Search Results (14)

Background: The world health goal of eliminating tuberculosis (TB) is heavily hinged on timely and efficient diagnosis and treatment. The interferon-γ release assays (I.G.R.A.s) can diagnose Mycobacterium tuberculosis infection and offer an alternative to the centuries-old tuberculin skin test (T.S.T.). Yet there is disagreement over replacing the T.S.T. with I.G.R.A.s as a standard tool. Objective: We aim to assess the diagnostic ability of I.G.R.A.s compared with T.S.T. for detecting active TB cases. Methods: A systematic review identified relevant studies from four databases. In the diagnostic meta-analysis conducted with OpenMeta Analyst software, we calculated the sensitivity (SN) and specificity (SP) for active TB detection via I.G.R.A. and T.S.T. methods compared to TB culture. Results included pooled estimates for SN and SP with 95% confidence intervals (CI), stratified by age, immunity, I.G.R.A. type, and T.S.T. cut-off. Results: Our meta-analysis revealed that TB diagnosis using T.S.T. showed an SN of 72.4% and SP of 79.3%, while I.G.R.A. demonstrated higher accuracy with an SN of 78.9% and SP of 85.7%. Subgroup analysis by age indicated that I.G.R.A. consistently outperformed T.S.T. in both adult and pediatric populations. Among immunocompromised individuals, T.S.T. had low SN (23%) but high SP (91.2%), whereas I.G.R.A. had higher SN (65.6%) but lower SP (81.9%). Immunocompetent subjects showed that T.S.T. had SN of 72% and SP of 87.3%, while I.G.R.A. had higher SN (82.9%) and SP (89.1%). Evaluation by I.G.R.A. type revealed that T-SPOT.GIT demonstrated a higher SN but lower SP compared to QFT-GIT. Assessing T.S.T. cut-offs, SP was highest (88.8%) at ≥15 mm, while SN peaked (71.6%) at ≥5 mm. Conclusions: I.G.R.A. consistently showed higher diagnostic accuracy than T.S.T. across most studied subgroups, indicating its potential superiority in active TB diagnosis. Full article

Background and Objectives: This study aimed to evaluate the performance of a new chemiluminescent immunoassay-based tuberculosis (TB) interferon-gamma release assay (IGRA), AdvanSureI3 TB-IGRA (LG Chem Ltd., Seoul, Republic of Korea), for detecting latent tuberculosis infection in comparison with T-SPOT.TB (Oxford Immunotec, Oxford, UK). Materials and Methods: Between June 2021 and December 2021, 125 non-duplicate blood specimens were collected from adult volunteers; each subject received both tests concurrently. Total agreement and Cohen’s kappa coefficient (κ) were used to calculate concordance. The Jonckheere–Terpstra test was used to examine the correlation between interferon-gamma (IFN-γ) levels in AdvanSureI3 TB-IGRA and spot counts in T-SPOT.TB. Results: The IGRA findings of the two assays revealed 90.8% (95% confidence interval [CI] = 84.2–94.8) total agreement with κ of 0.740 (95% CI = 0.595–0.885), showing substantial agreement between the two tests. Additionally, the amount of IFN-γ in AdvanSureI3 TB-IGRA increased with the spot counts in T-SPOT.TB (p < 0.001). Conclusions: Our research revealed that the results of the AdvanSureI3 TB-IGRA were comparable to those of T-SPOT.TB. Full article

Hemodialysis (HD) patients should be screened for latent tuberculosis (TB) infection. We aimed to determine the frequency of latent TB infection in HD patients and to compare the effectiveness of the tests used. The files of 56 HD patients followed between 1 January 2021 and 1 October 2022 were retrospectively analyzed. Demographic data, the presence of the Bacillus Calmette-Guerin (BCG) vaccine, whether or not the patients had previously received treatment for TB before, the status of encountering a patient with active TB of patients over 18 years of age, without active tuberculosis and who had a T-SPOT.TB test or a Tuberculin Skin Test (TST) were obtained from the patient files. The presence of previous TB in a posterior–anterior (PA) chest X-ray was obtained by evaluating PA chest X-rays taken routinely. Of the patients, 60.7% (n = 34) were male and their mean age was 60.18 ± 14.85 years. The mean duration of dialysis was 6.43 ± 6.03 years, and 76.8% (n = 43) had 2 BCG scars. The T-SPOT.TB test was positive in 32.1% (n = 18). Only 20 patients (35.7%) had a TST and all had negative results. While the mean age of those with positive T-SPOT.TB results was higher (p = 0.003), the time taken to enter HD was shorter (p = 0.029). T-SPOT.TB test positivity was higher in the group that had encountered active TB patients (p = 0.033). However, no significant difference was found between T-SPOT.TB results according to BCG vaccine, albumin, urea and lymphocyte levels. Although T-SPOT.TB test positivity was higher in patients with a previous TB finding in a PA chest X-ray, there was no statistically significant difference (p = 0.093). The applicability of the TST in the diagnosis of latent TB infection in HD patients is difficult and it is likely to give false-negative results. The T-SPOT.TB test is not affected by the BCG vaccine and immunosuppression. Therefore, using the T-SPOT.TB test would be a more appropriate and practical approach in the diagnosis of latent TB in HD patients. Full article

Latent tuberculosis is prevalent in HIV-infected people and has an impact on the progression of AIDS. The aim of this study is to match a more accurate IGRA method for the better detection of latent tuberculosis infection in HIV patients. All 2394 patients enrolled were tested using three IGRA methods. The positive rate consistency of pairwise comparison and risk factors were analyzed. Receiver operator characteristic (ROC) curve analysis was applied to evaluate the diagnostic value of T-SPOTTB. The positive rates of the three methods were statistically different (p < 0.001). The CD4⁺ T cell number statistically impacted the QuantiFERON and Wan Tai tests after the analysis with univariate logistic regression, while no statistical difference was observed in T-SPOT.TB. Additionally, there was a better sensitivity and specificity of T-SPOT.TB if the positive cut-off value of ESAT-6 and CFP-10 was 4.5 and 5.5, respectively. This study provides an insight into the IGRA methods and demonstrated that the positive response detected via QuantiFERON declined with decreased CD4⁺ T cells in the HIV-infected population; T-SPOT.TB functions independently of the CD4⁺ T cell level and Wan Tai was affected in some cases. This will be useful in the diagnosis of LTBI in the HIV-infected population, which will be a key step toward TB elimination in China. Full article

The way to monitor tuberculosis (TB) treatment is extremely lacking in clinical practice. The aim of the study is to assess the role of the TBAg/PHA ratio in the treatment monitoring of TB. TB patients were followed up for 6 months and serial T-SPOT.TB (T-SPOT) assays were performed. In patients with successful treatment outcomes, the ESAT-6 sfc, CFP-10 sfc, and TBAg/PHA ratio all showed a decreased trend after the initiation of treatment. Conversely, PHA sfc showed an increased trend after 2 months of treatment. However, these indicators had moderate performance in distinguishing between before and after 6 months of treatment, and the AUC ranged from 0.702 to 0.839. Notably, the TBAg/PHA ratio in patients without risk factors was of important value in differentiation between before and after treatment. The optimal AUC of TBAg/PHA ratio reached up to 0.890. Patients with unsuccessful treatment outcomes showed persistently high levels of TBAg/PHA ratio. The TBAg/PHA ratio in patients after 6 months of treatment showed a certain potential in distinguishing between patients with successful and unsuccessful treatment outcomes. A further calculation of the TBAg/PHA ratio in T-SPOT assay has potential value in the treatment monitoring of TB, but further confirmation is needed. Full article

The use of Mycobacterium bovis bacillus Calmette–Guérin (BCG) as a live vaccine vehicle is a promising approach for HIV-1-specific T-cell induction. In this study, we used recombinant BCG expressing HIVACAT T-cell immunogen (HTI), BCG.HTI^2auxo.int. BALB/c mice immunization with BCG.HTI^2auxo.int prime and MVA.HTI boost was safe and induced HIV-1-specific T-cell responses. Two weeks after boost, T-cell responses were assessed by IFN-γ ELISpot. The highest total magnitude of IFN-γ spot-forming cells (SFC)/10⁶ splenocytes was observed in BCG.HTI^2auxo.int primed mice compared to mice receiving MVA.HTI alone or mice primed with BCGwt, although the differences between the vaccination regimens only reached trends. In order to evaluate the differences in the breadth of the T-cell immune responses, we examined the number of reactive peptide pools per mouse. Interestingly, both BCG.HTI^2auxo.int and BCGwt primed mice recognized an average of four peptide pools per mouse. However, the variation was higher in BCG.HTI^2auxo.int primed mice with one mouse recognizing 11 peptide pools and three mice recognizing few or no peptide pools. The recognition profile appeared to be more spread out for BCG.HTI^2auxo.int primed mice and mice only receiving MVA.HTI. Here, we describe a useful vaccine platform for priming protective responses against HIV-1/TB and other prevalent infectious diseases. Full article

Ten million cases of tuberculosis (TB) were reported in 2018 with a further 1.5 million deaths attributed to the disease. Improved vaccination strategies are urgently required to tackle the ongoing global TB epidemic. In the absence of a validated correlate of protection, highly characterised pre-clinical models are required to assess the protective efficacy of new vaccination strategies. In this study, we demonstrate the application of a rhesus macaque ultra-low dose (ULD) aerosol M. tuberculosis challenge model for the evaluation of TB vaccination strategies by directly comparing the immunogenicity and efficacy of intradermal (ID) and aerosol BCG vaccination delivered using a portable vibrating mesh nebulizer (VMN). Aerosol- and ID-delivered Bacille Calmette-Guérin (BCG) induced comparable frequencies of IFN-γ spot forming units (SFU) measured in peripheral blood mononuclear cells (PBMCs) by ELISpot, although the induction of IFN-γ SFU was significantly delayed following aerosol immunisation. This delayed response was also apparent in an array of secreted pro-inflammatory and chemokine markers, as well as in the frequency of antigen-specific cytokine producing CD4 and CD8 T-cells measured by multi-parameter flow cytometry. Interrogation of antigen-specific memory T-cell phenotypes revealed that vaccination-induced CD4 and CD8 T-cell populations primarily occupied the central memory (TCM) and transitional effector memory (TransEM) phenotype, and that the frequency of CD8 TCM and TransEM populations was significantly higher in aerosol BCG-vaccinated animals in the week prior to M. tuberculosis infection. The total and lung pathology measured following M. tuberculosis challenge was significantly lower in vaccinated animals relative to the unvaccinated control group and pathology measured in extra-pulmonary tissues was significantly reduced in aerosol BCG-vaccinated animals, relative to the ID-immunised group. Similarly, significantly fewer viable M. tuberculosis CFU were recovered from the extra-pulmonary tissues of aerosol BCG-vaccinated macaques relative to unvaccinated animals. In this study, a rhesus macaque ULD M. tuberculosis aerosol challenge model was applied as a refined and sensitive system for the evaluation of TB vaccine efficacy and to confirm that aerosol BCG vaccination delivered by portable VMN can confer a significant level of protection that is equivalent, and by some measures superior, to intradermal BCG vaccination. Full article

Background: Given the lack of a gold standard for latent tuberculosis infection (LTBI) and paucity of performance data from endemic settings, we compared test performance of the tuberculin skin test (TST) and two interferon-gamma-release assays (IGRAs) among health-care workers (HCWs) using latent class analysis. The study was conducted in Cape Town, South Africa, a tuberculosis and human immunodeficiency virus (HIV) endemic setting Methods: 505 HCWs were screened for LTBI using TST, QuantiFERON-gold-in-tube (QFT-GIT) and T-SPOT.TB. A latent class model utilizing prior information on test characteristics was used to estimate test performance. Results: LTBI prevalence (95% credible interval) was 81% (71–88%). TST (10 mm cut-point) had highest sensitivity (93% (90–96%)) but lowest specificity (57%, (43–71%)). QFT-GIT sensitivity was 80% (74–91%) and specificity 96% (94–98%), and for TSPOT.TB, 74% (67–84%) and 96% (89–99%) respectively. Positive predictive values were high for IGRAs (90%) and TST (99%). All tests displayed low negative predictive values (range 47–66%). A composite rule using both TST and QFT-GIT greatly improved negative predictive value to 90% (range 80–97%). Conclusion: In an endemic setting a positive TST or IGRA was highly predictive of LTBI, while a combination of TST and IGRA had high rule-out value. These data inform the utility of LTBI-related immunodiagnostic tests in TB and HIV endemic settings. Full article

Background and objective: Lithuania belongs to the group of countries with a high-incidence of tuberculosis (TB). Some scientific studies show that the interferon-gamma release assay is more accurate and correlates more highly with TB exposure as compared to the tuberculin skin test (TST). This study aimed at comparing the efficacy between the T SPOT TB and TST for diagnosing TB among Lithuanian adults.
Materials and methods: Individuals with diagnosed TB, healthcare workers with known risk for TB and individuals without any known risk for TB underwent clinical examinations, interviews about their history of TB exposure and chest radiography. Then the TST and the T SPOT TB were performed on patients.
Results: A positive T SPOT TB was more common in the group with diagnosed TB compared to healthcare workers and the low risk for TB groups (97.5%, 36.4%, and 0%, respectively, P < 0.01). Positive TST results did not differ between the groups with diagnosed TB and the healthcare workers (92.5% vs. 95.5%, P > 0.05). Agreement between TST and T SPOT TB was poor (kappa 0.14, P > 0.05). T SPOT TB had higher specificity and sensitivity compared to TST (area under the ROC 0.9 ± 0.04, P < 0.01, vs. 0.5 ± 0.06, P > 0.05).
Conclusions: The T SPOT TB showed greater accuracy in diagnosing TB than TST did. Positive T SPOT TB result but not the TST was more common in patients with diagnosed TB. Full article

Introduction: This study is a part of the project on interferon gamma release assays performed in the group of untreated sarcoidosis patients formerly BCG vaccinated. The aim of the study was to assess the rate of positive commercial interferon γ release assays in sarcoidosis patients. We discussed the results in the context of hypothesis that M. tuberculosis antigens may play a role in the pathogenesis of sarcoidosis. Material and Methods: 151 patients, mean age 38 ± 10.3, treatment naive, with newly diagnosed pulmonary sarcoidosis were enrolled into the study. All participants underwent QFT-GIT assay. A subgroup of 81 patients underwent also T-SPOT.TB assay. Results: QFT-GIT was positive in 7/151. T-SPOT.TB was positive in 3/81. There were no indeterminate results in both IGRAs. There was no statistically significant relationship between IGRAs results and sarcoidosis parameters such as the radiologic stage, disease duration and the presence of Löfgren’s syndrome. Conclusions: In sarcoidosis patients formerly BCG vaccinated, positive rate of IGRAs was 4.6% for QFT-GIT and 3.7% for T-SPOT.TB. We did not find the influence of the selected parameters of sarcoidosis on IGRAs results. Full article

Tuberculosis is a global health problem. The Mycobacterium bovis Bacille Calmette Guerin (BCG) vaccine has variable efficacy (0–80%) so there is a drive to develop novel vaccines. The cytokine, interferon gamma (IFNγ), is an essential component of the protective response to M. tuberculosis (M. tb) infection and is also produced in response to BCG vaccination. Induction of an IFNγ response is used as a biomarker of successful vaccination in the assessment of new tuberculosis (TB) vaccines. The IFNγ ELISPOT assay provides an important tool for TB research. It is used for both the diagnosis of infection (T.Spot assay), and for the evaluation of the immunogenicity of new TB vaccine candidates in human clinical trials, in the non-human primate (NHP) model of TB infection studies. The ELISPOT assay captures IFNγ produced by peripheral blood mononuclear cells (PBMCs) following specific stimulation, onto a membrane so individual cells can be enumerated and the frequency of responding cells determined. Hence spot forming units (SFU) per 10⁶ cells provide the traditional measure for ELISPOT assays. The discriminatory power of SFU is limited. In some situations, the number of SFU in BCG vaccinated, and unvaccinated, subjects was found to be similar, although the spots were observed to be larger in vaccinated subjects. Spot size potentially provides a measure of the quantity of cytokine produced by individual cells. The AID ELISPOT plate reader software used to determine frequency of spots also has the capability to determine the size of each spot. Consideration of spot size in combination with spot forming units was investigated in our studies of BCG immunogenicity. This additional readout was found to enhance the discriminatory power of the ELISPOT assay, and provide more information on the immune response to BCG vaccination and infection with M.tb. Full article

Introduction: Diagnostics of latent tuberculosis infection (LTBI) has been based on a century-old tuberculin skin test (TST). However, a positive reaction can result not only from infection with Mycobacterium tuberculosis, but also from BCG vaccination or cross-reaction with nontuberculous mycobacteria. T-SPOT.TB assay is a new test to diagnose tuberculosis infection by measuring in vitro T-cell interferon-gamma release in response to two Mycobacterium tuberculosis-specific antigens: ESAT-6 and CFP-10. Material and methods: T-SPOT.TB assay was performed on samples of whole blood (n = 137) from March to September 2010. Tuberculin skin test was carried out in 96 participants. A positive TST result was considered to be an induration of 10 mm or more. Results: Of the 137 patients tested, T-SPOT.TB assay results were positive in 37 (27%), negative in 98 (71.5%) and indeterminate in only 2 (1.5%) persons. We analyzed T-SPOT.TB and TST results in 96 patients who were subjected to both tests. Concordance between T-SPOT.TB and TST results (a 10-mm skin reaction interpreted as positive) was 79%. Fifteen (15.6%) patients had a positive TST result and a negative T-SPOT.TB, and 5 (5.2%) patients had a negative TST result and a positive T-SPOT.TB. We observed a good correlation between positive T-SPOT.TB results and the diameter of induration of ≥15 mm in TST results. Conclusions: T-SPOT.TB offers a more accurate approach than TST in the identification of tuberculosis infection. The study showed that the test T-SPOT.TB is a good diagnostic tool in identifying persons with tuberculosis infection. For a full confirmation of this assessment, it is necessary to examine more cases. Full article

Dotychczas jednym z ważnych narzędzi diagnostycznych zakażenia prątkiem gruźlicy był skórny odczyn tuberkulinowy—jest on jednak mało swoisty i mało czuły. W niniejszym artykule omówiono nowe testy w diagnostyce utajonej infekcji gruźliczej oraz czynnej postaci choroby. Zasada ich działania opiera się na pomiarze interferonu gamma (IFN-γ) wydzielanego przez limfocyty T po stymulacji przez antygeny swoiste dla prątka gruźlicy: ESAT-6, CFP-10. Omówiono czułość i swoistość testów QuantiFERON-TB Gold oraz T-SPOT.TB zarówno w zakażeniu, jak i w czynnej postaci choroby, porównanie ich z tuberkulinowym testem skórnym oraz problem niezgodności wyników otrzymanych za pomocą tych testów. Full article

Tuberculosis is one of the biggest global health problems. One-third of the world’s population (2 billion) is latently infected with tuberculosis. The tuberculin skin test is commonly used to diagnose tuberculosis infection. This test has poor specificity and sensitivity, cross-reactivity with bacille Calmette-Guérin vaccination and many environmental mycobacteria, and poor sensitivity (only 75–90% in active tuberculosis). Mycobacterium tuberculosis activates a strong T cell-mediated immune response. That is why, a better marker for tuberculosis infection could be the presence of mycobacteria specific interferon-y-secreting T cells. These cells can be identified in blood or any other sample, which contains T cells. The test specificity is 99.9% (in low-risk control groups), and the sensitivity is 97.2% (in subjects with culture-confirmed active disease). New in vitro diagnostic test of tuberculosis, based on tuberculosis-induced immunological mechanisms, seems to be more specific and useful as previous methods. Full article