Comparison of Tuberculin Skin Test and New Specific Blood Test in Tuberculosis Contacts

Abstract

The tuberculin skin test used to detect latent Mycobacterium tuberculosis infection has many drawbacks, and a new diagnostic test for latent tuberculosis (QuantiFERON-TB [QTF-TB]) has recently been introduced. This test measures the production of IFN-gamma in whole blood upon stimulation with purified protein derivative (PPD). The QTF-TB test addresses the operational problems with the tuberculin skin test, but, as the test is based on PPD, it still has a low specificity in populations vaccinated with the Bacille Calmette-Guérin (BCG) vaccine. We have modified the test to include the antigens ESAT-6 and CFP-10, which are not present in BCG vaccine strains or the vast majority of nontuberculous mycobacteria. This test was used to detect infection in contacts in a tuberculosis outbreak at a Danish high school. The majority of the contacts were BCG-unvaccinated, which allowed a direct comparison of the skin test and the novel blood test in individuals whose skin test was not confounded by vaccination. An excellent agreement between the two tests was found (94%, kappa value 0.866), and in contrast to the blood test based on PPD, the novel blood test was not influenced by the vaccination status of the subjects tested.

Evaluation of the diagnostic utility of a whole-blood interferon-γ assay for determining the risk of exposure to Mycobacterium tuberculosis in Bacille Calmette-Guerin (BCG)-vaccinated individuals

“…It has been previously reported that in vitro whole blood IFN-γ response to PPD correlates well with TST (Black et al, 2001). We found poor agreement between QuantiFERON® and PPD tests in all groups, which is consistent with other reports (Brock et al, 2001(Brock et al, & 2004Mori et al, 2004;Kang et al, 2005) and confirms that QuantiFERON® test is substantially more specific than TST in BCG vaccinated persons. Brock and co-workers (2004) showed that, in BCG-vaccinated persons, 50 % of high-exposure and 6 % of lowexposure group responded to QuantiFERON®, which gives the similar overall prevalence to those of the unvaccinated subjects, 53 % and 5 %, respectively.…”

“…TST is also likely to be a good indicator of latent infection in a population of BCG-unvaccinated subjects but is confounded by BCG vaccination (Brock et al, 2004). In the present study, we demonstrated that QuantiFERON® test kit clearly differentiated the BCG-vaccinated healthy individuals at low risk of exposure from TB patients in contrast to the results obtained using only PPD.…”

Effect of HIV-1 Infection on T-Cell–based and Skin Test Detection of Tuberculosis Infection

“…Compared with the TST, research using IFNGRA indicates a high sensitivity for active tuberculosis (8)(9)(10). Positive scores in these assays have also been shown in contact studies to equate well with a history of exposure to tuberculosis (11)(12)(13).…”

“…This was observed regardless of the cutoff point for CD4 ϩ cell count. With T-SPOT.TB, 48% (25), 54% (13), and 44% (9) at CD4 ϩ cell count Ͻ 350, Ͻ 250, and Ͻ 200/mm 3 , respectively, were identified as positive and QFT-G identified 33% (24), 33% (12), and 26%, respectively (Figure 4). Tests for trend were, however, not statistically significant.…”

MHC class II Tetramer Guided Detection of Mycobacterium tuberculosis‐specific CD4+ T Cells in Peripheral Blood from Patients with Pulmonary Tuberculosis

“…Conversely, HLA-DR4-restricted Ag85B epitopes may -in addition to MTB diagnosis -be useful to enumerate T cells specific for Mycobacterium ulcerans, the causative agent of Buruli ulcer [29] or M. avium intracellulare, a frequent cause for infections in immunecompromised patients. In addition, while novel assays, such as the IFN-c response assay (IGRA) [27,[30][31][32], address some of the weaknesses of the TST by using specific antigens in peptide form, they do not allow the simultaneous analysis of T-cell responses and T-cell marker analysis associated with T-cell homing and differentiation, as is demonstrated here. The use of a broader panel of MTB-and MOTT-associated antigens may aid in dissecting the precise targets of CD4-and CD8-mediated immune responses in MTB patients undergoing therapy (and therefore, potentially alterations in bacterial load).…”