA) provides a potential opportunity to overcome many of these problems. IGRAs are performed on venous blood samples and measure interferon-gamma (IFN-γ) production by T-cells following exposure to tuberculous antigens in vitro. Early versions used PPD to stimulate T-cells; specificity has since been improved by using antigens, such as the early secreted antigenic target 6 (ESAT-6) and culture filtrate protein 10 (CFP 10) encoded within the region of difference (RD-1) on the Mycobacterium tuberculosis chromosome. Following antigenic stimulation, IFN-γ production is either measured by enzyme-linked immunosorbent assay (ELISA) or enzyme-linked immunosorbent spot (ELISPOT) techniques. Two forms of IGRA are commercially available: the ELISA method is incorporated into the QuantiFERON®-TB (QFT) test (Cellestis Ltd, Carnegie, Australia), whereas the T-SPOT®.TB test (Oxford Immunotec, Oxford, UK) uses the ELISPOT procedure.1 A simplified QFT test (QuantiFERON-TB Gold In-Tube assay) containing ESAT-6, CFP 10 and a portion of tuberculosis antigen TB7.7 (Rv2654) was introduced in 2007.
It is estimated that up to one-third of the world's population has latent tuberculosis infection (LTBI) and up to 10% of LTBI cases may subsequently develop active disease.2 The inadequacies of the TST for diagnosing LTBI present a major challenge to the control of tuberculosis (TB).3
Diagnosing LTBI among healthcare workers (HCWs) presents an even greater challenge: although HCWs are at greater risk of infection with M. tuberculosis,4 BCG vaccination is commonplace, and the boosting phenomenon of repeated TSTs complicates their use as a routine screening tool.
This review seeks to summarise the available evidence for the utility of IGRA among HCWs in different settings, to compare their performance with TSTs and to highlight areas where unanswered questions remain for future research.
Section snippets
Study selection and data abstraction
We searched PubMed using the terms (health care* OR healthcare* OR health care worker OR doctors OR physician* OR Nurse* OR medical staff) AND (tuberculosis or TB) AND (quantiferon* OR elispot OR IFN* OR interferon* OR IFN-γ assays OR IFN-γ release assays OR t cell assays OR ESAT-6 OR CFP10 OR rd1 antigens) for studies published between 1 January 1990 and 7 September 2008 that reported data on IGRAs in HCWs. We identified additional studies from the reference lists of articles. Studies
Results
Of the 82 studies identified, 29 were considered suitable for inclusion and full text articles were obtained. After excluding seven non-English language studies, a total of 22 articles were included in this review (Figure 1).
Two papers incorporated the T-SPOT.TB test, one of which compared the QFT with the T-SPOT.TB test.5, 6 The other 20 studies only examined the characteristics of the QFT. Four studies presented data from contact investigations, and one incorporated HCWs undergoing either
Discussion
This review found poor levels of agreement between TST and QFT among HCWs. However, IGRAs showed greater correlation with TB exposure. Studies undertaken in countries where the estimated annual incidence of TB was ≤20 per 100 000 per year unanimously concluded that there was poor agreement between the QFT and TST, and found a predominant pattern of positive TST and negative QFT where the two tests were discordant.7, 9, 10, 11, 12, 13, 14, 15, 26 By contrast, two studies of HCWs in countries
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Cited by (17)
Unmasking leading to a healthcare worker Mycobacterium tuberculosis transmission
2018, Journal of Hospital InfectionCitation Excerpt :In this outbreak, the majority of contact tracing involved the use of IGRA. Swindells et al. undertook a systematic review of the usefulness of IGRA for the detection of LTBI in HCWs [17]. HCWs are at highest risk of TB infection but have often been vaccinated; Swindells et al. showed how IGRAs correlated better with markers of exposure to TB including during contact investigation [17].
Cost-effectiveness of interferon-gamma release assay for systematic tuberculosis screening of healthcare workers in low-incidence countries
2015, Journal of Hospital InfectionCitation Excerpt :Delays in TB diagnosis and treatment among HCWs result in costly large-scale TB contact screening among patients and other HCWs. Interferon-gamma release assays (IGRAs) for TB screening have improved specificity compared with TST, and allow more focused targeting of preventive therapy; as such, fewer HCWs receive prophylaxis inappropriately.3 The US Centers for Disease Control and Prevention recommend that every healthcare setting should have a TB infection control plan that is part of an overall infection control programme based on risk assessment.4,5
Safety of the two-step tuberculin skin test in Indian health care workers
2014, International Journal of MycobacteriologyCitation Excerpt :Furthermore, IGRAs are in vitro tests and eliminate concerns regarding adverse events or boosting and do not require a return visit [1,8,16–18]. The use of IGRAs for HCWs is increasing and there are several published studies and two systematic reviews published [8,19–21]. While these assays show promise for screening in low incidence settings, they appear to have a lower sensitivity in high incidence settings such as India [8,16,19].