Improved sensitivity of an interferon-gamma release assay (T-SPOT.TB™) in combination with tuberculin skin test for the diagnosis of latent tuberculosis in the presence of HIV co-Infection

Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Switzerland.
BMC Infectious Diseases (Impact Factor: 2.61). 11/2011; 11(1):319. DOI: 10.1186/1471-2334-11-319
Source: PubMed


Interferon-gamma release assays (IGRA) are more specific than the tuberculin skin test (TST) for the diagnosis of Mycobacterium tuberculosis infection. Data on sensitivity are controversial in HIV infection.
IGRA (T-SPOT.TB) was performed using lymphocytes stored within 6 months before culture-confirmed tuberculosis was diagnosed in HIV-infected individuals in the Swiss HIV Cohort Study.
64 individuals (69% males, 45% of non-white ethnicity, median age 35 years (interquartile range [IQR] 31-42), 28% with prior AIDS) were analysed. Median CD4 cell count was 223 cells/μl (IQR 103-339), HIV-RNA was 4.7 log10 copies/mL (IQR 4.3-5.2). T-SPOT.TB resulted positive in 25 patients (39%), negative in 18 (28%) and indeterminate in 21 (33%), corresponding to a sensitivity of 39% (95% CI 27-51%) if all test results were considered, and 58% (95% CI 43-74%) if indeterminate results were excluded. Sensitivity of IGRA was independent of CD4 cell count (p = 0.698). Among 44 individuals with available TST, 22 (50%) had a positive TST. Agreement between TST and IGRA was 57% (kappa = 0.14, p = 0.177), and in 34% (10/29) both tests were positive. Combining TST and IGRA (at least one test positive) resulted in an improved sensitivity of 67% (95% CI 52-81%). In multivariate analysis, older age was associated with negative results of TST and T-SPOT.TB (OR 3.07, 95% CI 1,22-7.74, p = 0.017, per 10 years older).
T-SPOT.TB and TST have similar sensitivity to detect latent TB in HIV-infected individuals. Combining TST and IGRA may help clinicians to better select HIV-infected individuals with latent tuberculosis who qualify for preventive treatment.

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    • "The T-SPOT.TB is thought to be less susceptible to this effect as the number of peripheral mononuclear cells in the assay is standardised. Studies to date of one or both IGRAs for the diagnosis of latent tuberculosis in HIV infected individuals have shown conflicting results regarding the impact of low CD4+ T-cell counts on the tests: a number of studies from high and low TB prevalence regions have found that the sensitivity of the QFT-IT and earlier versions of the Quantiferon, but not T-SPOT.TB is impaired in those with advanced immunosuppression [17], [18], [19], [20]; however, another study from a region of low TB prevalence observed that T-SPOT.TB but not QFT-IT sensitivity was impaired in those with low CD4+ T-cell counts [21]. A number of recent metanalyses found that HIV-associated immunosuppression, measured as CD4+ T-cell count, negatively affects the performance of QFT-IT, and to a lesser extent, T-SPOT.TB [22], [23]. "
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    ABSTRACT: Interferon gamma release assays (IGRAs) are used to diagnose latent tuberculosis infection. Two IGRAs are commercially available: the Quantiferon TB Gold In Tube (QFT-IT) and the T-SPOT.TB. There is debate as to which test to use in HIV+ individuals. Previous publications from high TB burden countries have raised concerns that the sensitivity of the QFT-IT assay, but not the T-SPOT.TB, may be impaired in HIV+ individuals with low CD4+ T-cell counts. We sought to compare the tests in a low TB burden setting. T-SPOT.TB, QFT-IT, and tuberculin skin tests (TST) were performed in HIV infected individuals. Results were related to patient characteristics. McNemar's test, multivariate regression and correlation analysis were carried out using SPSS (SPSS Inc). 256 HIV infected patients were enrolled in the study. The median CD4+ T-cell count was 338 cells/µL (range 1-1328). 37 (14%) patients had a CD4+ T-cell count of <100 cells/µL. 46/256 (18% ) of QFT-IT results and 28/256 (11%) of T-SPOT.TB results were positive. 6 (2%) of QFT-IT and 18 (7%) of T-SPOT.TB results were indeterminate. An additional 9 (4%) of T-SPOT.TB results were unavailable as tests were not performed due to insufficient cells or clotting of the sample. We found a statistically significant association between lower CD4+ T-cell count and negative QFT-IT results (OR 1.055, p = 0.03), and indeterminate/unavailable T-SPOT.TB results (OR 1.079, p = 0.02). In low TB prevalence settings, the QFT-IT yields more positive and fewer indeterminate results than T-SPOT.TB. Negative results on the QFT-IT and indeterminate/unavailable results on the T-SPOT.TB were more common in individuals with low CD4+ T-cell counts.
    Full-text · Article · Jan 2013 · PLoS ONE
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    • "Sputum smear provides rapid results and is widely used in clinical laboratories, but this conventional method shows low sensitivity. PCR-based nucleic acid amplification assays and Immunological tests brought great progress in TB rapid diagnostics [4-8]. However, endogenous amplification inhibition factor of M. tuberculosis or unreliable quality control resulting in both false positives and negatives have hampered the clinical use of PCR assays. "
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    ABSTRACT: Background Pulmonary tuberculosis (TB) is a highly lethal infectious disease and early diagnosis of TB is critical for the control of disease progression. The objective of this study was to profile a panel of serum microRNAs (miRNAs) as potential biomarkers for the early diagnosis of pulmonary TB infection. Methods Using TaqMan Low-Density Array (TLDA) analysis followed by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) validation, expression levels of miRNAs in serum samples from 30 patients with active tuberculosis and 60 patients with Bordetella pertussis (BP), varicella-zoster virus (VZV) and enterovirus (EV) were analyzed. Results The Low-Density Array data showed that 97 miRNAs were differentially expressed in pulmonary TB patient sera compared with healthy controls (90 up-regulated and 7 down-regulated). Following qRT-PCR confirmation and receiver operational curve (ROC) analysis, three miRNAs (miR-361-5p, miR-889 and miR-576-3p) were shown to distinguish TB infected patients from healthy controls and other microbial infections with moderate sensitivity and specificity (area under curve (AUC) value range, 0.711-0.848). Multiple logistic regression analysis of a combination of these three miRNAs showed an enhanced ability to discriminate between these two groups with an AUC value of 0.863. Conclusions Our study suggests that altered levels of serum miRNAs have great potential to serve as non-invasive biomarkers for early detection of pulmonary TB infection.
    Full-text · Article · Dec 2012 · BMC Infectious Diseases

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