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1.  Comparison of an ESAT-6/CFP-10 Peptide-Based Enzyme-Linked Immunospot Assay to a Tuberculin Skin Test for Screening of a Population at Moderate Risk of Contracting Tuberculosis▿  
Screening for latent tuberculosis infection (LTBI) with the Mantoux tuberculin skin test (TST) has many limitations including false-positive results due to Mycobacterium bovis bacillus Calmette-Guérin (BCG) vaccination. Three hundred ninety adult inmates with normal screening chest radiographs in a county jail were evaluated for LTBI using TST and an ESAT-6/CFP-10 peptide-based enzyme-linked immunospot assay (T-SPOT.TB). LTBI prevalence rates were 19.0% and 8.5% by T-SPOT.TB and TST, respectively. Overall agreement between test results was 82.8% (κ = 0.29). Positive T-SPOT.TB results were significantly associated with increased age (odds ratio [OR], 1.04; 95% confidence interval [CI], 1.01 to 1.06) and intravenous drug use history (OR, 2.92; 95% CI, 1.36 to 6.27). Positive TST results were significantly associated with increased age (OR, 1.06; 95% CI, 1.02 to 1.09) and foreign birth (OR, 6.61; 95% CI, 1.98 to 22.01). Discordant covariates between the assay results included increased age (OR, 0.96; 95% CI, 0.94 to 0.99) and intravenous drug use history (OR, 0.41; 95% CI, 0.19 to 0.88). T-SPOT.TB reactivity is unaffected by prior BCG vaccination. T-SPOT.TB may be more sensitive than TST in diagnosing LTBI among a moderate risk population of inmates, particularly those with intravenous drug use history. Longitudinal studies are needed to assess the positive predictive value of T-SPOT.TB in identifying those most likely to convert to active disease in general populations as well as in high-risk subpopulations.
doi:10.1128/CVI.00073-07
PMCID: PMC1951077  PMID: 17442844
2.  Comparison of Two Commercially Available Gamma Interferon Blood Tests for Immunodiagnosis of Tuberculosis▿  
We evaluated the T-SPOT.TB and Quantiferon-TB Gold In tube (QFN-G-IT) tests for diagnosing Mycobacterium tuberculosis infection. T-SPOT.TB was more sensitive than QFN-G-IT in diagnosing both active and latent infection. Both gamma interferon tests were unaffected by prior Mycobacterium bovis BCG vaccination. Among children who were not BCG vaccinated but had a positive tuberculin skin test, QFN-G-IT was negative in 53.3% of cases, and T-SPOT.TB was negative in 50% of cases.
doi:10.1128/CVI.00364-07
PMCID: PMC2223867  PMID: 17978008
3.  Comparison of Two Gamma Interferon Release Assays and Tuberculin Skin Testing for Tuberculosis Screening in a Cohort of Patients with Rheumatic Diseases Starting Anti-Tumor Necrosis Factor Therapy ▿ 
Clinical and Vaccine Immunology : CVI  2011;18(12):2102-2108.
Gamma interferon release assays (IGRAs) are increasingly used for latent Mycobacterium tuberculosis infection (LTBI) screening in patients with rheumatic diseases starting anti-tumor necrosis factor (anti-TNF) therapies. We compared the performances of two IGRAs, an enzyme-linked immunospot release assay (T-SPOT.TB) and an enzyme-linked immunosorbent assay (QuantiFERON-TB Gold In Tube [QFT-GIT]), to that of tuberculin skin testing (TST) for LTBI screening of 157 consecutive rheumatic patients starting anti-TNF therapies. Among 155 patients with valid results, 58 (37%) were positive by TST, 39 (25%) by T-SPOT.TB assay, and 32 (21%) by QFT-GIT assay. IGRAs were associated more strongly with at least one risk factor for tuberculosis (TB) than TST. Risk factors for a positive assay included chest X-ray findings of old TB (TST), advanced age (both IGRAs), origin from a country with a high TB prevalence, and a positive TST (T-SPOT.TB assay). Steroid use was negatively associated with a positive QFT-GIT assay. The agreement rate between IGRAs was 81% (kappa rate = 0.47), which was much higher than that observed between an IGRA and TST. If positivity by either TST or an IGRA was required for LTBI diagnosis, then the rate of LTBI would have been 46 to 47%, while if an IGRA was performed only for TST-positive patients, the respective rate would have been 11 to 17%. In conclusion, IGRAs appear to correlate better with TB risk than TST and should be included in TB screening of patients starting anti-TNF therapies. In view of the high risk of TB in these patients, a combination of one IGRA and TST is probably more appropriate for LTBI diagnosis.
doi:10.1128/CVI.05299-11
PMCID: PMC3232699  PMID: 21994356
4.  Evaluation of Interferon-Gamma Release Assays in the Diagnosis of Recent Tuberculosis Infection in Health Care Workers 
PLoS ONE  2009;4(8):e6686.
Background
Health care workers (HCWs) are a group at risk of latent tuberculosis infection (LTBI). The aims of this study were to determine IFN-γ response by QuantiFERON-TB GOLD In Tube (QFN-G-IT) and T-SPOT.TB in HCWs, comparing the results with tuberculin skin test (TST); and to analyze the capacity of IFN-γ tests to detect recent versus remote LTBI with a prolonged stimulation test (PST).
Methodology/Principal Findings
A total of 147 HCWs were enrolled; 23 of whom were BCG vaccinated. 95 HCWs (64.6%) had a previous positive TST and were not retested; and 52 HCWs had a previous negative TST or were tested for the first time. When we analysed individuals without previous positive TST, the number of positive results for T-SPOT.TB was 12/52 (23.1%); and for QFN-G-IT, 9/52 (17.3%). The global concordance (κ) between T-SPOT.TB and QFN-G-IT with TST was 0.754 and 0.929 respectively. Of individuals with previous positive TST, T-SPOT.TB and QFN-G-IT were negative in 51.6% (49/95) and 62.1% (59/95) respectively, decreasing the concordance to 0.321 and 0.288, respectively. In non-BCG vaccinated HCWs with previous positive TST a positive IFN-γ test was associated with degree of exposure and diameter of TST. PST was performed in 24 HCW with previous positive TST and negative IFN-γ tests. PST was developed in 3 cell cultures stimulated with medium alone, ESAT-6 and CFP-10, respectively. In the third and sixth day of incubation period, part of the supernatants were replaced with complete medium supplemented with (rIL)-2. On day 9, ELISPOT assay was performed. In 14 samples PST was not valid due to not having enough cells. In 8 cases, the response was negative, and in 2 cases positive, suggesting that these patients were infected with Mycobacterium tuberculosis in some point in the past.
Conclusions
Both IFN-γ tests showed a similar number of positive results, and concordance between the tests was excellent. None of the tests was affected by prior BCG vaccination. IFN-γ tests are a useful tool for detecting recent infection in HCW population.
doi:10.1371/journal.pone.0006686
PMCID: PMC2726945  PMID: 19701460
5.  Contribution of Interferon gamma release assays testing to the diagnosis of latent tuberculosis infection in HIV-infected patients: A comparison of QuantiFERON-TB Gold In Tube, T-SPOT.TB and tuberculin skin test 
BMC Infectious Diseases  2012;12:169.
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.
doi:10.1186/1471-2334-12-169
PMCID: PMC3482589  PMID: 22849726
6.  Strategy to Better Select HIV-Infected Individuals for Latent TB Treatment in BCG-Vaccinated Population 
PLoS ONE  2013;8(8):e73069.
Objective
To evaluate the T-SPOT.TB interferon-γ releasing assay and the tuberculin skin test (TST), for the diagnosis of latent tuberculosis infection(LTBI) and the development of subsequent active tuberculosis, in BCG-vaccinated HIV-infected individuals.
Methods
HIV-infected individuals without clinical suspicion of active TB or a past history of TB were enrolled from 1 January 2008 to 30 November 2010. Both T-SPOT.TB test and TST were offered to the participants whom were followed up prospectively until April 30, 2012 for development of TB.
Results
Among the 909 participants, 25% had positive TST reactions with cut-off point of 5 mm and 15% had positive T-SPOT.TB results. After a median follow-up of 2.97 years, there were 5 cases developed culture-confirmed active TB (all had dual positive TST and T-SPOT.TB results), and the incidence was 0.17 per 100 person-years. The relative risks (RRs) for subsequent active TB in HIV-infected individuals with positive TST results, positive T-SPOT.TB results and dual positive results compared with the risk for individuals with negative results were 40.6 (95% CI 2.1–767.9), 73.9 (95% CI 3.9–1397.7) and 226.5 (95% CI 12.0–4284), respectively. The number needed to treat to prevent one subsequent TB case among patients with a positive TST, a positive T-SPOT.TB and dual positive results was 35, 22 and 8 respectively.
Conclusions
Adopting positive results of the TST and T-SPOT.TB to screen LTBI among BCG-vaccinated HIV-infected individuals might be feasible. Number needed to treat for isoniazid preventive therapy could be reduced significantly by using dual positive strategy.
doi:10.1371/journal.pone.0073069
PMCID: PMC3754919  PMID: 24015285
7.  Interferon-Gamma Release Assay Performance in Pulmonary and Extrapulmonary Tuberculosis 
PLoS ONE  2012;7(3):e32652.
Background
The diagnosis of tuberculosis remains difficult. This study aimed to assess performance of interferon-gamma release assay (IGRA) in diagnosis of active tuberculosis (ATB) with pulmonary and extrapulmonary involvements, and to determine the diagnostic role of IGRA (T-SPOT.TB) and tuberculin skin test (TST) in BCG-vaccinated population.
Methods and Findings
Two hundred twenty-six ATB suspects were recruited and examined with T-SPOT.TB. Among them, fifty-two and seventy-six subjects were simultaneously tested by TST with 5TU or 1TU of purified protein derivative (PPD). The sensitivity of T-SPOT.TB was 94.7% (71/75), comparable in pulmonary and extrapulmonary disease groups (95.6% vs. 93.3%, P>0.05), while the specificity was 84.10% (90/107) but differed in two groups (69.2% vs. 88.9%, P = 0.02). Compared to T-SPOT.TB, TST with 5TU-PPD showed less sensitivity (92.3% vs. 56.4%) and specificity (84.6% vs. 61.5%) (both P<0.01); the sensitivity of TST with 1TU-PPD was 27.8%, and despite its specificity identical to T-SPOT.TB (both 82.8%) positive predictive value (PPV) was only 33.3%. By combining T-SPOT.TB with TST (1TU), the specificity rose to 95%, but the PPV stayed unchanged.
Conclusions
IGRA could function as a powerful immunodiagnostic test to explore pulmonary and extrapulmonary TB, while TST failed to play a reliable or auxiliary role in identifying TB disease and infection in the BCG-vaccinated population.
doi:10.1371/journal.pone.0032652
PMCID: PMC3302779  PMID: 22427859
8.  IFN-γ response on T-cell based assays in HIV-infected patients for detection of tuberculosis infection 
BMC Infectious Diseases  2010;10:348.
Background
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.
Methods
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.
Results
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.
Conclusions
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.
doi:10.1186/1471-2334-10-348
PMCID: PMC3016378  PMID: 21143955
9.  Evaluation of Gamma Interferon Release Assays Using Mycobacterium tuberculosis Antigens for Diagnosis of Latent and Active Tuberculosis in Mycobacterium bovis BCG-Vaccinated Populations▿  
Clinical and Vaccine Immunology : CVI  2010;17(12):1985-1990.
T-cell-based gamma interferon (IFN-γ) release assays (IGRAs) using Mycobacterium tuberculosis-specific antigens have shown higher sensitivity and specificity than the routine tuberculin skin test (TST). However, the effects of Mycobacterium bovis BCG vaccination and anti-tuberculosis (TB) treatment on dynamic T-cell responses to M. tuberculosis-specific antigens in active TB cases have rarely been investigated in regions where TB is endemic. Eighty-nine patients with active pulmonary TB (ATB) and 57 healthy controls (HC) from China were recruited and tested by sputum smear and culture, TSTs, and IGRAs with M. tuberculosis-specific antigens ESAT-6 and CFP-10 (T-SPOT.TB) as well as purified protein derivative (PPD) stimulation. All 146 participants were screened by the T-SPOT.TB assay at recruitment. T-SPOT.TB-positive rates in ATB and HC groups were 87.6% (78/89) and 21.1% (12/57), respectively. Of 38 ATB patients who were both TST and T-SPOT.TB tested, the positive rates were 73.7% (28/38) and 94.7% (36/38), respectively (P = 0.0215), and those in the HC group were 62.3% (33/53) and 18.9% (10/53), respectively (P < 0.0001). The T-SPOT.TB-positive rates declined during TB treatment and were 94.4% (51/54), 86.4% (19/22), and 61.5% (8/13) for ATB patients receiving 0- to 1-month, 1- to 3-month, and 3- to 6-month anti-TB treatment, respectively. The IGRA is a most promising test for both active TB and latent TB infection (LTBI) diagnosis due to the improvement of its specificity and convenience, especially in the Mycobacterium bovis BCG-vaccinated population. Furthermore, the T-SPOT.TB assay using ESAT-6 and CFP-10 in ATB patients during anti-TB treatment could serve as a potential predictor of therapeutic efficacy.
doi:10.1128/CVI.00294-10
PMCID: PMC3008201  PMID: 20943878
10.  Tuberculin skin test and ELISPOT/T. SPOT.TB in children and adolescents with juvenile idiopathic arthritis 
Background
There are controversies regarding the accuracy of the tuberculin skin test (TST) and methods based on the production of interferon gamma by sensitized T cells for the diagnosis of latent tuberculosis infection (LTBI) in pediatrics and immunosuppressed patients. Our objectives are to study TST and ELISPOT/T. SPOT.TB in the diagnosis of LTBI in children and adolescents with JIA undergoing methotrexate, the correlation between both and the sensitivity and specificity of T. SPOT.TB.
Methods
This is an observational prospective longitudinal study in which children and adolescents with JIA undergoing methotrexate therapy were assessed for clinical and epidemiological data for LTBI, in addition to performing TST and T. SPOT.TB at baseline and after 3 and 12months.
Results
There were 24 patients. The prevalence of LTBI at inclusion was 20.8%, the incidence after initiation of immunosuppressions 26.3% and the prevalence at the end of the study 41.6%. Epidemiological history positive for TB showed a relative risk of 2.0 for the development of LTBI. Only 2 patients had positive T. SPOT.TB but only in one it was useful for detecting early LTBI. T. SPOT.TB presented a sensitivity of 10%, specificity of 92.8%, and low correlation with TST. No patient developed TB disease at a mean follow-up of 47months.
Conclusions
We found a high prevalence of ILTB that doubled with immunosuppression and that epidemiological history was an important relative risk. T. SPOT.TB showed low sensitivity and high specificity, and no superiority over TST. There was low agreement and little influence of immunosuppression on the results of both tests.
doi:10.1186/1546-0096-12-17
PMCID: PMC4046629  PMID: 24904240
11.  Different screening strategies (single or dual) for the diagnosis of suspected latent tuberculosis: a cost effectiveness analysis 
Background
Previous health economic studies recommend either a dual screening strategy [tuberculin skin test (TST) followed by interferon-γ-release assay (IGRA)] or a single one [IGRA only] for latent tuberculosis infection (LTBI), the former largely based on claims that it is more cost-effective. We sought to examine that conclusion through the use of a model that accounts for the additional costs of adverse drug reactions and directly compares two commercially available versions of the IGRA: the Quantiferon-TB-Gold-In-Tube (QFT-GIT) and T-SPOT.TB.
Methods
A LTBI screening model directed at screening contacts was used to perform a cost-effectiveness analysis, from a UK healthcare perspective, taking into account the risk of isoniazid-related hepatotoxicity and post-exposure TB (2 years post contact) using the TST, QFT-GIT and T-SPOT.TB IGRAs.
Results
Examining costs alone, the TST/IGRA dual screening strategies (TST/T-SPOT.TB and TST/QFT-GIT; £162,387 and £157,048 per 1000 contacts, respectively) cost less than their single strategy counterparts (T-SPOT.TB and QFT-GIT; £203,983 and £202,921 per 1000 contacts) which have higher IGRA test costs and greater numbers of persons undergoing LTBI treatment. However, IGRA alone strategies direct healthcare interventions and costs more accurately to those that are truly infected.
Subsequently, less contacts need to be treated to prevent an active case of TB (T-SPOT.TB and QFT-GIT; 61.7 and 69.7 contacts) in IGRA alone strategies. IGRA single strategies also prevent more cases of post-exposure TB. However, this greater effectiveness does not outweigh the lower incremental costs associated with the dual strategies. Consequently, when these costs are combined with effectiveness, the IGRA dual strategies are more cost-effective than their single strategy counterparts. Comparing between the IGRAs, T-SPOT.TB-based strategies (single and dual; £39,712 and £37,206 per active TB case prevented, respectively) were more cost-effective than the QFT-GIT-based strategies (single and dual; £42,051 and £37,699 per active TB case prevented, respectively). Using the TST alone was the least cost-effective (£47,840 per active TB case prevented). Cost effectiveness values were sensitive to changes in LTBI prevalence, IGRA test sensitivities/specificities and IGRA test costs.
Conclusion
A dual strategy is more cost effective than a single strategy but this conclusion is sensitive to screening test assumptions and LTBI prevalence.
doi:10.1186/1471-2466-10-7
PMCID: PMC2837635  PMID: 20170555
12.  Use of interferon gamma-based assay to diagnose tuberculosis infection in health care workers after short term exposure 
Background
We intended to assess the risk for health care workers (HCWs) of acquiring M. tuberculosis infection after exposure to patients with sputum-smear positive pulmonary tuberculosis at three University Hospitals (Ullevål, Akershus, and Haukeland) in Norway.
Methods
We tested 155 exposed health care workers and 48 healthy controls both with a tuberculin skin test (Mantoux) and the T-SPOT.TB test, a recently developed interferon-γ release assays based on the M. tuberculosis-specific ESAT-6 and CFP10 antigens, to investigate if this test might improve infection control measures.
Results
Among the 155 exposed HCWs tested in this study, 27 individuals were defined as newly infected cases by TST after recent exposure, while only 3 of these had a positive T-SPOT.TB test. The number of T-SPOT.TB positives represents 11% of the individuals defined as recently infected by TST after exposure (3/27) and 2% of the total number of exposed people tested (3/155). In addition, 15 individuals had been previously defined as infected by TST before exposure of whom 2 subjects were T-SPOT.TB positive. All individuals detected as T-SPOT.TB positive belonged to the TST positive group (> 15 mm), and the percentage concordance between T-SPOT.TB and TST, including both previously and newly infected subjects, was 12% (5/42). The 48 control participants used in the study were all T-SPOT.TB negative, but 3 of these subjects were TST positive.
Conclusion
Our data indicate that the frequency of latent TB in the total cohort of HCWs is 3%, whereas the rate of transmission of TB to exposed individuals is approximately 2% and occurs through exposure periods of short duration. Thus, the risk of TB transmission to HCWs following TB exposure in a hospital setting in Norway is low, and improved screening approaches will benefit from the application of specific interferon-γ release assays.
doi:10.1186/1471-2334-9-60
PMCID: PMC2690599  PMID: 19432995
13.  High-sensitive and rapid detection of Mycobacterium tuberculosis infection by IFN-γ release assay among HIV-infected individuals in BCG-vaccinated area 
BMC Immunology  2009;10:31.
Background
An accurate test for Mycobacterium tuberculosis infection is urgently needed in immunosuppressed populations. The aim of this study was to investigate the diagnostic power of enzyme-linked immunospot (ELISPOT)-based IFN-γ release assay in detecting active and latent tuberculosis in HIV-infected population in bacillus Calmette-Guerin (BCG)-vaccinated area. A total of 100 HIV-infected individuals including 32 active tuberculosis patients were recruited. An ELISPOT-based IFN-γ release assay, T-SPOT.TB, was used to evaluate the M. tuberculosis ESAT-6 and CFP-10 specific IFN-γ response. Tuberculin skin test (TST) was performed for all recruited subjects.
Results
The subjects were divided into group HIV+ATB (HIV-infected individuals with active tuberculosis, n = 32), group HIV+LTB (HIV-infected individuals with positive results of T-SPOT.TB assay, n = 46) and group HIV only (HIV-infected individuals with negative results of T-SPOT.TB assay and without evidence of tuberculosis infection, n = 22). In group HIV+ATB and HIV+LTB, T-SPOT.TB positive rate in subjects with TST <5 mm were 50% (16/32) and 41.3% (19/46), respectively. Individuals in group HIV+ATB and HIV+LTB with CD4+ T cells <500/μl, T-SPOT.TB showed a higher sensitivity than TST (64.5% vs. 22.6% and 62.2% vs. 29.7%, respectively, both P < 0.0001). In addition, the sensitivity of T-SPOT.TB assay in group HIV+ATB increased to >85% in patients with TB treatment for less than 1 month and CD4+ T cells ≥200/μl, while for patients treated for more than 3 months and CD4+ T cells <200/μl, the sensitivity was decreased to only 33.3%. Furthermore, the results could be generated by T-SPOT.TB assay within 24 hours, which was more rapid than TST with 48–72 hours.
Conclusion
ELISPOT-based IFN-γ release assay is more sensitive and rapid for the diagnosis of TB infection in Chinese HIV-infected individuals with history of BCG vaccination, and could be an effective tool for guiding preventive treatment with isoniazid in latently infected people and for TB control in China.
doi:10.1186/1471-2172-10-31
PMCID: PMC2700818  PMID: 19476627
14.  Tuberculin Skin Testing and Treatment Modulates Interferon-Gamma Release Assay Results for Latent Tuberculosis in Migrants 
PLoS ONE  2014;9(5):e97366.
Background
Identifying latent tuberculosis infection (LTBI) in people migrating from TB endemic regions to low incidence countries is an important control measure. However, no prospective longitudinal comparisons between diagnostic tests used in such migrant populations are available.
Objectives
To compare commercial interferon (IFN)-gamma release assays (IGRAs) and the tuberculin skin test (TST) for diagnosing LTBI in a migrant population, and the influence of antecedent TST and LTBI treatment on IGRA performance.
Materials and Methods
This cohort study, performed from February to September 2012, assessed longitudinal IGRA and TST responses in Nepalese military recruits recently arrived in the UK. Concomitant T-SPOT.TB, QFT-GIT and TST were performed on day 0, with IGRAs repeated 7 and 200 days later, following treatment for LTBI if necessary.
Results
166 Nepalese recruits were prospectively assessed. At entry, 21 individuals were positive by T-SPOT.TB and 8 individuals by QFT-GIT. There was substantial agreement between TST and T-SPOT.TB positives at baseline (71.4% agreement; κ = 0.62; 95% CI:0.44–0.79), but only moderate concordance between positive IGRAs (38.1% agreement; κ = 0.46; 95% CI:0.25–0.67). When reassessed 7 days following TST, numbers of IGRA-positive individuals changed from 8 to 23 for QFT-GIT (p = 0.0074) and from 21 to 23 for T-SPOT.TB (p = 0.87). This resulted in an increase in IGRA concordance to substantial (64.3% agreement; κ = 0.73; 95% CI:0.58-0.88). Thus, in total on day 0 and day 7 after testing, 29 out of 166 participants (17.5%) provided a positive IGRA and of these 13 were TST negative. Two hundred days after the study commenced and three months after treatment for LTBI was completed by those who were given chemoprophylaxis, 23 and 21 participants were positive by T-SPOT.TB or QFT-GIT respectively. When individual responses were examined longitudinally within this population 35% of the day 7 QFT-GIT-positive, and 19% T-SPOT.TB-positive individuals, were negative by IGRA. When the change in the levels of secreted IFN-γ was examined after chemoprophylaxis the median levels were found to have fallen dramatically by 77.3% from a pre-treatment median concentration of IFN-γ 2.73 IU/ml to a post-treatment median concentration IFN-γ 0.62 (p = 0.0002).
Conclusions
This study suggests differences in the capacity of commercially available IGRAs to identify LTBI in the absence of antecedent TST and that IGRAs, in the time periods examined, may not be the optimal tests to determine the success of chemoprophylaxis for LTBI.
doi:10.1371/journal.pone.0097366
PMCID: PMC4016319  PMID: 24816576
15.  Interferon-gamma release assays are a better tuberculosis screening test for hemodialysis patients: A study and review of the literature 
Diagnosing latent tuberculosis (TB) infection (LTBI) in dialysis patients is complicated by poor response to tuberculin skin testing (TST), but the role of interferon-gamma release assays (IGRAs) in the dialysis population remains uncertain. Seventy-nine patients were recruited to compare conventional diagnosis (CD) with the results of two IGRA tests in a dialysis unit. Combining TST, chest x-ray and screening questionnaire results (ie, CD) identified 24 patients as possible LTBI. IGRA testing identified 22 (QuantiFERON Gold IT, Cellestis, USA) and 23 (T-spot.TB, Oxford Immunotec, United Kingdom) LTBI patients. IGRA and CD correlated moderately (κ=0.59). IGRA results correlated with history of TB, TB contact and birth in an endemic country. TST was not helpful in identifying LTBI patients in this population. The tendency for IGRAs to correlate with risk factors for TB, active TB infection and history of TB argues for their superiority over TST in dialysis patients. There was no superiority of one IGRA test over another.
PMCID: PMC3476553  PMID: 23997776
Dialysis; Host; Immunocompromised; Interferon-gamma release assay; Latent tuberculosis infection; Tuberculin skin testing; Tuberculosis
16.  High Incidence of Tuberculosis Infection in Rheumatic Diseases and Impact for Chemoprophylactic Prevention of Tuberculosis Activation during Biologics Therapy 
We conducted a long-term follow-up study in patients with rheumatic diseases who were candidates for biologics treatment to evaluate the effects of biologic agents on the risk of tuberculosis infection and the effect of prophylactic treatment on tuberculosis activation. One hundred one patients with rheumatic diseases who were candidates for biologics treatment were recruited, and 57 healthy subjects were recruited as controls. Tuberculin skin test (TST) and the T-SPOT.TB test were performed for all subjects at baseline. Follow-up testing by the T-SPOT.TB assay was performed every 6 months in patients with rheumatic diseases and at 2 years of recruitment in the healthy controls. In patients with rheumatic diseases and healthy controls, the TST-positive (induration, ≥10 mm) rates were 37.6% (38/101) and 34.0% (18/53), respectively (P > 0.05), while the T-SPOT.TB-positive rates were 46.5% (47/101) and 21.1 (12/57), respectively (P = 0.0019). Fifty-two patients were followed up at month 6 with a T-SPOT.TB-positive rate of 40.4%, and 49 were followed up for ≥12 months with a T-SPOT.TB-positive rate of 36.7%, with no significant difference in the positive rate at different time points including baseline (P > 0.05). Long-term follow-up revealed that conversion to T-SPOT.TB positivity occurred only in the biologics treatment group, with a positive conversion rate of 11.2% (4/38). Most importantly, no latent tuberculosis developed into active tuberculosis during follow-up with T-SPOT.TB screening and preemptive treatment with isoniazid. Biologics treatment appears to increase the risk of tuberculosis infection. However, tuberculosis activation could be prevented by preemptive isoniazid treatment in patients with latent tuberculosis infection while receiving biologics therapy.
doi:10.1128/CVI.00049-13
PMCID: PMC3675964  PMID: 23554465
17.  Poor concordance between interferon-γ release assays and tuberculin skin tests in diagnosis of latent tuberculosis infection among HIV-infected individuals 
Background
A new generation of diagnostic tests, the interferon-γ release assays (IGRAs), have been developed for the detection of latent tuberculosis infection (LTBI). Limited data are available on their use in HIV-infected persons.
Methods
A cross-sectional study was carried out at 2 HIV clinics in Atlanta to assess the utility of two IGRA tests (T-SPOT.TB [TSPOT] and QuantiFERON-TB Gold in Tube [QFT-3G]) compared to the tuberculin skin test (TST).
Results
336 HIV-infected persons were enrolled. Median CD4 count was 335 cells/μl and median HIV viral load was 400 copies/ml. Overall, 27 patients (8.0%) had at least 1 positive diagnostic test for LTBI: 7 (2.1%) had a positive TST; 9 (2.7%) a positive QFT-3G; and 14 (4.2%) a positive TSPOT. Agreement between the 3 diagnostic tests was poor: TST and TSPOT, [κ = 0.16, 95% CI (-0.06, 0.39)], TST and QFT-3G [κ = 0.23, 95% CI (-0.05, 0.51)], QFT-3G and TSPOT [κ = 0.06, 95% CI (-0.1, 0.2)]. An indeterminate test result occurred among 6 (1.8%) of QFT-3G and 47 (14%) of TSPOT tests. In multivariate analysis, patients with a CD4 ≤ 200 cells/μl were significantly more likely to have an indeterminate result [OR = 3.6, 95% CI (1.9, 6.8)].
Conclusion
We found a low prevalence of LTBI and poor concordance between all 3 diagnostic tests. Indeterminate test results were more likely at CD4 counts ≤ 200 cells/μl. Additional studies among HIV-infected populations with a high prevalence of TB are needed to further assess the utility of IGRAs in this patient population.
doi:10.1186/1471-2334-9-15
PMCID: PMC2649136  PMID: 19208218
18.  Systematic review and meta-analysis on the utility of Interferon-gamma release assays for the diagnosis of Mycobacterium tuberculosis infection in children: a 2013 update 
BMC Infectious Diseases  2014;14(Suppl 1):S6.
Background
Previous meta-analyses regarding the performance of interferon-gamma release assays (IGRAs) for tuberculosis diagnosis in children yielded contrasting results, probably due to different inclusion/exclusion criteria.
Methods
We systematically searched PubMed, EMBASE and Cochrane databases and calculated pooled estimates of sensitivities and specificities of QuantiFERON-TB Gold In Tube (QFT-G-IT), T-SPOT.TB, and tuberculin skin test (TST). Several sub-analysis were performed: stratification by background (low income vs. high income countries); including only microbiological confirmed TB cases; including only studies performing a simultaneous three-way comparison of the three tests, and including immunocompromised children.
Results
Overall, 31 studies (6183 children) for QFT-G-IT, 14 studies (2518 children) for T-SPOT.TB and 34 studies (6439 children) for TST were included in the analyses. In high income countries QFT-G-IT sensitivity was 0.79 (95%IC: 0.75-0.82) considering all the studies, 0.78 (95%CI:0.70-0.84) including only studies performing a simultaneous three-way comparison and 0.86 (95%IC 0.81-0.90) considering only microbiologically confirmed studies. In the same analyses T-SPOT.TB sensitivity was 0.67 (95%IC 0.62-0.73); 0.76 (95%CI: 0.68 to 0.83); and 0.79 (95%IC 0.69-0.87), respectively. In low income countries QFT-G-IT pooled sensitivity was significantly lower: 0.57 (95%IC:0.52-0.61), considering all the studies, and 0.66 (95%IC 0.55-0.76) considering only microbiologically confirmed cases; while T-SPOT.TB sensitivity was 0.61 (95%IC 0.57-0.65) overall, but reached 0.80 (95%IC 0.73-0.86) in microbiologically confirmed cases. In microbiologically confirmed cases TST sensitivity was similar: 0.86 (95%IC 0.79-0.91) in high income countries, and 0.74 (95%IC 0.68-0.80) in low income countries. Higher IGRAs specificity with respect to TST was observed in high income countries (97-98% vs. 92%) but not in low income countries (85-93% vs. 90%).
Conclusions
Both IGRAs showed no better performance than TST in low income countries.
doi:10.1186/1471-2334-14-S1-S6
PMCID: PMC4016555  PMID: 24564486
19.  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 
BMC Infectious Diseases  2011;11:319.
Background
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.
Methods
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.
Results
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).
Conclusions
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.
doi:10.1186/1471-2334-11-319
PMCID: PMC3226666  PMID: 22085801
20.  A Three-Way Comparison of Tuberculin Skin Testing, QuantiFERON-TB Gold and T-SPOT.TB in Children 
PLoS ONE  2008;3(7):e2624.
Background
There are limited data comparing the performance of the two commercially available interferon gamma (IFN-γ) release assays (IGRAs) for the diagnosis of tuberculosis (TB) in children. We compared QuantiFERON-TB gold In Tube (QFT-IT), T-SPOT.TB and the tuberculin skin test (TST) in children at risk for latent TB infection or TB disease.
Methods and Findings
The results of both IGRAs were compared with diagnosis assigned by TST-based criteria and assessed in relation to TB contact history. Results from the TST and at least one assay were available for 96 of 100 children. Agreement between QFT-IT and T-SPOT.TB was high (93% agreement, κ = 0.83). QFT-IT and T-SPOT.TB tests were positive in 8 (89%) and 9 (100%) children with suspected active TB disease. There was moderate agreement between TST and either QFT-IT (75%, κ = 0.50) or T-SPOT.TB (75%, κ = 0.51). Among 38 children with TST-defined latent TB infection, QFT-IT gold and T-SPOT.TB assays were positive in 47% and 39% respectively. Three TST-negative children were positive by at least one IGRA. Children with a TB contact were more likely than children without a TB contact to have a positive IGRA (QFT-IT LR 3.9; T-SPOT.TB LR 3.9) and a positive TST (LR 1.4). Multivariate linear regression analysis showed that the magnitude of both TST induration and IGRA IFN-γ responses was significantly influenced by TB contact history, but only the TST was influenced by age.
Conclusions
Although a high level of agreement between the IGRAs was observed, they are commonly discordant with the TST. The correct interpretation of a negative assay in a child with a positive skin test in clinical practice remains challenging and highlights the need for longitudinal studies to determine the negative predictive value of IGRAs.
doi:10.1371/journal.pone.0002624
PMCID: PMC2440545  PMID: 18612425
21.  Correlation between tuberculin skin test and IGRAs with risk factors for the spread of infection in close contacts with sputum smear positive in pulmonary tuberculosis 
BMC Infectious Diseases  2014;14:258.
Background
The aim of the study was to assess the correlation between the tuberculin skin test (TST) and in vitro interferon-gamma released assays (IGRAs) with risk factors for the spread of infection in smear positive pulmonary tuberculosis (TB) contacts.
Methods
We recruited prospective contacts with smear positive pulmonary TB cases. We looked at human immunodeficiency virus (HIV) infection and other conditions of immunosuppression, presence of BCG vaccination and the degree of exposure to the index case. Patients underwent the TST, chest radiography, sputum analysis when necessary, and IGRA assays (QFN-G-IT and T-SPOT.TB). Presence of cough, diagnostic delay (days between first symptoms and TB diagnostic), contact conditions: room size (square meters) and index of overcrowding (square meters per person) were investigated in the index case.
Results
156 contacts (119 adults, 37 children) of 66 TB patients were enrolled, 2.4 (1-14) contacts per TB case. The positivity of the TST did not correlate with the risk factors studied: presence of cough (p = 0.929); delayed diagnosis (p = 0.244); room size (p = 0.462); overcrowding (p = 0.800). Both QFN-G-IT and T-SPOT.TB, showed significant association with cough (p = 0.001, and p = 0.007) and room size (p = 0.020, and p = 0.023), respectively.
Conclusions
Both IGRA associated better than TST with certain host-related risk factors involved in the transmission of disease, such as the presence of cough.
doi:10.1186/1471-2334-14-258
PMCID: PMC4030278  PMID: 24885850
Tuberculosis infection; Tuberculin skin test; Interferon gamma release assays; IGRA; Overcrowding; Diagnostic delay; Cough
22.  Accuracy of Immunodiagnostic Tests for Active Tuberculosis Using Single and Combined Results: A Multicenter TBNET-Study 
PLoS ONE  2008;3(10):e3417.
Background
The clinical application of IFN-γ release assays (IGRAs) has recently improved the diagnosis of latent tuberculosis infection. In a multicenter study of the Tuberculosis Network European Trialsgroup (TBNET) we aimed to ascertain in routine clinical practice the accuracy of a novel assay using selected peptides encoded in the mycobacterial genomic region of difference (RD) 1 for the diagnosis of active tuberculosis in comparison with tuberculin skin test (TST), QuantiFERON-TB GOLD In-Tube (Cellestis Ltd., Carnegie, Australia) and T-SPOT.TB (Oxfordimmunotec, Abingdon, UK).
Principal Findings
425 individuals from 6 different European centres were prospectively enrolled. We found that sensitivity of the novel test, TST, QuantiFERON-TB GOLD In-Tube and T-SPOT.TB was respectively 73.1%, 85.3%, 78.1%, and 85.2%; specificity was respectively 70.6%, 48.0%, 61.9% and 44.3%; positive likelihood ratios were respectively 2.48, 1.64, 2.05, and 1.53; negative likelihood ratios were respectively 0.38, 0.31, 0.35, 0.33. Sensitivity of TST combined with the novel test, QuantiFERON-TB GOLD In-Tube and T-SPOT.TB increased up to 92.4%, 97.7% and 97.1%, respectively. The likelihood ratios of combined negative results of TST with, respectively, the novel test, QuantiFERON-TB GOLD In-Tube and T-SPOT.TB were 0.19, 0.07 and 0.10.
Conclusions
The assay based on RD1 selected peptides has similar accuracy for active tuberculosis compared with TST and commercial IGRAs. Then, independently of the spectrum of antigens used in the assays to elicit mycobacterial specific immune responses, the novel test, IGRAs, and the TST do not allow an accurate identification of active tuberculosis in clinical practice. However, the combined use of the novel assay or commercial IGRAs with TST may allow exclusion of tuberculosis.
doi:10.1371/journal.pone.0003417
PMCID: PMC2561073  PMID: 18923709
23.  Systematic Review: T-Cell–based Assays for the Diagnosis of Latent Tuberculosis Infection: An Update 
Annals of internal medicine  2008;149(3):177-184.
Background
Interferon-γ–release assays (IGRAs) are alternatives to the tuberculin skin test (TST). A recent meta-analysis showed that IGRAs have high specificity, even among populations that have received bacille Calmette–Guérin (BCG) vaccination. Sensitivity was suboptimal for TST and IGRAs.
Purpose
To incorporate newly reported evidence from 20 studies into an updated meta-analysis on the sensitivity and specificity of IGRAs.
Data Sources
PubMed was searched through 31 March 2008, and citations of all original articles, guidelines, and reviews for studies published in English were reviewed.
Study Selection
Studies that evaluated QuantiFERON-TB Gold, QuantiFERON-TB Gold In-Tube (both from Cellestis, Victoria, Australia), and T-SPOT.TB (Oxford Immunotec, Oxford, United Kingdom) or its precommercial ELISpot version, when data on the commercial version were lacking. For assessing sensitivity, the study sample had to have microbiologically confirmed active tuberculosis. For assessing specificity, the sample had to comprise healthy, low-risk individuals without known exposure to tuberculosis. Studies with fewer than 10 participants and those that included only immunocompromised participants were excluded.
Data Extraction
One reviewer abstracted data on participant characteristics, test characteristics, and test performance from 38 studies; these data were double-checked by a second reviewer. The original investigators were contacted for additional information when necessary.
Data Synthesis
A fixed-effects meta-analysis with correction for overdispersion was done to pool data within prespecified subgroups. The pooled sensitivity was 78% (95% CI, 73% to 82%) for QuantiFERON-TB Gold, 70% (CI, 63% to 78%) for QuantiFERON-TB Gold In-Tube, and 90% (CI, 86% to 93%) for T-SPOT.TB. The pooled specificity for both QuantiFERON tests was 99% among non–BCG-vaccinated participants (CI, 98% to 100%) and 96% (CI, 94% to 98%) among BCG-vaccinated participants. The pooled specificity of T-SPOT.TB (including its precommercial ELISpot version) was 93% (CI, 86% to 100%). Tuberculin skin test results were heterogeneous, but specificity in non–BCG-vaccinated participants was consistently high (97% [CI, 95% to 99%]).
Limitations
Most studies were small and had limitations, including no gold standard for diagnosing latent tuberculosis and variable TST methods and cutoff values. Data on the specificity of the commercial T-SPOT.TB assay were limited.
Conclusion
The IGRAs, especially QuantiFERON-TB Gold and QuantiFERON-TB Gold In-Tube, have excellent specificity that is unaffected by BCG vaccination. Tuberculin skin test specificity is high in non–BCG-vaccinated populations but low and variable in BCG-vaccinated populations. Sensitivity of IGRAs and TST is not consistent across tests and populations, but T-SPOT.TB appears to be more sensitive than both QuantiFERON tests and TST.
PMCID: PMC2951987  PMID: 18593687 CAMSID: cams235
24.  Interferon-gamma release assay as a diagnostic test for tuberculosis-associated uveitis 
Eye  2012;26(5):658-665.
Background
To study the use of interferon-gamma release assay (IFN-γ) (IGRAs) as a diagnostic test for tuberculosis (TB)-associated uveitis (TAU).
Design
Prospective cohort study.
Participants
Consecutive new patients (n=162) with clinical ocular signs suggestive of TAU, seen >1 year period at a single tertiary center.
Methods
All subjects underwent investigations to rule out underlying disease, including T-SPOT.TB and tuberculin skin test (TST). Twenty-one subjects with underlying disease and three with interdeterminate T-SPOT.TB results were excluded. Those with T-SPOT.TB- or TST-positive results were referred to infectious diseases physician for evaluation. Anti-TB therapy (ATT) was prescribed if required. Patients' treatment response and recurrence were monitored for six months after completion of ATT, if given; or 1 year if no ATT was given.
Main outcome measure
Diagnosis of TAU.
Results
Mean age of study cohort (n=138) was 46.8±15.3 years. Majority were Chinese (n=80, 58.0%) and female (n=75, 54.3%). TST was more sensitive than T-SPOT.TB (72.0% vs36.0%); but T-SPOT.TB was more specific (75.0% vs51.1%) for diagnosing TAU. Patients with either a T-SPOT.TB (1.44; 95% confidence intervals (CI), 0.86–2.42) or TST (1.47; 95% CI, 1.12–1.94)-positive result are more likely to have TAU. The accuracy of diagnosing TAU increases when both tests are used in combination (area under the receiver operator curve=0.665; 95% CI, 0.533–0.795). Patients with both tests positive are 2.16 (95% CI, 1.23–3.80) times more likely to have TAU. Negative T-SPOT.TB or TST results do not exclude TAU (negative likelihood ratios <1.0).
Conclusions
We recommend using a combination of clinical signs, IGRA, and TST to diagnose TAU.
doi:10.1038/eye.2012.1
PMCID: PMC3351054  PMID: 22302066
tuberculosis; uveitis; interferon-gamma release assay
25.  Diagnostic Performance of Interferon-Gamma Releasing Assay in HIV-Infected Patients in China 
PLoS ONE  2013;8(8):e70957.
Background
Active tuberculosis infection represents a very common and significant threat to HIV-infected patients. But measures to accurately detect it are limited.
Objective
To compare and analyze the diagnostic efficacy of T-SPOT.TB alone and in combination with TST in HIV-infected patients in China.
Method
TST (tuberculin skin test) and T-SPOT.TB were performed on 131 HIV-infected patients admitted in Beijing You’an Hospital and Beijing Ditan Hospital between Oct, 2010 and Jul, 2012, who were initially diagnosed as suspected ATB (active TB). The patients were further categorized into ATB and Not ATB based on clinical and cultural evidences. The performance of TST and T-SPOT.TB were analyzed and compared.
Results
The sensitivity and specificity of T-SPOT.TB were 41.3% and 94.6%, respectively, both higher than TST (12.9% and 91.8%). By combining T-SPOT.TB and TST, the sensitivity did not increase, but specificity was elevated to 100%. TST, T-SPOT.TB and their combinations all performed better in patients with extra-pulmonary diseases than with pulmonary disorders. False-positive T-SPOT.TB results were found to be associated with history of prior TB. In addition, concomitant bacterial infections and low CD4 counts were associated with increased ATB risk.
Conclusions
T-SPOT.TB is superior in screening ATB in HIV-infected patients in China over traditional TST. Additional TST would help to confirm a positive T-SPOT.TB result. Both tests work better for patients with extra-pulmonary conditions.
doi:10.1371/journal.pone.0070957
PMCID: PMC3732257  PMID: 23936478

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