Observational Study of QuantiFERON®-TB Gold In-Tube Assay in Tuberculosis Contacts in a Low Incidence Area

Emmanuel Bergot,Gérard Zalcman,Marie-Anne Salaün,Brigitte Malbruny,Romain Magnier,Eglantine Haustraete,Jean Louis Herrmann

doi:10.1371/journal.pone.0043520

Abstract

BackgroundQuantiFERON®-TB Gold in-Tube (QFT) assay is a recently developed test to assess latent tuberculosis infection in contagious tuberculosis (TB) contact subjects.To assess the QFT assay in recently exposed contacts of active tuberculosis patients in a French area with low TB incidence but high Bacille Calmette-Guerin coverage, and evaluate progression rates to TB disease.Methodology/Principal FindingsBetween January 2007 and December 2009, 687 contacts of culture-confirmed tuberculosis cases underwent the QFT assay, with tuberculin skin test (TST) in 473, and a 34 months mean follow-up. Of 687 contacts, 148 were QFT positive, while 526 were negative and 13 indeterminate. QFT was positive in 35% of individuals with TST ≥10 mm, 47.5% with TST ≥15 mm or phlyctenular, but in 21% of cases in which two-step TST (M0 and M3) remained negative. Conversely, QFT was negative in 69% of cases with two-step TST showing conversion from negative to positive. All indeterminate QFT were associated with TST induration <10 mm in diameter. For 29 QFT-positive subjects, no chemoprophylaxis was given due to medical contraindications. Of the remaining 119 QFT-positive contacts, 97accepted chemoprophylaxis (81.5%), and 79 (81.4%) completed the treatment. Two contacts progressed to TB disease: one subject was QFT positive and had declined chemoprophylaxis, while the other one was QFT negative. QFT positive predictive value for progression to TB was 1.96% (1/51) with a 99.8% (525/526) negative predictive value.Conclusions/SignificanceOur results confirm the safety of the QFT-based strategy for assessing the TB chemoprophylaxis indication, as only one contact developed TB disease out of 526 QFT-negative subjects.

Highlights

To prevent progression to active tuberculosis (TB) disease, the early diagnosis and treatment of recent TB infections were shown to be efficacious measures for identified contact individuals, leading to a good control of the TB burden, in countries with low TB incidence [1,2]
A strategy based on interferon-gamma release assays (IGRAs) results still needs to be evaluated in terms of reducing the number of prophylaxis treatments administered compared to a TST-based strategy and in terms of the progression rates to active TB disease for both IGRA positive and negative groups
Our study aimed to evaluate QuantiFERONH-TB Gold In-Tube assay in individuals who were recently exposed to index cases with contagious pulmonary TB in Basse-Normandie, an area with low TB incidence but high Bacille Calmette-Guerin (BCG) vaccine coverage (.80%) [13] and a low proportion of migrants (,5%) from high incidence countries

Summary

Introduction

To prevent progression to active tuberculosis (TB) disease, the early diagnosis and treatment of recent TB infections were shown to be efficacious measures for identified contact individuals, leading to a good control of the TB burden, in countries with low TB incidence [1,2]. Two published studies treat the issue of contacts and use of IGRA in low incidence TB areas, but their diverging results led to conflicting interpretations as to the interest of IGRAs compared with TST for predicting the progression risk to active TB in the case of a positive assay. Both studies confirmed the low risk of active TB in the case of negative IGRA [9,10]. To assess the QFT assay in recently exposed contacts of active tuberculosis patients in a French area with low TB incidence but high Bacille Calmette-Guerin coverage, and evaluate progression rates to TB disease

Methods

Results

Conclusion