Sensitivity Of Tuberculin Skin Test Research Articles

Role of the QuantiFERON®-TB Gold In-Tube test in the diagnosis of intrathoracic childhood tuberculosis

Tertiary care hospitals in India. To compare the performance of the QuantiFERON®-TB Gold In-Tube test (QFT-GIT) with that of the tuberculin skin test (TST) in the diagnosis of intrathoracic childhood tuberculosis (TB). Children with intrathoracic TB were enrolled in a randomised controlled trial studying micronutrient supplementation in intrathoracic TB. They underwent TST and QFT-GIT before starting daily anti-tuberculosis treatment. Of 362 children (median age 115.5 months, IQR 73-144, 55% girls) enrolled in the study, microbiological confirmation of TB was obtained in 128 (35%). The TST was positive in 337 (93%, 95%CI 90-95.5) and QFT-GIT in 297 (82%, 95%CI 77.8-85.6). Sensitivity of TST and QFT-GIT in culture-confirmed TB cases was respectively 90.5% (95%CI 84.1-94.5) and 82.6% (95%CI 74.9-88.4). QFT-GIT positivity rate correlated with TST induration (P < 0.001). TST was influenced by the disease spectrum (P = 0.004) and the age of the children (P = 0.002); QFT-GIT remained unaffected by these factors. Bacille Calmette-Guérin immunisation status, weight-for-age Z-scores and microbiological confirmation of Mycobacterium tuberculosis did not influence the performance of either test. In high-burden countries, QFT-GIT is comparable to TST and offers no added advantage in the diagnosis of childhood intrathoracic TB.

AB0518 High percentage of dermoconversion in patients with rheumatoid arthritis under biological therapy

BackgroundMexico is a high burden tuberculosis (Tb) country. Inflammatory rheumatic diseases such as rheumatoid arthritis have an increased risk of Tb associated with both RA activity itself and treatment requirement,...

English

BACKGROUND: HIV & Tuberculosis is a common co- infection that we come across in developing countries. Diagnosis is done by demonstration of acid fast bacilli (AFB) &Tuberculin skin test (TST). Skin test depends on cell mediated immune response which is generally compromised in HIV infected. OBJECTIVE: To compare the demonstration of AFB &TST reactivity in tuberculosis patients who are HIV seropositive & seronegative MATERIALS & METHODS: The study was conducted in the tuberculosis hospital which is attached to the Mysore medical college, Mysore. All patients clinically suspected or diagnostically confirmed as pulmonary tuberculosis were subjected for HIV screening test as per NACO guidelines .Total of 200 patients included for the study out of which 100 each were HIV seropositive & seronegative. They were subjected for microscopic examination of sputum& TST. Sputum microscopy was performed as per RNTCP guidelines. PPD antigen was injected intra- dermally on the left forearm & read after 48 hours & results were noted down. RESULTS: Study group divided into two categories. Category A: Pulmonary tuberculosis patients with HIV seropositivity Category B: Pulmonary tuberculosis patients with HIV seronegativity. Male preponderance was observed in both 79% & 70% with the mean age of 32.7 ± 7.3 years, in females seronegativity was more i.e.30% compared to 21% in seropositive with mean age of 29.3 ± 5.6 years. AFB demonstrated by Sputum microscopy in 99% HIV seronegatives & 54% of HIV seropositives. TST results classified into groups with No response, induration of 1-5mm,6-9mm & >10mm. Among category A 9 of them exhibited No response,32 of them 1-5mm,27 of them 6-9mm & 32 of them >10mm.All category B has responded to TST with only one patient with 1-5mm,25 with 6-9mm,74 with >10mm. DISCUSSION: There is statistically significant difference (p>0.05) in TST &AFB demonstration in pulmonary tuberculosis patients with HIV seropositive & seronegative. Sensitivity of TST is reduced as TST is indicator of cell mediated immune response which is generally compromised in HIV seropositive. Demonstration of AFB is also reduced in HIV seropositive cases. CONCLUSION: TST & demonstration of AFB are common tests done to screen for HIV-TB co infection in HIV seropositive. As the sensitivity of these tests are reduced in HIV seropositive it needs to be interpreted with care.

Screening for TB in high school adolescents in a high burden setting in South Africa

Screening for tuberculosis (TB) disease is important for TB control and TB vaccine efficacy trials but this has not been evaluated in adolescents. We conducted a study to determine the prevalence of active TB and performance of specific screening tests for TB in adolescents in a high burden setting. Adolescents aged 12-18 years were recruited from high schools in a rural town in South Africa. Participants were screened for active TB using symptoms, household TB contact, positive interferon gamma release assay (IGRA) and positive tuberculin skin test (TST). Of 6363 adolescents recruited, 21 were newly diagnosed with TB of whom 19 were culture positive. After exclusions, the derived prevalence of smear positive TB was 16/5682 = 3/1000 (95% confidence interval (CI) 1-4/1000). The sensitivity of TST and IGRA for active TB were 85% (95% CI 62-100%) and 94% (95% CI 79-100%) respectively. None of the methods alone or in combination had positive predictive values greater than 2%. The screening tools evaluated in this study may not be practical for routine use owing to low positive predictive values but may be useful in TB vaccine clinical trials.

Interferon-gamma release assays for the diagnosis of extrapulmonary tuberculosis: a systematic review and meta-analysis

Interferon -gamma release assays (IGRAs) provide a new diagnostic method for Mycobacterium tuberculosis (TB) infection. However, the diagnostic value of IGRAs for extrapulmonary TB (EPTB) has not been clarified. We searched several databases and selected papers with strict inclusion criteria, evaluated the evidence of commercially available IGRAs (QuantiFERON(®) -TB Gold QFT-G or QFT-GIT and T-SPOT(®) .TB) on blood and the tuberculin skin test (TST) using random effects models. Twenty studies with 1711 patients were included. After excluding indeterminate results, pooled sensitivity for the diagnosis of EPTB was 72% [95% confidence interval (CI) 65-79%] for QFT-G or GIT and 90% (95% CI, 86-93%) for T-SPOT; in high-income countries the sensitivity of QFT-G or GIT (79%, 95% CI 72-86%) was much higher than that (29%, 95% CI 14-48%) in low/middle-income countries. Pooled specificity for EPTB was 82% (95% CI 78-87%) for QFT-G or GIT and 68% (95% CI 64-73%) for T-SPOT. Pooled sensitivity of TST from four studies in high-income countries was lower than that of IGRAs. T-SPOT was more sensitive in detecting EPTB than QFT-G or GIT and TST. However, both IGRAs and TST have similar specificity for EPTB. IGRAs have limited value as diagnostic tools to screen and rule out EPTB, especially in low/middle-income countries. The immune status of patients does not affect the diagnostic accuracy of IGRAs for EPTB.

Interferon-Γ Release Assays for the Diagnosis and Mycobacterium Tuberculosis Infection in Children: A Systematic Review and Meta-Analysis

Data regarding the use of interferon-gamma release assays (IGRAs) for tuberculosis diagnosis are accumulating. We systematically searched PubMed, EMBASE and Cochrane and performed pooled estimates of sensitivity and specificity of QuantiFERON-TB Gold In Tube (QFT-G-IT) and T-SPOT.TB compared to tuberculin skin test (TST). For studies assessing sensitivity, children had to have active tuberculosis. Specificity data were derived from children classified as non-infected. Eleven studies were included in the sensitivity analysis for TST, 10 for QFT-G-IT, and 9 for T-SPOT.TB. Eight studies were included in specificity analysis for TST, 8 for QFT-G-IT, and 7 for T-SPOT.TB. Pooled QFT-G-IT sensitivity was 0.79 (95% CI:0.70-0.89) pooled T-SPOT.TB sensitivity was 0.74 (95% CI:0.59-0.90) and pooled TST sensitivity was 0.82 (95% CI:0.72-0.93). Pooled QFT-G-IT and T-SPOT.TB specificities were 0.95 (95% CI:0.93- 0.97) and 0.96 (95% CI:0.93-1.00), respectively. Pooled TST specificity was significantly lower 0.83 (95% CI:0.74-0.92). IGRA performance in children showed no better sensitivity than TST, but higher specificity.

Tuberculin reactivity in first‐year schoolchildren in Madagascar

The tuberculin skin test (TST) is an important tool in the diagnosis of tuberculosis infection in children. However, the interpretation of TST may be complicated by prior Bacillus Calmette-Guerin (BCG) vaccination. We evaluated the effect of vaccination with BCG on TST reactivity in first-year pupils attending state schools in Antananarivo. STs were performed on 376 first-year schoolchildren, aged 6 and 7, attending two state primary schools. The relationships between epidemiological information, BCG status (vaccination, BCG scars) and TST reactivity were assessed to compare TST sensitivity between children with and without BCG vaccination and between those with and without a BCG scar. The prevalence of positive TST results of ≥5, ≥10 and ≥ 15 mm was 20.2% (76/376), 18.3% (69/376) and 11.4% (43/376), respectively. BCG vaccination was not associated with TST reactivity, whatever the threshold used: ≥5 mm (odds ratio (OR, 1.2; 95% confidence interval (CI), 0.7-2.0); ≥10 mm (OR, 0.9; 95% CI, 0.6-1.7); ≥15 mm (OR, 0.6; 95% CI, 0.3-1.2). These results suggest that in Madagascar, a positive TST result indicates TB infection (active or latent) rather than past BCG vaccination. Therefore, high BCG vaccination coverage does not appear to impair the usefulness of the TST as a tool for diagnosing tuberculosis.

Interferon-Gamma Release Assay Performance in Pulmonary and Extrapulmonary Tuberculosis

BackgroundThe 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 FindingsTwo 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.ConclusionsIGRA 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.

Tuberculin reactivity in bacille calmette-guerin vaccinated individuals with sputum positive pulmonary tuberculosis

The study was carried out to assess the value of tuberculin skin test for the diagnosis of Tuberculosis (TB) in BCG vaccinated individuals and to find out the sensitivity rate of tuberculin skin test (TST) in comparison to acid fast bacilli positive pulmonary TB. Similar population with high BCG vaccination coverage having both pulmonary TB patients (n=150) and apparently healthy individuals (n=150) in eastern Nepal were enrolled in this comparative study. Sputum from all the subjects was subjected to Z-N microscopy. TST was performed on these subjects by standard Mantoux method. Among the patients (mean age 36.18±14.15 yrs) and controls (mean age 35.61±13.44 yrs), 55.33 % and 47.33 % respectively have been found to be positive PPD reactors (&gt;10mm) which is statistically not significant (P&gt;0.05). About 23% of the patients &amp; 27% of controls failed to react (anergic) to 5 TU PPD. PPD reactivity rate was high in the patients whose sputum smears were graded as 1+ in Z-N microscopy. The sensitivity of TST was highest for the induration of &gt;5mm (77.3%). Specificity increased with increasing size of induration and was highest (73.3%) with induration of &gt;15 mm. Tuberculin skin test is an all or none phenomenon. In Nepal, tuberculin test has a limited value in the diagnosis of pulmonary TB as both the apparently healthy individuals and patients with sputum smear positive pulmonary TB who had been immunized with BCG, showed almost similar rate of tuberculin reactivity. DOI: http://dx.doi.org/10.3126/jcmsn.v7i1.5970 JCMSN 2011; 7(1): 28-35

Tuberculin skin test and QuantiFERON® assay in young children investigated for tuberculosis in South Africa

Although the literature on interferon-gamma release assays on tuberculosis (TB) in children has increased, data pertaining to young children remain relatively limited. To compare results from the tuberculin skin test (TST) and the QuantiFERON®-TB Gold In-Tube assay (QFT) in children aged <3 years investigated for TB disease. TB suspects were evaluated by medical history and examination, TST, QFT, chest radiography, induced sputum and gastric washings for smear and culture for Mycobacterium tuberculosis. A total of 400 children were enrolled. Among 397 children with both test results, 68 (17%) were QFT-positive and 72 (18%) were TST-positive (≥10 mm). Agreement between the tests was excellent (94%, κ = 0.79, 95%CI 0.69-0.89). TB disease was diagnosed in 52/397 (13%) participants: 3 definite, 35 probable and 14 possible TB. QFT sensitivity and specificity for TB disease were respectively 38% and 81%. TST sensitivity and specificity were respectively 35% and 84%. While TST and QFT had excellent concordance in this population, both tests had much lower sensitivity for TB disease than has been reported for other age groups. Our results suggested equivalent performance of QFT and TST in the diagnosis of TB disease in young children in a high-burden setting.

Amendment of tuberculosis prevention law and prospect of tuberculosis control program

Amendment of tuberculosis prevention law and prospect of tuberculosis control program

Comparing the Tuberculin Skin Test and T-SPOT.TB Blood Test in Children

Interferon-γ-release assays (IGRAs) have been developed for the diagnosis of tuberculosis infection, but few data are available for children. There currently is no reference standard for the diagnosis of tuberculosis infection. To compare the performance of 1 IGRA, the T-SPOT.TB assay with the tuberculin skin test (TST) in children with different epidemiologic risk factors for tuberculosis. We conducted a prospective study of 210 patients referred to 3 pediatric tuberculosis clinics, including those with no risk factors for tuberculosis (low risk, n = 27), risk factors but no identifiable source case (intermediate risk, n = 78), contact with a known source case (high risk, n = 74), and active disease (n = 31). Children were tested with TST and T-SPOT.TB. Concordance analyses were performed, and assay outcomes were modeled by multivariate logistic regression. For 13 children with culture-confirmed tuberculosis disease, sensitivity of TST and T-SPOT.TB was 77% and 92%, respectively, and concordance was 69%. For high-risk children, concordance was 94% for BCG-unimmunized children and 88% for BCG-immunized children. For intermediate-risk children, concordance was 74% for BCG-unimmunized children and 33% for BCG-immunized children. For low-risk children, concordance was 74% for BCG-unimmunized children and 20% for BCG-immunized children. Multivariate analysis revealed that contact with a source case was associated with T-SPOT.TB result, but age and BCG immunization were not. T-SPOT.TB is comparable to the TST in the diagnosis of tuberculosis disease and identification of high-risk children with tuberculosis infection and is more specific than the TST in children who have received the BCG vaccine.

Use of the T-spot.TB test for the diagnosis of latent tuberculosis infection

Background:Tuberculosis (TB) represents a major health problem both in developing and both in industrialized countries.The identification of individuals latently infected with Mycobacterium tuberculosis (Mtb) play a key role for the efficacy of TB control. These individuals with a latent tuberculosis infection (LTBI), especially those with high risk of reactivation (e.g. HIV + / AIDS-infected individuals, patients undergoing immunosuppressive therapy and children younger than 5 years) could benefit from a preventive treatment with isoniazid reducing the risk of progression from LTBI to active TB. Until recently, detection of LTBI has relied on the tuberculin skin test (TST), but despite the widespread use in clinical practice,TST does not reliably diagnose LTBI because several drawbacks, e.g. lacking in specificity, particularly in who were exposed to non-tuberculous mycobacteria (NTM) or were vaccinated with Bacille Calmette-Guerin (BCG) In addition, in young subjects,TST sensitivity is hampered by impaired T cell function leading frequently to false negative results.These several drawbacks limit the use of TST for the diagnose an LTBI in patients who may benefit from preventive chemotherapy. On the other hand, an accurate diagnosis of LTBI avoid the over-treatment of those patients with a positive TST results but not latently infected with Mtb. Recently, new tests based on the detection of interferon-gamma (IFN-γ) after stimulation with Mtb-specific antigens: Early secretory Antigenic Target-6 (ESAT-6) and Culture Filtrate Protein-10 (CFP-10) have been proposed for the diagnosis of active TB and LTBI. Methods: During the period from January 2009 to June 2009, in our laboratory 70 patients were tested with T-SPOT.TB (Oxford Immunotech, Abingdon, United Kingdom).We enrolled transplant patients and subjects ongoing transplant, patients immigrants from high prevalence TB countries, patients screened for immunosuppressive treatment, HIV / AIDS – infected individuals.We also tested 3 patients with clinical / radiological suspicion of active TB and 3 patients with positive tuberculin skin test and with a positive direct examination for mycobacteria in the urinary sediment. Results: In 2 patients with symptoms suggestive of TB in place,T-SPOT.TB showed a higher response of (IFN-g), more than 100 spots.Among individuals ongoing renal transplant, 6 patients tested T-SPOT.TB positive and 4 subjects were T.SPOT.TB -negative. Two patients with an autoimmune disease showed an high response to Mtb-specific antigens with T-SPOT.TB test tested before to start any treatment.T-SPOT.TB test tested strongly negative in 4 paediatric patients and in one HIV-infected individuals, regardless a positive response to a internal positive response (phytohaemagglutinin (PHA), suggesting a normal immune response. Conclusions:This preliminary data suggest that the T.SPOT.TB showed high sensitivity and specificity, producing a strongly negative response to Mtb-specific antigens in subjects who had a history of previous BCG-vaccination. In addition, T-SPOT.TB test provides, unlike the TST, indication about the potential immunosuppression of tested patient with an internal positive control that can highlight the production of IFN- γ by lymphocytes resulting in the application of this test in immunocompromised patients, e.g. children and transplantated patients and others.

Evidence-Based Comparison of Commercial Interferon-γ Release Assays for Detecting Active TB: A Metaanalysis

Test accuracy of interferon-gamma release assays (IGRAs) for diagnosing TB differs when using older or precommercial tools and inconsistent diagnostic criteria. This metaanalysis critically appraises studies investigating sensitivity and specificity of the commercial T-Spot.TB and the QuantiFERON-TB Gold In-Tube Assay (QFT-IT) among definitely confirmed TB cases. We searched Medline, EMBASE, and Cochrane bibliographies of relevant articles. Sensitivities, specificities, and indeterminate rates were pooled using a fixed effect model. Sensitivity of the tuberculin skin test (TST) was evaluated in the context of IGRA studies. In addition, the rates of indeterminates of both IGRAs were assessed. The pooled sensitivity of TST was 70% (95% CI, 0.67-0.72) compared with 81% (95% CI, 0.78-0.83) for the QFT-IT and 88% (95% CI, 0.85-0.90) for the T-Spot.TB. Sensitivity increased to 84% (95%CI, 0.81-0.87) and 89% (95% CI, 0.86-0.91) for the QFT-IT and T-Spot.TB, respectively, when restricted to performance in developed countries. In contrast, specificity of the QFT-IT was 99% (95% CI, 0.98-1.00) vs 86% for the T-Spot.TB (95% CI, 0.81-0.90). The pooled rate of indeterminate results was low, 2.1% (95% CI, 0.02-0.023) for the QFT-IT and 3.8% (95% CI, 0.035-0.042) for the T-Spot.TB, increasing to 4.4% (95% CI, 0.039-0.05) and 6.1% (95% CI, 0.052-0.071), respectively, among immunosuppressed hosts. The newest commercial IGRAs are superior, in comparison with the TST, for detecting confirmed active TB disease, especially when performed in developed countries.

Comparison of interferon-γ release assays and tuberculin skin test in predicting active tuberculosis (TB) in children in the UK: a paediatric TB network study

BackgroundThe value of interferon-γ release assays (IGRA) to diagnose active tuberculosis (TB) in children is not established, but these assays are being widely used for this purpose. The authors examined...

Role of Interferon Gamma Release Assay in Active TB Diagnosis among HIV Infected Individuals

BackgroundA rapid and specific test is urgently needed for tuberculosis (TB) diagnosis especially among human immunodeficiency virus (HIV) infected individuals. In this study, we assessed the sensitivity of Interferon gamma release assay (IGRA) in active tuberculosis patients who were positive for HIV infection and compared it with that of tuberculin skin test (TST).Methodology/Principal FindingsA total of 105 HIV-TB patients who were naïve for anti tuberculosis and anti retroviral therapy were included for this study out of which 53 (50%) were culture positive. Of 105 tested, QuantiFERON-TB Gold in-tube (QFT-G) was positive in 65% (95% CI: 56% to 74%), negative in 18% (95% CI: 11% to 25%) and indeterminate in 17% (95% CI: 10% to 24%) of patients. The sensitivity of QFT-G remained similar in pulmonary TB and extra-pulmonary TB patients. The QFT-G positivity was not affected by low CD4 count, but it often gave indeterminate results especially in individuals with CD4 count <200 cells/µl. All of the QFT-G indeterminate patients whose sputum culture were positive, showed ≤0.25 IU/ml of IFN-γ response to phytohemagglutinin (PHA). TST was performed in all the 105 patients and yielded the sensitivity of 31% (95% CI: 40% to 22%). All the TST positives were QFT-G positives. The sensitivity of TST was decreased, when CD4 cell counts declined.Conclusions/SignificanceOur study shows neither QFT-G alone or in combination with TST can be used to exclude the suspicion of active TB disease. However, unlike TST, QFT-G yielded fewer false negative results even in individuals with low CD4 count. The low PHA cut-off point for indeterminate results suggested in this study (≤0.25 IU/ml) may improve the proportion of valid QFT-G results.

Comparison of Interferon-Gamma Release Assay Versus Tuberculin Skin Test for Tuberculosis Screening in Inflammatory Bowel Disease

Comparison of Interferon-Gamma Release Assay Versus Tuberculin Skin Test for Tuberculosis Screening in Inflammatory Bowel Disease

Use of T Cell–Based Diagnosis of Tuberculosis Infection to Optimize Interpretation of Tuberculin Skin Testing for Child Tuberculosis Contacts

Treatment of recent tuberculosis infection in children aged <2 years is essential, because of high risk of progression to disease, but diagnosis is hindered by the inaccuracy of the tuberculin skin test (TST). More-accurate T cell-based tests of infection could enhance diagnosis by optimizing interpretation of the TST results. A total of 979 child tuberculosis contacts in Istanbul underwent the TST and enzyme-linked immunospot assay. Using enzyme-linked immunospot test results as a reference standard, we assessed the effect of age and bacille Calmette-Guérin (BCG) vaccination on the sensitivity and specificity of the TST, and we computed the optimal TST cutoff points, using receiver operating characteristic curves. With a TST cutoff point of >or=10 mm, the sensitivity of the TST was 66% for children aged <2 years, which was lower than that for older children (P= .006). Specificity was 75% for BCG-vaccinated children, compared with 92% for unvaccinated children (P= .001). Optimal cutoff points improved TST specificity for children with 1 BCG scar, with little loss of sensitivity. Despite the use of optimal cutoff points, TST sensitivity remained <70% for children aged <2 years, specificity remained <87% for BCG-vaccinated children aged >or=2 years, and overall accuracy was low for children with >1 BCG scar. Negative results of the TST cannot exclude tuberculosis infection for child tuberculosis contacts aged <2 years, which supports the use of preventive therapy regardless of the TST results for this age group. In children aged >or=2 years, the accuracy of the TST can be improved by adjustment of cutoff points for BCG-vaccinated children but remains poor for children with >1 BCG scar. This methodology can define optimal TST cutoff points for diagnosis of tuberculosis infection tailored to target populations.

Accuracy of Immunodiagnostic Tests for Active Tuberculosis Using Single and Combined Results: A Multicenter TBNET-Study

BackgroundThe 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 Findings425 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.ConclusionsThe 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.

Tuberculin Skin Testing in Patients with HIV Infection: Limited Benefit of Reduced Cutoff Values

When determining eligibility for isoniazid preventive therapy of human immunodeficiency virus (HIV)-infected patients, the cutoff value of the tuberculin skin test (TST) is often reduced from an induration of 10 mm in diameter to one of 5 mm in diameter to compensate for loss of sensitivity. The effectiveness of this reduction depends on the underlying mechanism: a gradual decrease in skin test responsiveness with decreasing immunocompetence or an all-or-nothing switch to complete anergy. No published studies have assessed this directly in patients with tuberculosis. We performed a cross-sectional study of TST responses and HIV infection among patients with sputum smear-positive pulmonary tuberculosis in 6 hospitals in Tanzania. Skin test anergy was defined as a TST reaction < or =2 mm in diameter. Of 991 patients with complete results, 451 (45.5%) had HIV infection. Anergy was observed in 111 (24.6%) of 451 HIV-infected patients and 18 (3.3%) of 540 HIV-uninfected patients (P<.001). The reaction size distributions among nonanergic HIV-infected and uninfected patients showed a limited difference (mean diameter +/- standard deviation, 15.9 +/- 5.0 mm and 16.8 +/- 3.8 mm, respectively; P=.048). The sensitivity of the TST among HIV-uninfected patients was 91.1% at a cutoff value of 10 mm and 95.2% at a cutoff value of 5 mm. The sensitivity of the TST among HIV-infected patients was 64.3% at a cutoff value of 10 mm and 71.2% at a cutoff value of 5 mm; the sensitivity of the TST was 67.6% and 74.5%, respectively, after adjustment for tuberculosis-specific anergy. In subjects with tuberculosis disease and HIV infection, loss of TST sensitivity is predominantly attributable to anergy (i.e., an all-or-nothing phenomenon). The decrease in the proportion of false-negative TST results obtained by reducing the cutoff value from 10 mm to 5 mm is limited.