Predictors of persistently positive Mycobacterium-tuberculosis-specific interferon-gamma responses in the serial testing of health care workers

Felix C Ringshausen,Gerhard Schultze-Werninghaus,Anja Schablon,Stephan Schlösser,Gernot Rohde,Albert Nienhaus

doi:10.1186/1471-2334-10-220

Abstract

BackgroundData on the performance of Mycobacterium-tuberculosis-specific interferon-(IFN)-γ release assays (IGRAs) in the serial testing of health care workers (HCWs) is limited. The objective of the present study was to determine the frequency of IGRA conversions and reversions and to identify predictors of persistent IGRA positivity among serially tested German HCWs in the absence of recent extensive tuberculosis (TB) exposure.MethodsIn this observational cohort-study HCWs were prospectively recruited within occupational safety and health measures and underwent a tuberculin skin test (TST) and the IGRA QuantiFERON®-TB Gold In-Tube (QFT-GIT) at baseline. The QFT-GIT was repeated 18 weeks later in the median. QFT-GIT conversions (and reversions) were defined as baseline IFN-γ < 0.35 IU/ml and follow-up IFN-γ ≥ 0.35 IU/ml (and vice versa). Predictors of persistently positive QFT-GIT results were calculated by logistic regression analysis.ResultsIn total, 18 (9.9%) and 15 (8.2%) of 182 analyzed HCWs were QFT-GIT-positive at baseline and at follow-up, respectively. We observed a strong overall agreement between baseline and follow-up QFT-GIT results (κ = 0.70). Reversions (6/18, 33.3%) occurred more frequently than conversions (3/162, 1.9%). Age and positive prior and recent TST results independently predicted persistent QFT-GIT positivity. Furthermore, the chance of having persistently positive QFT-GIT results raised about 3% with each additional 0.1 IU/ml increase in the baseline IFN-γ response (adjusted odds ratio 1.03, 95% confidence interval 1.01-1.04). No active TB cases were detected within an observational period of more than two years.ConclusionsThe QFT-GIT's utility for the application in serial testing was limited by a substantial proportion of reversions. This shortcoming could be overcome by the implementation of a borderline zone for the interpretation of QFT-GIT results. However, further studies are needed to clearly define the within-subject variability of the QFT-GIT and to confirm that increasing age, concordantly positive TST results, and the extend of baseline IFN-γ responses may predict the persistence of QFT-GIT positivity over time in serially tested HCWs with only a low or medium TB screening risk in a TB low-incidence setting.

Highlights

Data on the performance of Mycobacterium-tuberculosis-specific interferon-(IFN)-g release assays (IGRAs) in the serial testing of health care workers (HCWs) is limited
The latter mainly depended on the underlying screening risk classification, and the fact whether the respective HCW was screened according to the “infection protection act”, or the “biological agents regulation” of the German occupational safety and health (OSH) legislation, i. e. if the follow-up QuantiFERON®-TB Gold In-Tube (QFT-GIT) was performed rather short-term after participation in a recent contact investigation (e. g. 3-6 months after the baseline evaluation), or if the HCW was subject toannual routine screening according to his workplace risk (e. g. someone working in infectious diseases (ID)/TB care without recent exposure)
Exposure time had no significant impact on the subsequent test results among this subpopulation

Summary

Introduction

Data on the performance of Mycobacterium-tuberculosis-specific interferon-(IFN)-g release assays (IGRAs) in the serial testing of health care workers (HCWs) is limited. The use of the tuberculin skin test (TST) as a tool for serial testing is limited by cross-reactivity following Bacillus Calmette-Guérin (BCG) vaccination and exposure to non-tuberculous mycobacteria, nonspecific variations, and boosting [5]. In this respect, novel interferon-(IFN)-g release assays (IGRAs) provide distinct advantages. Novel interferon-(IFN)-g release assays (IGRAs) provide distinct advantages They are highly MTB-specific and not confounded in populations containing a high proportion of BCG-vaccinated individuals. Few studies cover their use in HCWs in intermediate and high burden countries [7,21,22] or general populations in high-income, low-incidence countries [13,23,24,25]

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