Private sector tuberculosis prevention in the US: Characteristics associated with interferon-gamma release assay or tuberculin skin testing.
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SUBMITTER: Stockbridge EL
PROVIDER: S-EPMC5873986 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background Diabetes mellitus (DM) patients with latent tuberculosis infection (LTBI) have an increased risk of developing active tuberculosis (TB) due to impaired immunity. The performance of currently available immune response-based assays for identification of TB infection had been rarely evaluated in patients with type 2 DM (T2DM) in China. Methods A prospective study was conducted to investigate the status of LTBI in patients with confirmed T2DM. At the baseline survey, the prevalence of LTBI was tested using interferon-gamma release assay (IGRA), tuberculin skin test (TST) and creation tuberculin skin test (C-TST) in parallel. After a 3-month interval, the participants were retested by the three assays to estimate their performance in the serial testing. Results A total of 404 participants with T2DM were included in the study. At baseline, after excluding active TB, the prevalence of LTBI identified by TST (≥ 10 mm), C-TST (≥ 5 mm) and IGRA (≥ 0.35 IU/ml) were 9.65% (39/404), 10.40% (42/404) and 14.85% (60/404), respectively. The concordance of TST and C-TST results with IGRA results was 86.39% (349/404) and 92.08% (372/404) with a Kappa coefficient of 0.37 [95% confidence interval (CI): 0.24– 0.50] and 0.64 (95% CI: 0.53– 0.76), respectively. After a 3-month interval, the continuous results of TST, C-TST and IGRA were observed to be increased with testing conversion for 50, 26 and 27 patients, respectively. For TST and C-TST conversions, the distribution of their quantitative results in serial tests varied significantly when further classified by baseline IGRA dichotomous results. Conclusion In studied patients with T2DM, C-TST showed higher consistency with IGRA as compared to TST. The present of conversion observed in serial testing suggested that boosting effect of skin testing should be considered for identify of LTBI in patients with T2DM.
| S-EPMC9754324 | biostudies-literature
Project description:National guidelines recommend screening for latent tuberculosis infection (LTBI) in all HIV-infected patients. Thus, the objective of this study was to measure protocol adherence to national guidelines regarding LTBI screening for HIV-infected patients entering care at an urban primary care clinic specializing in HIV care, identify clinical and other characteristics associated with adherence, and determine whether transitioning from the tuberculin skin test (TST) to the interferon-gamma release assay (IGRA) improved adherence. We conducted a retrospective study using protocol adherence to LTBI screening guidelines within twelve months of entering care at an HIV clinic as the primary outcome. Successful protocol adherence was defined as the placement and reading of a TST, performance of an IGRA, or a note in study clinic records documenting prior testing or treatment for tuberculosis in an outside setting. Multivariable modified Poisson regression models were used in analyses. Overall, 32% (n?=?118/372) of patients received LTBI screening within twelve months of entering care. Protocol adherence to LTBI screening guidelines increased from 28% to 37% following the transition from TST to IGRA screening. IGRA screening [adjusted prevalence ratio: 1.45, 95% confidence limits: (1.07, 1.96)], male sex [1.47 (1.05, 2.07)], transfer patient status [1.51 (1.05, 2.18)], and greater than one year of clinic attendance [1.62 (1.06, 2.48)] were independently associated with protocol adherence. Among patients without prior LTBI screening or treatment, patients entering the clinic in 2013 under the IGRA screening protocol were more likely to be screened for LTBI compared to patients entering under the TST screening protocol (34.3% vs. 9.7%, p?<?0.001). In conclusion, transitioning from TST to IGRA-based screening improved adherence to screening guidelines. However, further work on improving adherence to LTBI screening guidelines among HIV-infected patients is needed.
| S-EPMC5735423 | biostudies-literature
Project description:ImportanceElimination of tuberculosis (TB) disease in the US hinges on the ability of tests to detect individual risk of developing disease to inform prevention. The relative performance of 3 available TB tests-the tuberculin skin test (TST) and 2 interferon-γ release assays (IGRAs; QuantiFERON-TB Gold In-Tube [QFT-GIT] and SPOT.TB [TSPOT])-in predicting TB disease development in the US remains unknown.ObjectiveTo compare the performance of the TST with the QFT-GIT and TSPOT IGRAs in predicting TB disease in high-risk populations.Design, setting, and participantsThis prospective diagnostic study included participants at high risk of TB infection (TBI) or progression to TB disease at 10 US sites between 2012 and 2020. Participants of any age who had close contact with a case patient with infectious TB, were born in a country with medium or high TB incidence, had traveled recently to a high-incidence country, were living with HIV infection, or were from a population with a high local prevalence were enrolled from July 12, 2012, through May 5, 2017. Participants were assessed for 2 years after enrollment and through registry matches until the study end date (November 15, 2020). Data analysis was performed in June 2023.ExposuresAt enrollment, participants were concurrently tested with 2 IGRAs (QFT-GIT from Qiagen and TSPOT from Oxford Immunotec) and the TST. Participants were classified as case patients with incident TB disease when diagnosed more than 30 days from enrollment.Main outcomes and measuresEstimated positive predictive value (PPV) ratios from generalized estimating equation models were used to compare test performance in predicting incident TB. Incremental changes in PPV were estimated to determine whether predictive performance significantly improved with the addition of a second test. Case patients with prevalent TB were examined in sensitivity analysis.ResultsA total of 22 020 eligible participants were included in this study. Their median age was 32 (range, 0-102) years, more than half (51.2%) were male, and the median follow-up was 6.4 (range, 0.2-8.3) years. Most participants (82.0%) were born outside the US, and 9.6% were close contacts. Tuberculosis disease was identified in 129 case patients (0.6%): 42 (0.2%) had incident TB and 87 (0.4%) had prevalent TB. The TSPOT and QFT-GIT assays performed significantly better than the TST (PPV ratio, 1.65 [95% CI, 1.35-2.02] and 1.47 [95% CI, 1.22-1.77], respectively). The incremental gain in PPV, given a positive TST result, was statistically significant for positive QFT-GIT and TSPOT results (1.64 [95% CI, 1.40-1.93] and 1.94 [95% CI, 1.65-2.27], respectively).Conclusions and relevanceIn this diagnostic study assessing predictive value, IGRAs demonstrated superior performance for predicting incident TB compared with the TST. Interferon-γ release assays provided a statistically significant incremental improvement in PPV when a positive TST result was known. These findings suggest that IGRA performance may enhance decisions to treat TBI and prevent TB.
| S-EPMC10993073 | biostudies-literature
Project description:Health care workers (HCW's) are always at an increased risk of contracting tuberculosis (TB) infection. In Saudi Arabia, Interferon Gamma Release Assay (IGRA) has not been evaluated as a screening tool for latent TB infection (LTBI) among HCW's considering their high demographic diversity. During February 2012 to January 2015 a cross sectional study has been conducted in a tertiary care center with maximum demographically diverse staff population in the capital city-Riyadh. After a short interview and consenting, all the candidates were subjected to tuberculin skin test (TST) and QuantiFERON TB gold In-tube test (QFT). A logistic regression analysis was carried out for establishing the associations between putative risk factors and the diagnostic tests. The candidates were classified according to geographical origin and a detailed analysis was conducted on the impact of their origin towards the results of TST and QFT. Of the 1595 candidates enrolled, 90.6% were BCG vaccinated, female (67.9%) and mainly nurses (53.2%). Candidates with high risk of suspected or confirmed TB patient exposure were 56.1% and 76.5% of them had <10 year's work experience. TST positivity was observed in 503 (31.5%) candidates, while QFT was positive among 399 (25%). Majority of the candidates were non-Saudi (83%) and predominantly (52.4%) from Western Pacific region. Concordant results were obtained in 14.2% of positive cases and 57.7% negative cases. The disagreements between the two tests were relatively high (kappa co-efficient-0.312±0.026, p value- <0.00001) as TST positive/QFT negative discordance was 54.8% while TST negative/QFT positive discordance was 15.7%. Age of the candidates, BCG vaccination, and South East Asian origin were associated with TST positivity while Occupational TB exposure and geographical origin of the candidates were associated with QFT positivity. A regular follow up on recently TST converted candidates showed no progression to active TB. The putative factors associated with the discordance were origin of the candidate (p value <0.001), profession (p value-0.001), BCG vaccination (p value-0.001) and occupational TB exposure level (P value-0.001). The study demonstrated high level prevalence of LTBI among the demographically diverse study candidates. The agreement between QFT and TST was poor, thus QFT alone cannot be recommended in our setting for a routine LTBI screening. Origin of the candidates has strong association with the results of TST and QFT. The discordant results particularly TST negative and QFT positive needs more detailed analysis.
| S-EPMC4858200 | biostudies-literature
Project description:After extensive exposure to Mycobacterium tuberculosis (Mtb), most individuals acquire latent Mtb infection (LTBI) defined by a positive tuberculin skin test (TST) or interferon-γ release assay (IGRA). To identify mechanisms of resistance to Mtb infection, we compared transcriptional profiles from highly exposed contacts who resist TST/IGRA conversion (resisters, RSTRs) and controls with LTBI using RNAseq. Gene sets related to carbon metabolism and free fatty acid (FFA) transcriptional responses enriched across 2 independent cohorts suggesting RSTR and LTBI monocytes have distinct activation states. We compared intracellular Mtb replication in macrophages treated with FFAs and found that palmitic acid (PA), but not oleic acid (OA), enhanced Mtb intracellular growth. This PA activity correlated with its inhibition of proinflammatory cytokines in Mtb-infected cells. Mtb growth restriction in PA-treated macrophages was restored by activation of AMP kinase (AMPK), a central host metabolic regulator known to be inhibited by PA. Finally, we genotyped AMPK variants and found 7 SNPs in PRKAG2, which encodes the AMPK-γ subunit, that strongly associated with RSTR status. Taken together, RSTR and LTBI phenotypes are distinguished by FFA transcriptional programs and by genetic variation in a central metabolic regulator, which suggests immunometabolic pathways regulate TST/IGRA conversion.
| S-EPMC8279582 | biostudies-literature
Project description:Treatment of latent Mycobacterium tuberculosis infection on the basis of the tuberculin skin test (TST) result is inaccurate due to the false-positive TST results that occur after Mycobacterium bovis BCG vaccination or exposure to nontuberculous mycobacteria (NTM). Gamma interferon release assays (IGRAs) are based on M. tuberculosis-specific antigens. In a previous study among BCG-naïve military employees, a positive TST result after deployment was mostly associated with a negative IGRA result, suggesting exposure to NTM. Data regarding the kinetics of IGRAs are limited and controversial. The present study aimed to reassess the rate of false-positive TST results and to evaluate the kinetics of the Quantiferon TB Gold In-Tube assay (QFT-Git) in military personnel with a positive TST result. QFT-Git was performed at the time of inclusion in the study and was repeated after 2, 6, 12, and 18 or 24 months. Of 192 participants, 17 were recruits and 175 were screened after deployment (n = 169) or because of travel or health care work. Baseline positive QFT-Git results were observed in 7/17 (41.2%) and 12/174 (6.9%) participants, respectively. During follow-up, a negative QFT-Git result remained negative in 163/165 (98.8%) participants. Of 18 subjects with an initial positive QFT-Git result, reversion to a negative result occurred in 1/6 (16%) recruits, whereas it occurred in 8/12 (66%) subjects after deployment or with other risk factors (P = 0.046). The quantitative result was significantly lower in subjects with reversion than in those with consistent positive results (P = 0.017). This study confirmed a low rate of positive QFT-Git results among military personnel with a positive TST result after deployment, supporting the hypothesis of exposure to NTM. Reversion of the majority of initially low-positive QFT-Git results indicates that QFT-Git may be useful for the diagnosis of later reinfections.
| S-EPMC2884429 | biostudies-literature
Project description:BACKGROUND/AIMS:Latent tuberculosis screening is mandatory prior to initiating anti-tumor necrosis factor (anti-TNF) medications. Guidelines recommend interferon-gamma release assays (IGRA) as first line screening method for the general population. Studies provided conflicting evidence on IGRA and tuberculin skin test (TST) performance in inflammatory bowel disease (IBD) patients. We assessed test concordance and the effects of immunosuppression on their performance in IBD patients. METHODS:We searched MEDLINE, Embase and Cochrane databases (2011-2018) for studies testing TST and IGRA in IBD. Primary outcome was TST and IGRA concordance. Secondary outcomes were effects of immunosuppressive therapy on performance. Immunosuppression defined as either steroids, thiopurine, methotrexate or cyclosporine use. We used the pooled random effects model to adjust for heterogeneity analyzed using (I2-Q statistics). We compared the fixed model to exclude smaller study effects. RESULTS:Sixteen studies (2,488 patients) were included. Pooled TST and IGRA concordance was 85% (95% confidence interval [CI], 81%-88%; P=0.01). Effects of immunosuppression were reported in 8 studies (814 patients). The odds ratio of testing positive by IGRA decreased to 0.57 if immunosuppressed (95% CI, 0.31-1.03; P=0.06). The odds ratio of testing positive by TST if immunosuppressed was 1.14 (95% CI, 0.61-2.12; P=0.69). The fixed model yielded similar results, however the negative effect of immunosuppression on IGRA reached statistical significance (P=0.01). CONCLUSIONS:While concordance was 85% between TST and IGRA, the performance of IGRA seems to be negatively affected by immunosuppression. Given the importance of detecting latent tuberculosis prior to anti-TNF initiation, further randomized controlled trials comparing the performance of TST and IGRA in IBD patients are needed.
| S-EPMC7385575 | biostudies-literature
Project description:Heavy exposure to Mycobacterium tuberculosis, the etiologic agent of tuberculosis (TB) and among the top infectious killers worldwide, results in infection that is cleared, contained, or progresses to disease. Some heavily exposed tuberculosis contacts show no evidence of infection using the tuberculin skin test (TST) and interferon gamma release assay (IGRA); yet the mechanisms underlying this "resister" (RSTR) phenotype are unclear. To identify transcriptional responses that distinguish RSTR monocytes, we performed transcriptome sequencing (RNA-seq) on monocytes isolated from heavily exposed household contacts in Uganda and gold miners in South Africa after ex vivo M. tuberculosis infection. Gene set enrichment analysis (GSEA) revealed several gene pathways that were consistently enriched in response to M. tuberculosis among RSTR subjects compared to controls with positive TST/IGRA testing (latent TB infection [LTBI]) across Uganda and South Africa. The most significantly enriched gene set in which expression was increased in RSTR relative to LTBI M. tuberculosis-infected monocytes was the tumor necrosis factor alpha (TNF-α) signaling pathway whose core enrichment (leading edge) substantially overlapped across RSTR populations. These leading-edge genes included candidate resistance genes (ABCA1 and DUSP2) with significantly increased expression among Uganda RSTRs (false-discovery rate [FDR], <0.1). The distinct monocyte transcriptional response to M. tuberculosis among RSTR subjects, including increased expression of the TNF signaling pathway, highlights genes and inflammatory pathways that may mediate resistance to TST/IGRA conversion and provides therapeutic targets to enhance host restriction of M. tuberculosis intracellular infection. IMPORTANCE After heavy M. tuberculosis exposure, the events that determine why some individuals resist TST/IGRA conversion are poorly defined. Enrichment of the TNF signaling gene set among RSTR monocytes from multiple distinct cohorts suggests an important role for the monocyte TNF response in determining this alternative immune outcome. These TNF responses to M. tuberculosis among RSTRs may contribute to antimicrobial programs that result in early clearance or the priming of alternative (gamma interferon-independent) cellular responses.
| S-EPMC9241521 | biostudies-literature
Project description:Interferon-gamma (IFN-?) release assays (IGRAs) such as the Quantiferon Gold In-tube test are in vitro assays that measure IFN-? release from T cells in response to M. tuberculosis (Mtb)-specific antigens. Unlike the tuberculin skin test (TST), IGRA is specific and able to distinguish Mtb-infection from BCG vaccination. In this study we evaluated the concordance between TST and IGRA and the efficacy of IGRA in diagnosing new Mtb infection in household contacts (HHC) of pulmonary tuberculosis (PTB) cases. A total of 357 HHC of TB cases in Vitória, Brazil were studied. A TST was performed within 2 weeks following enrollment of the HHC and if negative a second TST was performed at 8-12 weeks. HHC were categorized as initially TST positive (TST+), persistently TST negative (TST-), or TST converters (TSTc), the latter representative of new infection. IGRA was performed at 8-12 weeks following enrollment and the test results were positive in 82% of TST+, 48% of TSTc, and 12% of TST-, indicating poor concordance between the two test results among HHC in each category. Evaluating CXCL10 levels in a subset of IGRA supernatants or lowering the IGRA cutoff value to define a positive test increased agreement between TST and IGRA test results. However, ROC curves demonstrated that this resulted in a trade-off between sensitivity and specificity of IGRA with respect to TST. Together, the findings suggest that until the basis for the discordance between TST and IGRA is fully understood, it may be necessary to utilize both tests to diagnose new Mtb infection in recently exposed HHC. Operationally, in IGRA negative HHC, it may be useful to employ a lower cutoff value for IGRA to allow closer monitoring for potential conversion.
| S-EPMC4018294 | biostudies-literature
Project description:OBJECTIVE:To determine the annual rate of tuberculosis development after a positive tuberculin skin test (TST) or interferon-gamma release assay result (IGRA), or both, among untreated populations with characteristics believed to increase the risk of tuberculosis (at risk populations). DESIGN:Systematic review and meta-analysis. DATA SOURCES:Embase, Medline, and Cochrane Controlled Register of Trials from 1 January 1990 to 17 May 2019, for studies in humans published in English or French. Reference lists were reviewed. ELIGIBILITY CRITERIA AND DATA ANALYSIS:Retrospective or prospective cohorts and randomised trials that included at least 10 untreated participants who tested positive to tuberculosis antigens (contained in TST or IGRA, or both) followed for at least 12 months. Following the preferred reporting items for systematic reviews and meta-analyses (PRISMA) and meta-analyses of observational studies in epidemiology (MOOSE) guidelines, two reviewers independently extracted study data and assessed quality using a modified quality assessment of diagnostic accuracy studies (QUADAS-2) tool. Data were pooled using random effects generalised linear mixed models. MAIN OUTCOME MEASURES:The primary outcome was tuberculosis incidence per 1000 person years among untreated participants who tested positive (TST or IGRA, or both) in different at risk subgroups. Secondary outcomes were the cumulative incidence of tuberculosis and incidence rate ratios among participants with a positive test result for latent tuberculosis infection compared with those with a negative test result in at risk subgroups. RESULTS:122 of 5166 identified studies were included. In three general population studies, the incidence of tuberculosis among 33?811 participants with a TST induration of ?10 mm was 0.3 (95% confidence interval 0.1 to 1.1) per 1000 person years. Among 116?197 positive test results for latent tuberculosis infection in 19 different at risk populations, incidence rates were consistently higher than those in the general population. Among all types of tuberculosis contacts, the incidence of tuberculosis was 17.0 (95% confidence interval 12.9 to 22.4) per 1000 person years for participants with a positive IGRA result and 8.4 (5.6 to 12.6) per 1000 person years for participants with a positive TST result of ?5 mm. Among people living with HIV, the incidence of tuberculosis was 16.9 (10.5 to 27.3) for participants with a positive IGRA result and 27.1 (15.0 to 49.0) for participants with a positive TST result of ?5 mm. Rates were also high for immigrants, people with silicosis or requiring dialysis, transplant recipients, and prisoners. Incidence rate ratios among test positive versus test negative participants were significantly greater than 1.0 in almost all risk groups, for all tests. CONCLUSIONS:The incidence of tuberculosis is substantial in numerous at risk populations after a positive TST or IGRA result. The information from this review should help inform clinical decisions to test and treat for latent tuberculosis infection. STUDY REGISTRATION:PROSPERO CRD42019136608.
| S-EPMC7190060 | biostudies-literature