High level of discordant IGRA results in HIV-infected adults and children

Department of Pediatrics, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106, USA.
The International Journal of Tuberculosis and Lung Disease (Impact Factor: 2.32). 04/2008; 12(4):417-23.
Source: PubMed


Tygerberg district, Western Cape Province, South Africa.
To measure the agreement of two interferon-gamma release assays (IGRAs) and the tuberculin skin test (TST) for the detection of Mycobacterium tuberculosis infection in human immunodeficiency virus (HIV) infected adults and children in a setting highly endemic for tuberculosis (TB).
Cross-sectional study.
In HIV-infected adults (n=20) and children (n=23), tests yielded discordant results, with 61% of individuals testing positive with T-SPOT.TB, 41% with TST and 28% with QuantiFERON TB Gold (QTF). In children, there was poor agreement between the TST and T-SPOT.TB (kappa [kappa]=-0.02), but moderate agreement between the TST and QTF (kappa=0.44). In adults, there was moderate agreement between the TST and T-SPOT.TB (kappa=0.43), and the TST and QTF (kappa = 0.46). In children and adults, there was fair agreement between the T-SPOT.TB and QTF (kappa=0.33). Twenty per cent of adults had >or=1 indeterminate IGRA results.
There is poor to moderate agreement between the TST and IGRAs in HIV-infected adults and children. T-SPOT.TB may have improved sensitivity for detection of M. tuberculosis infection in HIV-infected individuals compared to the QTF and the TST. In HIV-infected individuals, IGRA test properties are affected by test cut-off point and nil control responses.

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Available from: Anna Mandalakas, Jan 28, 2015
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    • "Methods (2014), 2006). In our study the percentage of the subjects with TST+/ QFT− discordance (13%) was lower compared to previous data analysis (O'Neal et al., 2009; Mandalakas et al., 2008). The TST and IGRAs are indirect tests that indicate a cellular immune response to recent or remote sensitization with mycobacterial antigens, and neither test can distinguish between individuals with LTBI, active TB or past TB. "
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    ABSTRACT: Discordant results between the interferon-gamma release assays (IGRAs) and tuberculin skin test (TST) are common in latent tuberculosis infection (LTBI). We evaluated whether the measurement of IFN-γ and interleukin (IL)-2T-cell responses, after prolonged M. tuberculosis-specific antigen stimulation, can be used as adjunctive biomarker for LTBI detection in subjects with discordant results between TST and QuantiFERON-Gold In-Tube (QFT). 196 healthcare workers were screened for LTBI and in 90 of those participants, the QFT was repeated after 18hrs, and IFN-γ/ IL-2 immune response were measured after 72hrs long-term stimulation. Of the 196 patients, 34 had positive, 155 negative, and 7 indeterminate QFT results. Discordant TST+/QFT- results were found in 29 (14.7%) patients, of whom 6 (20.6%) were Bacillus Calmette-Guerin (BCG) vaccinated. None of 23 non-BCG vaccinated subjects showed a specific IFN-γ immune response after 18hrs nor 72hrs of incubation, whereas 3/23 (13.04%) discordant subjects produced a specific long-term IL-2 response, which might reflect a LTBI status. In LTBI group (TST+/QFT+) both cytokine levels were increased after long-term in comparison to short-term stimulation. No significant long-term IFN-γ/IL-2 secretion was detected in control group (TST-/QFT-). Taken together, our data showed that the 87% of discordant patients who did not respond to the long-term assay, as controls subjects, were judged LTBI negative. The use of classic QFT and long-term IL-2 response may have a potential role to clarify the LTBI status in individuals in whom the diagnosis of LTBI is uncertain due to the discordance of the available diagnostic tests, such as TST and IGRA.
    Full-text · Article · Aug 2014 · Journal of Immunological Methods
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    • "Agreement was especially low between QFT-GIT and TSPOT (k = 0.18), which is similar to other reports [21-23]. Some studies have reported better agreement, but never surpassing moderate levels [24,25]. The reason for discordance between the two IGRAs in our patient population is unclear. "
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    ABSTRACT: Improved tests to diagnose latent TB infection (LTBI) are needed. We sought to evaluate the performance of two commercially available interferon-gamma release assays (IGRAs) compared to the tuberculin skin test (TST) for the diagnosis of LTBI and to identify risk factors for LTBI among HIV-infected individuals in Georgia, a country with high rates of TB. HIV-patients were enrolled from the National AIDS Center in Tbilisi, Georgia. After providing informed consent, each participant completed a questionnaire, had blood drawn for QuantiFERON-TB Gold in-Tube (QFT-GIT) and T-SPOT.TB testing and had a TST placed. The TST was read at 48--72 hrs with >= 5 mm induration considered positive. Between 2009--2011, 240 HIV-infected persons (66% male) with a median age of 38 years and a median CD4 count of 255 cells/mul (IQR: 124--412) had diagnostic testing for LTBI performed. 94% had visible evidence of a BCG scar. The TST was positive in 41 (17%) patients; QFT-GIT in 70 (29%); and T-SPOT.TB in 56 (24%). At least one diagnostic test was positive in 109 (45%) patients and only among 13 (5%) patients were all three tests positive. Three (1%) QFT-GIT and 19 (8%) T-SPOT.TB test results were indeterminate. The agreement among all pairs of tests was poor: QFT-GIT vs. T-SPOT.TB (kappa = 0.18, 95% CI .07-.30), QFT-GIT vs. TST (kappa = 0.29, 95% CI .16-.42), and TST vs. T-SPOT.TB (kappa = 0.22, 95% CI .07-.29). Risk factors for LTBI varied by diagnostic test and none showed associations between positive test results and well-known risk factors for TB, such as imprisonment, drug abuse and immunological status. A high proportion of HIV patients had at least one positive diagnostic test for LTBI; however, there was very poor agreement among all tests. This lack of agreement makes it difficult to know which test is superior and most appropriate for LTBI testing among HIV-infected patients. While further follow-up studies will help determine the predictive ability of different LTBI tests, improved modalities are needed for accurate detection of LTBI and assessment of risk of developing active TB among HIV-infected patients.
    Full-text · Article · Nov 2013 · BMC Infectious Diseases
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    • "Noteworthy, T-SPOT.TB was positive in many patients with a negative TST result, thus indicating that dual sequential testing with TST and IGRAs may be the optimal approach for LTBI screening in HIV-infected patients. Previous studies had shown that IGRAs have higher specificity than TST in low TB incidence settings [7,9,10,12,13,20], but did not specifically assess the contribution of IGRAs to the diagnosis of LTBI in patients with HIV infection. Therefore, this study expands upon the evaluation of IGRA and offers relevant information on its potential clinical usefulness. "
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    ABSTRACT: Background Diagnosis and treatment of latent tuberculosis infection (LTBI) is the most effective strategy to control tuberculosis (TB) among patients with HIV infection. The tuberculin skin test (TST) was the only available method to identify LTBI. The aim of the present work was to evaluate the usefulness of the interferon-gamma release assays (IGRAs): QuantiFERON-tuberculosis (TB) Gold-In-Tube test (QFG) and T-SPOT.TB for the diagnosis of LTBI in a diverse cohort of HIV-infected patients. Methods A prospective study was carried out in consecutive patients cared for in a single institution in Spain from January 2009 to October 2010. IGRAs and TST were performed simultaneously. TST induration ≥ 5 mm was considered positive. Results QFG, T-SPOT.TB and TST were performed in 373 subjects. Median CD4 cell count was 470/μl with a median nadir of 150/μl. TST, QFG and T-SPOT.TB were positive in 13.3%, 7.5% and 18.5% cases respectively. Among 277 patients with neither past or current TB nor previous treatment for LTBI and who had TST results, a positive TST result was obtained in 20 (7.2%) cases. When adding QFG results to TST, there were a total of 26 (8.6%) diagnoses of LTBI. When the results of both IGRAs were added, the number of diagnoses increased to 54 (17.9%) (incremental difference: 10.7% [95% confidence interval [CI]:5.3-16.2%] [p < 0.001]), and when both IGRAs were added, the number of diagnoses reached 56 (18.5%) (incremental difference: 11.3% [95% CI:5.7%–16.9%] [p < 0.001]). Patients with a CD4 cell count greater than 500 cells/μl and prior stay in prison were more likely to have a diagnosis of LTBI by TST and/or QFG and/or T-SPOT.TB (adjusted odds ratio [aOR]: 3.8; 95% CI, 1.4 – 9.9; and aOR: 3.3; 95% CI, 1.3 – 8.3, respectively). Conclusions IGRAs were more sensitive than TST for diagnosis of M. tuberculosis infection in HIV-infected patients. Dual sequential testing with TST and IGRAs may be the optimal approach for LTBI screening in this population.
    Full-text · Article · Jul 2012 · BMC Infectious Diseases
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