Abstract
Interferon-gamma (IFN-γ) release assays (IGRAs) such as the Quantiferon Gold In-tube test are in vitro assays that measure IFN-γ release from T cells in response to M. tuberculosis (Mtb)-specific antigens. Unlike the tuberculin skin test (TST), IGRA is specific and able to distinguish Mtb-infection from BCG vaccination. In this study we evaluated the concordance between TST and IGRA and the efficacy of IGRA in diagnosing new Mtb infection in household contacts (HHC) of pulmonary tuberculosis (PTB) cases. A total of 357 HHC of TB cases in Vitória, Brazil were studied. A TST was performed within 2 weeks following enrollment of the HHC and if negative a second TST was performed at 8-12 weeks. HHC were categorized as initially TST positive (TST+), persistently TST negative (TST-), or TST converters (TSTc), the latter representative of new infection. IGRA was performed at 8–12 weeks following enrollment and the test results were positive in 82% of TST+, 48% of TSTc, and 12% of TST-, indicating poor concordance between the two test results among HHC in each category. Evaluating CXCL10 levels in a subset of IGRA supernatants or lowering the IGRA cutoff value to define a positive test increased agreement between TST and IGRA test results. However, ROC curves demonstrated that this resulted in a trade-off between sensitivity and specificity of IGRA with respect to TST. Together, the findings suggest that until the basis for the discordance between TST and IGRA is fully understood, it may be necessary to utilize both tests to diagnose new Mtb infection in recently exposed HHC. Operationally, in IGRA negative HHC, it may be useful to employ a lower cutoff value for IGRA to allow closer monitoring for potential conversion.
Highlights
Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is still a major human health problem, especially in developing countries
The aim of this study was to determine the performance of Interferon-gamma (IFN-c) release assays (IGRAs) compared to TST in recently exposed HHC as part of a larger International Collaboration in Infectious Diseases Research (ICIDR) study designed to investigate the extent of Mtb transmission in HHC exposed to an index case (IC) with infectious pulmonary TB (PTB)
Of the 467 HHC enrolled in the ICIDR study by the cutoff date, 110 participants could not be included in the analysis because: a) one had active TB disease; b) four had no TST and IGRA testing; c) nine had no TST testing; d) one had a week 8–12 TST but no initial TST; e) twenty-three were TST negative at week 1–2 but had no repeat TST at week 8–12; f) seventy-one had no IGRA testing; and g) one had an indeterminate IGRA result
Summary
Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is still a major human health problem, especially in developing countries. The World Health Organization estimated that there were 8.8 million new cases of TB (12% co-infected with HIV) and 1.34 million people died from TB in 2012 [1]. In latent tuberculosis infection (LTBI), the mycobacteria persist and can reactivate at a later time to cause active disease in about 10% of those infected over a lifetime (HIV uninfected). A major challenge in TB control is to be able to diagnose, predict, and treat those with LTBI before they develop active disease. In order to assess the predictive utility of diagnostic tests for LTBI, long-term follow-up of individuals from infection to disease is required
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