Prospective evaluation of latent tuberculosis with interferon-γ release assays in drug and alcohol abusers

Department of Internal Medicine, Hospital Universitari Germans Trias i Pujol, Badalona, Spain.
Epidemiology and Infection (Impact Factor: 2.54). 03/2009; 137(9):1342-7. DOI: 10.1017/S0950268809002131
Source: PubMed


In vitro tests have been developed for the diagnosis of tuberculosis (TB) infection. The objective was to analyse latent TB infection in drug and alcohol abusers through two interferon-gamma techniques. One hundred and thirty-nine patients were admitted between February 2006 and May 2007. Mean age was 39.8 years [31% HIV positive]. The enzyme immunoassay (EIA) and enzyme-linked immunospot (ELISPOT) interferon-gamma assays were positive in 34% of patients with an agreement of 83% (kappa=0.63). Tuberculin skin test (TST) was positive in 29% of patients and the agreement of TST with EIA and ELISPOT interferon-gamma assays was 85% (kappa=0.62) and 83% (kappa=0.57), respectively. Almost 50% of patients with history of TB had a positive in vitro test. In conclusion, we observed a high prevalence of latent TB and good agreement between the new in vitro tests that otherwise may continue to be positive long after developing TB disease.

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    • "3 M. Nikolova et al. / Diagnostic Microbiology and Infectious Disease xxx (2012) xxx–xxx Please cite this article as: Nikolova M, et al, Antigen-specific CD4-and CD8-positive signatures in different phases of Mycobacterium tuberculosis infection, Diagn Microbiol Infect Dis (2012), The QFT-IT assay includes as antigens overlapping optimized peptides of the well-characterized RD1 proteins ESAT-6 (Rv3875) and CFP-10 (Rv3874), and of antigen 7.7 (Rv2645) belonging to RD11 (Rivas et al., 2009). It is well known that ESAT-6 and CFP-10 contain both CD4+-and CD8+-restricted epitopes (Shams et al., 2004; Wang et al., 2010). "
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    ABSTRACT: Current diagnostic standards for Mycobacterium tuberculosis (MTB) infection do not distinguish between active and latent tuberculosis (TB). To identify specific biomarkers characterizing the different forms of TB infection, we investigated in parallel with the QuantiFERON -TB Gold In-Tube (QFT-IT) the use of flow cytometry measuring CD4 and CD8 MTB-specific immune response in 17 active-TB patients, 21 health care workers (HCW), 14 recent contacts of TB patients (RC-TB), and 10 bacille Calmette Guerin (BCG)-vaccinated healthy controls (BCG-HC). A correlation (r = 0.4526, P = 0.0002) was found only between the amount of IFN-γ measured by QFT-IT and the frequency of CD4+/CD69+/IFN-γ+ T cells. The frequency of CD4+/CD69+/IFNγ+ responding T cells was higher in active-TB patients (0.254 ± 0.336%, P < 0.01) compared to the other groups. The response of QFT-IT antigen-specific CD8+/CD69+/IFNγ+ T cells was significantly higher in RC-TB (0.245 ± 0.305%, P < 0.05) compared to the other study groups.
    Diagnostic microbiology and infectious disease 12/2012; 75(3). DOI:10.1016/j.diagmicrobio.2012.11.023 · 2.46 Impact Factor
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    • "It has been demonstrated in the majority of the studies, that IFN-γ assays have higher number of positive results than TST and a poor agreement with it [19-21,23,30-34]. Nevertheless, only a few studies have performed a direct comparison of T-SPOT.TB, QFN-G-IT and TST to ascertain LTBI in HIV-positive individuals [24-27]. "
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    ABSTRACT: Individuals infected with human immunodeficiency virus (HIV) have an increased risk of progression to active tuberculosis following Mycobacterium tuberculosis infection. The objective of the study was to determine IFN-γ responses for the detection of latent tuberculosis infection (LTBI) with QuantiFERON-TB GOLD In Tube (QFT-G-IT) and T-SPOT.TB in HIV patients, and evaluate the influence of CD4 cell count on tests performance. We studied 75 HIV patients enrolled for ongoing studies of LTBI with T-SPOT.TB, QFN-G-IT and TST. Mean CD4 cell counts ± standard deviation was 461.29 ± 307.49 cells/μl. Eight patients had a BCG scar. T-SPOT.TB, QFN-G-IT and TST were positive in 7 (9.3%), 5 (6.7%) and 9 (12%) cases, respectively. Global agreement between QFN-G-IT and T-SPOT.TB was 89% (κ = 0.275). The overall agreement of T-SPOT.TB and QFN-G-IT with TST was 80.8% (κ = 0.019) and 89% (κ = 0.373), respectively. We have found negative IFN-γ assays results among 2 BCG-vaccinated HIV-infected individuals with a positive TST. In non BCG-vaccinated patients, QFN-G-IT and TST were positive in 5 cases (7.5%) and T-SPOT.TB in 7 (10.4%). In contrast, in BCG-vaccinated patients, only TST was positive in 4/8 (50%) of the cases. The differences obtained in the number of positive results between TST and both IFN-γ assays in BCG vaccinated patients were significant (95% CI 3-97%, p = 0.046), however, the confidence interval is very wide given the small number of patients. In patients with CD4< 200, we obtained only one (5%) positive result with T-SPOT.TB; however, QFN-G-IT and TST were negative in all cases. On the contrary, percentages of positive results in patients with CD4> 200 were 10.9% (6/55), 9.1% (5/55) and 16.4% (9/55) with T-SPOT.TB, QFN-G-IT and TST, respectively. IFN-γ tests have the benefit over TST that are less influenced by BCG vaccination, consequently they are more specific than TST. Although our number of patients with advance immunosuppression is limited, our study suggests that IFN-γ assays are influenced with level of immunosuppression. The use of IFN-γ assays could be a helpful method for diagnosing LTBI in HIV population.
    BMC Infectious Diseases 12/2010; 10(1):348. DOI:10.1186/1471-2334-10-348 · 2.61 Impact Factor
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    ABSTRACT: To evaluate the interferon-gamma-releasing assays QuantiFERON-tuberculosis (TB) Gold and T-SPOT.TB in addition to tuberculin skin test (TST) for diagnosis of latent tuberculosis infection in HIV patients. Prospective cross-sectional study for asymptomatic HIV-infected outpatients from a large University hospital. Simultaneous performance of QuantiFERON-TB Gold, T-SPOT.TB and TST. Incidence and risk factors for a positive test reaction and the concordance (kappa) between the tests were investigated. Of 286 enrolled patients, 81% were men; median age was 44 years, the median CD4 cell count 408/microl (range 7-1510) with a median nadir of 126/microl (range 0-749). A number of patients (63.8%) had undetectable HIV RNA (<50 copies/ml). Both T-SPOT.TB and QuantiFERON-TB showed more positive test results than TST: 25.2 and 20.0% (P = 0.133) compared with 12.8% (P < 0.001 and P = 0.008, respectively). Agreement between T-SPOT.TB and TST (kappa = 0.201) respectively QuantiFERON-TB and TST (kappa = 0.335) was fair, but only poor between the serological assays (kappa = 0.146). T-SPOT.TB provided more indeterminate results than QuantiFERON-TB (8 vs. 1/256, P < 0.01). Patients with a positive QuantiFERON-TB result had higher median CD4 cell counts (457 vs. 405 cells/microl for patients with negative result, P = 0.044); the amount of released interferon-gamma correlated with CD4 cell counts (rho = 0.199; P < 0.002). T-SPOT.TB results were independent from CD4 cell counts. In HIV-infected patients from a low prevalence TB country, both interferon-gamma assays are more sensitive than TST, but seem to be less sensitive than in immunocompetent patients. The blood tests show poor agreement and differ in their dependence on the CD4 cell count.
    AIDS (London, England) 12/2008; 22(18):2471-9. DOI:10.1097/QAD.0b013e3283188415 · 5.55 Impact Factor
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