Abstract
BackgroundSmear-negative pulmonary tuberculosis (TB) accounts for a considerable proportion of TB transmission, which especially endangers health care workers (HCW). Novel Mycobacterium-tuberculosis-specific interferon-γ release assays (IGRAs) may offer the chance to define the burden of TB in HCW more accurately than the Mantoux tuberculin skin test (TST), but the data that is available regarding their performance in tracing smear-negative TB in the low-incidence, in-hospital setting, is limited. We conducted a large-scale, in-hospital contact investigation among HCW of a German university hospital after exposure to a single case of extensive smear-negative, culture-positive TB with pulmonary involvement. The objective of the present study was to evaluate an IGRA in comparison to the TST and to identify risk factors for test positivity.MethodsContacts were prospectively enrolled, evaluated using a standardized questionnaire, the IGRA QuantiFERON®-TB Gold in Tube (QFT-GIT) and the TST, and followed-up for two years. Active TB was ruled out by chest x-ray in QFT-GIT-positive subjects. Independent predictors of test positivity were established through the use of logistic regression analysis.ResultsOut of the 143 subjects analyzed, 82 (57.3%) had close contact, but only four (2.8%) experienced cumulative exposure to the index case >40 hours. QFT-GIT results were positive in 13 subjects (9.1%), while TST results were positive in 40 subjects (28.0%) at an induration >5 mm. Overall agreement was poor between both tests (kappa = 0.15). Age was the only predictor of QFT-GIT-positivity (Odds ratio 2.7, 95% confidence interval 1.32–5.46), while TST-positivity was significantly related to Bacillus Calmette-Guérin vaccination and foreign origin. Logistic regression analysis showed no relation between test results and exposure. No secondary cases of active TB were detected over an observational period of two years.ConclusionOur findings suggest a low contagiosity of the particular index case. The frequency of positive QFT-GIT results may in fact reflect the pre-existing prevalence of latent TB infection among the study population. TB transmission seems unlikely and contact tracing not generally warranted after cumulative exposure <40 hours. However, the substantially lower frequency of positive QFT-GIT results compared to the TST may contribute to enhanced TB control in health care.
Highlights
Smear-negative pulmonary tuberculosis (TB) accounts for a considerable proportion of TB transmission, which especially endangers health care workers (HCW)
They are broadly recommended and increasingly used in contact investigations [5,6], as they provide distinct advantages over the TST. Their sensitivity for detecting active TB, which is commonly used as a surrogate for latent TB infection (LTBI), is at least equal and their specificity is clearly superior, at least in populations that contain a proportion of Bacillus Calmette-Guérin (BCG)-vaccinated individuals, as they are not confounded by BCG vaccination
The aim of the present study was to compare the performance of the IGRA QuantiFERON®-TB Gold in Tube (QFT-GIT) with the Mantoux tuberculin skin test (TST) in a large-scale inhospital contact investigation among German HCW after exposure to a single case of smear-negative, culture-positive pulmonary TB and to identify independent risk factors of test positivity
Summary
Smear-negative pulmonary tuberculosis (TB) accounts for a considerable proportion of TB transmission, which especially endangers health care workers (HCW). In-vitro interferon-γ release assays (IGRAs) that measure the amount of interferon-(IFN)-γ secreted by T-cell lymphocytes after stimulation with highly Mycobacterium-tuberculosis-(MTB)-specific antigens have been developed as alternative diagnostics They are broadly recommended and increasingly used in contact investigations [5,6], as they provide distinct advantages over the TST. Their sensitivity for detecting active TB, which is commonly used as a surrogate for LTBI, is at least equal and their specificity is clearly superior, at least in populations that contain a proportion of BCG-vaccinated individuals, as they are not confounded by BCG vaccination. They are appropriate for the serial testing of health care workers (HCW) as they avoid boosting of immune responses and possess distinct logistical conveniences [7,8,9]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
