Diagnostic Accuracy of Early Secretory Antigenic Target-6-Free Interferon-gamma Release Assay Compared to QuantiFERON-TB Gold In-tube

Overview

Journal Clin Infect Dis

Publisher Oxford University Press

Specialty Infectious Diseases

Date 2019 Jan 23

PMID 30668657

Citations 9

Authors

Elisa Nemes

Deborah Abrahams

Thomas J Scriba

Frances Ratangee

Alana Keyser

Lebohang Makhethe

Mzwandile Erasmus

Simbarashe Mabwe

Nicole Bilek

Virginie Rozot

Hennie Geldenhuys

Mark Hatherill

Maria D Lempicki

Line Lindebo Holm

Leah Bogardus

Ann M Ginsberg

Thomas Blauenfeldt

Bronwyn Smith

Ruth D Ellis

Andre G Loxton

Gerhard Walzl

Peter Andersen

Morten Ruhwald

Affiliations

Soon will be listed here.

Abstract

Background: Early secretory antigenic target-6 (ESAT-6) is an immunodominant Mycobacterium tuberculosis (M.tb) antigen included in novel vaccines against tuberculosis (TB) and in interferon-gamma (IFN-γ) release assays (IGRAs). Therefore, the availability of an ESAT-6-free IGRA is essential to determine M.tb infection status following vaccination with ESAT-6-containing vaccines. We aimed to qualify a recently developed ESAT-6-free IGRA and to assess its diagnostic performance in comparison to QuantiFERON-TB Gold In-tube (QFT).

Methods: Participants with different levels of M.tb exposure and TB disease were enrolled to determine the ESAT-6-free IGRA cutoff, test assay performance in independent cohorts compared to standard QFT, and perform a technical qualification of antigen-coated blood collection tubes.

Results: ESAT-6-free IGRA antigen recognition was evaluated in QFT-positive and QFT-negative South African adolescents. The ESAT-6-free IGRA cutoff was established at 0.61 IU/mL, based on receiver operating characteristic analysis in M.tb-unexposed controls and microbiologically confirmed pulmonary TB patients. In an independent cohort of healthy adolescents, levels of IFN-γ released in QFT and ESAT-6-free IGRA were highly correlated (P < .0001, r = 0.83) and yielded comparable positivity rates, 41.5% and 43.5%, respectively, with 91% concordance between the tests (kappa = 0.82; 95% confidence interval, 0.74-0.90; McNemar test P = .48). ESAT-6-free IGRA blood collection tubes had acceptable lot-to-lot variability, precision, and stability.

Conclusions: The novel ESAT-6-free IGRA had diagnostic accuracy comparable to QFT and is suitable for use in clinical trials to assess efficacy of candidate TB vaccines to prevent established M.tb infection.

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