Agreement between QuantiFERON®-TB Gold In-Tube and the tuberculin skin test and predictors of positive test results in Warao Amerindian pediatric tuberculosis contacts.

Lilly M Verhagen,Lazaro Perez Rodriguez,Julian A Villalba,Adriana D’Alessandro,Jacobus H De Waard,Mercedes F España,Peter Wm Hermans,Mailis Maes

doi:10.1186/1471-2334-14-383

Abstract

BackgroundInterferon-gamma release assays have emerged as a more specific alternative to the tuberculin skin test (TST) for detection of tuberculosis (TB) infection, especially in Bacille Calmette-Guérin (BCG) vaccinated people. We determined the prevalence of Mycobacterium tuberculosis infection by TST and QuantiFERON®-TB Gold In-Tube (QFT-GIT) and assessed agreement between the two test methods and factors associated with positivity in either test in Warao Amerindian children in Venezuela. Furthermore, progression to active TB disease was evaluated for up to 12 months.Methods163 HIV-negative childhood household contacts under 16 years of age were enrolled for TST, QFT-GIT and chest X-ray (CXR). Follow-up was performed at six and 12 months. Factors associated with TST and QFT-GIT positivity were studied using generalized estimation equations logistic regression models.ResultsAt baseline, the proportion of TST positive children was similar to the proportion of children with a positive QFT-GIT (47% vs. 42%, p = 0.12). Overall concordance between QFT-GIT and TST was substantial (kappa 0.76, 95% CI 0.46-1.06). Previous BCG vaccination was not associated with significantly increased positivity in either test (OR 0.68, 95% CI 0.32-1.5 for TST and OR 0.51, 95% CI 0.14-1.9 for QFT-GIT). Eleven children were diagnosed with active TB at baseline. QFT-GIT had a higher sensitivity for active TB (88%, 95% CI 47-98%) than TST (55%, 95% CI 24-83%) while specificities were similar (respectively 58% and 55%). Five initially asymptomatic childhood contacts progressed to active TB disease during follow-up.ConclusionReplacement of TST by the QFT-GIT for detection of M. tuberculosis infection is not recommended in this resource-constrained setting as test results showed substantial concordance and TST positivity was not affected by previous BCG vaccination. The QFT-GIT had a higher sensitivity than the TST for the detection of TB disease. However, the value of the QFT-GIT as an adjunct in diagnosing TB disease is limited by a high variability in QFT-GIT results over time.

Highlights

Interferon-gamma release assays have emerged as a more specific alternative to the tuberculin skin test (TST) for detection of tuberculosis (TB) infection, especially in Bacille Calmette-Guérin (BCG) vaccinated people
At baseline 163 household contacts were enrolled for TST testing, QuantiFERON®-TB Gold In-Tube (QFT-GIT) and chest X-ray (CXR) (Figure 1)
The concordance between TST and QFT-GIT was lower but still substantial in BCG vaccinated children compared with children who were not BCG vaccinated (ĸ 0.74, 95% confidence intervals (CI) 0.62-0.86 vs. ĸ 0.89, 95% CI 0.68-1.09 respectively)

Summary

Introduction

Interferon-gamma release assays have emerged as a more specific alternative to the tuberculin skin test (TST) for detection of tuberculosis (TB) infection, especially in Bacille Calmette-Guérin (BCG) vaccinated people. A unique aspect of TB in young children is the rapid progression to disease, typically within the first year following infection, unlike in adults, where latent TB infection (LTBI) can persist for decades without progression into active disease [2]. The tuberculin skin test (TST) is a simple and relatively cheap test for the detection of LTBI. The specificity of the TST is affected by cross-reactivity with the Bacille Calmette-Guérin (BCG) vaccine and exposure to nontuberculous mycobacteria [3]. Interferon-gamma release assays (IGRAs) have emerged as a more specific alternative to the TST [4]

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