Interferon-gamma release assays for tuberculosis screening of healthcare workers: a systematic review

Abstract

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 (n¼2) 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.

Within-Subject Variability of Mycobacterium tuberculosis-Specific Gamma Interferon Responses in German Health Care Workers

“…As highlighted in a recent systematic review, the reversion of IGRA serial testing results is common among HCWs and more frequently observed than conversion (37). Our data suggest that this observation is explained by regression toward the means, a ubiquitous and inevitable, though often missed, statistical phenomenon that occurs whenever repeated measurements on the same subject are observed with random error, i.e., nonsystematic variation around a true mean (1).…”

“…Recently, systematic reviews have shown that IGRAs have excellent specificity for the diagnosis of LTBI even in Bacillus Calmette-Guérin (BCG)-vaccinated populations (8,23). Furthermore, they correlate with occupational risk factors of TB exposure in low-incidence settings (37).…”

“…Two recently published systematic reviews on the within-subject variability and performance in the serial testing of HCWs identified only 4 and 10 studies, respectively, which met the predefined eligibility criteria (33,37). Studies on reproducibility and within-subject variability were predominantly from high-incidence settings (India and South Africa) and included only small numbers of subjects (67 in total) (6,32,34).…”

Nível de exposição ao Mycobacterium tuberculosis em estudantes de medicina de uma universidade do sul de Minas

“…Dentre as vantagens, os IGRAs parecem não ser influenciados pela vacinação prévia com BCG 26 , necessidade de apenas uma visita (sem retorno para a leitura, como no TT), resultados em 24 horas, eliminação de erros de aplicação e interpretação de leitura do TT, uso de pequeno volume de sangue e ausência do efeito booster, por não expor o próprio paciente a um antígeno 27 . Zwerling et al 28 concluiram que o uso de IGRAs, ao invés do TT para uma triagem unica, pode resultar emuma prevalênciamenor deTT positivoe uma quantidade menor de profissionais de saúde que requeiram tratamento de TL, particularmente em locais onde a incidência de TB é baixa. Por outro lado, o uso de IGRAs ainda não está validado para o uso de rotina no Brasil 2 .…”

The Quantiferon®-TB Gold In-Tube Assay Detects Interferon- Release Responses to Mycobacterium Tuberculosis Antigens for Extended Periods of Time

“…These assays quantify the in vitro release of IFN-γ from T-cells stimulated with Mycobacterium tuberculosis (M. tuberculosis) antigens. The innovation, together with their prevailing employment, facilitates the early identification of atrisk individuals allowing for early intervention treatment for latent TB infection, thereby preventing the spread of TB in health care settings and communities where the TB patients reside [1,2].…”