Gold In-Tube Assay Research Articles

Comparative study between using QuantiFERON and tuberculin skin test in diagnosis of Mycobacterium tuberculosis infection

AimStudy degree of sensitivity and specificity of IFN-γ as QuantiFERON-TB Gold In-Tube assay in diagnosis of tuberculosis instead of tuberculin test. Subjects and methodsForty patients were included in this study subdivided into two groups. First included 20 patients with sputum positive for tuberculosis, while the second included 20 patients suspected to catch TB infection, guided by: clinical and radiological examinations with smear negative for TB. Control group included 10 clinical and radiological healthy controls previously vaccinated by BCG with positive tuberculin test. All subjects were submitted for full clinical history physical examination routine laboratory tests, plain chest X-ray, sputum study for acid fast Bacilli by Ziehl–Neelsen stain, tuberculin test using Mantoux technique, sputum culture on Lowenstein-Jensen Medium and QuantiFERON-TB Gold In-Tube (QFT-Gold IT) assay. ResultsQFT-Gold IT test sensitivity=100% specificity=100% predictive value positive=100% which means that 100% of the disease positive patients gave positive QFT-Gold IT test and predictive value negative=100% which means that 100% of the disease negative patients gave negative QFT-Gold IT test. Agreement between tuberculin test and QFT-Gold IT test was good agreement where the ‘κ’ was 0.65 (CI=0.39–0.91). Study revealed positive correlation between QuantiFERON level and severity of infection in sputum, which was statistically significant, where ‘r’ was 0.92 and P-value was <0.05. ConclusionQFT-Gold IT, has excellent sensitivity and specificity unaffected by BCG vaccination. Tuberculin test specificity is high in non-BCG-vaccinated populations but low and variable in BCG vaccinated populations.

Prevalence of Latent Tuberculosis Infection among Health Care Workers in South Korea: A Multicenter Study

BackgroundWe investigated the prevalence of latent tuberculosis infection (LTBI) among the health care workers (HCWs) and analyzed its risk factors in South Korea.MethodsA standard questionnaire regarding the baseline demographics and risk factors for LTBI was given to each participant and tuberculin skin test (TST), QuantiFERON-TB GOLD In-Tube (QFT-GIT) assay, and chest radiography were performed.ResultsA total of 493 participants, 152 (30.8%) doctors and 341 (69.2%) nurses were enrolled in eight tertiary referral hospitals. The mean age of the subjects was 30.6 years old, and 383 (77.7%) were female. Of the 152 doctors, 63 (41.4%) and 36 (23.7%) were positive by TST and by QTF-GIT, respectively, and among the 341 nurses, 119 (34.9%) and 49 (14.4%) had positive TST and QFT-GIT results, respectively. Overall, the agreement between the two tests was 0.22 by the chance corrected proportional agreement rate (kappa coefficient) in 493 subjects. Experience of working in tuberculosis (TB)-related departments was significantly associated with positive LTBI test results by QFT-GIT assay, not by TST. In multivariate analysis, only age was independently associated with increased risk of a positive TST result, while age and experience of working in TB-related departments (odds ratio, 2.29; 95% confidence interval, 1.01-5.12) were independently associated with increased risk of a positive QFT-GIT result.ConclusionA high prevalence of LTBI was found among South Korean HCWs. Considering the association between the experience of working in TB-related departments and high risk of LTBI, QFT-GIT may be a better diagnostic test for LTBI than TST in HCWs.

Simultaneous and Longitudinal Comparison of Interferon Gamma Release Assay Data from Health Care Workers in Japan

Background: Tuberculosis is one of the serious occupational diseases among health care workers, especially those who work with patients suffering from respiratory disorders. It is important to assess latent tuberculosis infection status in such workers using interferon- release assays, including QuantiFERON-TB Gold and its successor, the QuantiFERON-TB Gold in-Tube test. Although the relative efficacies of these two methods have been evaluated in patients with tuberculosis, data from health care workers in Japan have not been extensively examined. Purpose: In the present study, we examined the utilities of the QuantiFERON-TB Gold and QuantiFERON-TB Gold in-Tube tests to detect latent tuberculosis infections in staff working in a respiratory disease hospital in Japan. We also longitudinally compared data from these subjects obtained using the QuantiFERON-TB Gold assay. Methods: We collected blood samples from 120 staff members and performed both the QuantiFERON-TB Gold and QuantiFERON-TB Gold in-Tube assays. A total of 58 subjects had previously been tested 5 years prior using the QuantiFERON-TB Gold assay, and we compared these data with our more recent information. Results: The QuantiFERON-TB Gold in-Tube test tended to yield higher test values than did the QuantiFERONTB Gold test, suggesting that the former test may be more sensitive when used to detect latent tuberculosis infection. In both tests, the results differed in 32 instances (26.7%), associated with significant difference (p<0.001, =0.55). In 94 subjects with negative QuantiFERON-TB Gold test results, 16 (17.0%) were intermediate and 11 (11.7%) positive by QuantiFERON-TB Gold in-Tube test. The longitudinal comparison confirmed this suggestion. The number of subjects rated “intermediate” in terms of tuberculosis status differed, with statistical significance, when the two datasets were compared. Conclusion: Health care workers should be screened for possible tuberculosis infections using the QuantiFERON-TB Gold in-Tube test, which is more sensitive than the QuantiFERON-TB Gold test.

Identification of False-Positive QuantiFERON-TB Gold In-Tube Assays by Repeat Testing in HIV-Infected Patients at Low Risk for Tuberculosis

Identification of False-Positive QuantiFERON-TB Gold In-Tube Assays by Repeat Testing in HIV-Infected Patients at Low Risk for Tuberculosis

Evaluation of the diagnostic potential of IP-10 and IL-2 as biomarkers for the diagnosis of active and latent tuberculosis in a BCG-vaccinated population.

BackgroundThe Mycobacterium tuberculosis (Mtb)-specific T-cell interferon gamma release assays (IGRAs) are useful in detecting Mtb infection but perform poorly at distinguishing active tuberculosis disease (ATB) and latent tuberculosis infection (LTBI). This study is aimed at evaluating additional cytokines as biomarkers besides interferon-gamma (IFN-γ) to improve the identification of ATB and LTBI.Methodology/Principal FindingsSixty-six patients with ATB, 73 household contacts (HHC) of ATB patients and 76 healthy controls (HC) were recruited to undergo QuantiFERON TB GOLD in-tube assay (QFT) and the enzyme-linked immunosorbent assay (ELISA) where the release of IFN-γ, IFN-γ inducible protein 10 (IP-10), Interleukin 2 (IL-2) and Tumor Necrosis Factor-α (TNF-α) was determined in the whole blood with or without antigen-stimulation. The positive rates of the QFT, IP-10 and IL-2 tests were 86.4%, 89.4% and 86.4% for the ATB group with no difference between them (p>0.05). However, QFT in combination with IP-10 and IL-2 significantly increased the detection rate to 95.5% in the ATB group (p = 0.03) and the indeterminate rate of all samples decreased from 2.3% (5/215) to 0.4% (1/215). The un-stimulated level of IP-10 was significantly higher in the HHC than the ATB and HC groups. The IP-10 responses were strongly associated with extended Mtb exposure time and the degree of smear-positivity of the index cases. The IL-2/IFN-γ ratio in the antigen-stimulated plasma could discriminate LTBI from ATB with a sensitivity of 77.2% and a specificity of 87.2%.ConclusionThe increased Mtb-specific antigen-stimulated expression of IP-10 and IL-2 may be useful for detecting both ATB and LTBI. Combining the QFT with IP-10 and IL-2 could increase the detection accuracy of active TB over the QFT alone.

Monthly Follow-ups of Interferon-γ Release Assays Among Health-care Workers in Contact With Patients With TB

Interferon-γ (IFN-γ) release assays (IGRAs), which can overcome several limitations of the tuberculin skin test in detecting latent TB infection, were introduced recently in routine clinical practice. However, IGRAs are highly dynamic tests, and the T-cell responses tend to fluctuate over time. We wanted to evaluate the conversion and reversion rates of monthly IGRAs over 1 year among health-care workers (HCWs) in contact with patients with TB in South Korea, a country with an intermediate TB burden. Forty-nine HCWs in contact with patients with active pulmonary TB were prospectively enrolled. Interviews on exposure to patients with active TB, a physical examination, and a QuantiFERON TB Gold In-Tube assay (QFT-GIT) were carried out monthly for 1 year. Among 48 participants, 25 (52%) showed inconsistent results in serial testing. When an increase from< 0.35 IU/mL to ≥ 0.70 IU/mL was applied as the definition of a conversion, inconsistent IGRA results were identified in 13 participants (27.0%). Consistency in QFT-GIT results was associated with age, length of service, and baseline IFN-γ levels, but not with the profession of the participant, degree of TB exposure, or wearing of an N95 mask. In five participants, fluctuations in IFN-γ levels showed levels > 0.70 IU/mL two or more times. Fluctuation in IGRA findings was common when HCWs in contact with patients with TB were tested monthly. This could be a result of poor reproducibility of the assay, repeated infection and true reversion, or periodic secretion of antigens from Mycobacterium tuberculosis. ClinicalTrials.gov; No.: NCT01121068; URL: www.clinicaltrials.gov

Risk factors for &lt;I&gt;Mycobacterium tuberculosis&lt;/I&gt; infection in Indonesian children living with a sputum smear-positive case

Young children living with infectious tuberculosis (TB) cases are at high risk of infection and disease, and screening is recommended. This is rarely conducted in resource-limited settings. Identifying children most at risk of infection may be useful for setting practical screening policies. Child contacts of smear-positive adult TB patients were invited for Mycobacterium tuberculosis infection and disease screening by symptoms, tuberculin skin test (TST), QuantiFERON-TB Gold In-Tube assay (QFT-GIT) and chest X-ray. Risk factors for infection were collected using a questionnaire and were calculated separately for TST, for QFT-GIT and for both tests combined. Of 304 screened children 145/302 (48%) were positive using TST, 152/299 (51%) by QFT-GIT and 180/304 (59%) were positive using either or both tests. Positivity for both tests was associated with index case infectivity (acid-fast bacilli [AFB] 3+ vs. AFB 1+: TST OR 2.93, 95%CI 1.59-5.39; QFT-GIT OR 2.28, 95%CI 1.06-4.90) and exposure (child contact's parent is the index case: TST OR 7.04, 95%CI 2.23-22.28; QFT-GIT OR 4.30, 95%CI 1.48-12.45). M. tuberculosis infection according to either test was high, supporting screening and preventive treatment. Children of smear-positive TB cases who accompany their parents to the clinic should be prioritised for immediate screening.

Gamma Interferon Release Assay for Monitoring of Treatment Response for Active Tuberculosis: an Explosion in the Spaghetti Factory

Few studies have correlated the results of interferon (gamma interferon) release assays (IGRAs) with known markers of tuberculosis (TB) treatment response. We report the results of serial QuantiFERON-TB gold in-tube assay (QFT) testing on 149 patients with active tuberculosis and correlate the results with smear and culture conversion. We show that QFT results do not offer much value for treatment monitoring of TB disease.

Mycobacterium tuberculosis Region of Difference (RD) 2 Antigen Rv1985c and RD11 Antigen Rv3425 Have the Promising Potential To Distinguish Patients with Active Tuberculosis from M. bovis BCG-Vaccinated Individuals

Antigens encoded in the region of difference (RD) of Mycobacterium tuberculosis constitute a potential source of specific immunodiagnostic antigens for distinguishing tuberculosis (TB) infection from BCG vaccination. We evaluated the diagnostic potential of specific T-cell epitopes selected from two immunodominant antigens, Rv1985c and Rv3425, from RD2 and RD11, respectively, on the basis of epitope mapping, in TB patients and BCG-vaccinated healthy individuals. Using a whole-blood gamma interferon release assay, a wide array of epitopes was recognized on both Rv1985c and Rv3425 in TB patients. Those epitopes that could specifically discriminate TB infection from BCG vaccination were carefully selected, and the most promising peptide pools from Rv1985c showed a sensitivity of 53.9% and a specificity of 95.5%. When the novel specific peptides from Rv1985c joined the diagnostic antigens in the QuantiFERON-TB Gold In-Tube (QFT-IT) assay, the sensitivity was increased from 86.4% to 96.2%, with no drop in specificity. These results indicate that the peptide pools selected from Rv1985c and Rv3425 have the potential to diagnose TB infection by a method that may be routinely used in clinical laboratories.

The Responses of Multiple Cytokines Following Incubation of Whole Blood from TB Patients, Latently Infected Individuals and Controls with the TB Antigens ESAT‐6, CFP‐10 and TB7.7

The development of clinically relevant biomarkers is important for diagnosing latent tuberculosis infection (LTBI) and active tuberculosis (TB) and predicting their prognoses. This study examined whether the responses of multiple cytokines can be used as a biomarker to distinguish the TB infection status and mycobacterial load. We analysed the responses of multiple cytokines (IFN-γ, IL-2, IL-10, IL-13, IL-17 and TNF-α) in the supernatant from the QuantiFERON-TB Gold In-Tube assay following stimulation of whole blood from the TB group (n = 32), LTBI group (n = 19) and healthy controls (n = 30) with TB antigens (ESAT-6, CFP-10 and TB7.7). The median responses of IFN-γ, IL-2, IL-10 and IL-13 were higher in the LTBI and active TB groups than in the non-TB control group (IFN-γ, P < 0.001; IL-2, P < 0.001; IL-10, P = 0.012; IL-13, P < 0.001). The median IL-2/IFN-γ ratio of the LTBI group was higher than that of the active TB group (P = 0.014) and differed significantly between patients with LTBI, patients with smear-negative TB and patients with smear-positive TB (P = 0.027). This difference was especially evident between the patients with LTBI and patients with smear-positive TB (P = 0.047). In conclusion, IFN-γ, IL-2, IL-10 and IL-13 can serve as biomarkers for distinguishing TB infection. In addition, the IL-2/IFN-γ ratio appears to be a biomarker for diagnosing LTBI and may be useful as a prognostic factor and for evaluating treatment responses.

Interferon-gamma release assay: use and misuse

Interferon-gamma release assays are being increasingly used worldwide for the diagnosis of latent tuberculosis (TB) in patients of all ages, including children [1]. A PubMed search with ‘interferon-gamma release assays’ as keyword revealed a total of 1077 references, up to 100 of which had been released in 2012, including several reviews. In national and international guidelines such as CDC [2], ECDC [3], Canadian [4], French [5] and UK [6] guidelines, interferon-gamma release assays are used either in place of or in addition to the tuberculin skin test for latent TB diagnosis, indicating the lack of clear evidence regarding the use of interferon-gamma release assays. There are two major interferon-gamma release assays available: the quantiFERON-TB Gold in-Tube assay, which is an ELISA from Cellestis (Chadstone, Australia), and the T-SPOT.TB assay, which is an enzyme-linked immunospot assay from Oxford Immunotec (Abingdon, UK). The development of these tests opens to a fruitful market. ‘We now have market penetration about 2 million tests per year—about 1 QFT test every 15 seconds’ said Ron Pitcher in the Cellestis 2010 Annual Report (available at: http://www.cellestis.com/ IRM/Company/ShowPage.aspx?CPID= 1807E 850 tested positive with both tests, none were preventively treated, eight were finally diagnosed with active TB, and four others progressed to TB within 4–24 months [10]. In this study, the preventive treatment would have be given to 842 persons to prevent four active TB cases. This demonstrates the poor cost-effectiveness of systematic screening. However, in TB-exposed individuals, 2.3–14.6% of those with positive tuberculin skin test results or interferon-gamma release assay results, respectively, will develop active TB [11]. The main purpose of interferon-gamma release assays is to allow the treatment of patients with latent TB at risk of developing active TB, such as TB-exposed individuals or immunocompromised patients. Only patients who would benefit from preventive treatment should be tested. The decision to test presupposes a decision to treat if the test result is positive. Misuse: There is no indication for the use of these tests in systematic screening. Because the available evidence is currently inconsistent, interferon-gamma release assays should not be used to monitor response to TB therapy. Neither tuberculin skin tests nor interferon-gamma release assays can distinguish between active and latent infection, and for this reason the test is not accurate for the diagnosis of active TB [12], which relies on the identification of M. tuberculosis. Use: Typically, interferon-gamma release assays can be used in persons with an increased risk of new TB, such as asymptomatic person after close contact with an active case of pulmonary/respiratory TB, and in patients with an increased risk of TB reactivation, such as patients infected with human immunodeficiency virus, those with transplants, lymphoma, leukaemia, head and neck cancer, chemotherapy, or other therapeutic immunosuppression, and those who will be treated with tumour necrosis factor-a inhibitors.

Observational Study of QuantiFERON®-TB Gold In-Tube Assay in Tuberculosis Contacts in a Low Incidence Area

BackgroundQuantiFERON®-TB Gold in-Tube (QFT) assay is a recently developed test to assess latent tuberculosis infection in contagious tuberculosis (TB) contact subjects.To assess the QFT assay in recently exposed contacts of active tuberculosis patients in a French area with low TB incidence but high Bacille Calmette-Guerin coverage, and evaluate progression rates to TB disease.Methodology/Principal FindingsBetween January 2007 and December 2009, 687 contacts of culture-confirmed tuberculosis cases underwent the QFT assay, with tuberculin skin test (TST) in 473, and a 34 months mean follow-up. Of 687 contacts, 148 were QFT positive, while 526 were negative and 13 indeterminate. QFT was positive in 35% of individuals with TST ≥10 mm, 47.5% with TST ≥15 mm or phlyctenular, but in 21% of cases in which two-step TST (M0 and M3) remained negative. Conversely, QFT was negative in 69% of cases with two-step TST showing conversion from negative to positive. All indeterminate QFT were associated with TST induration <10 mm in diameter. For 29 QFT-positive subjects, no chemoprophylaxis was given due to medical contraindications. Of the remaining 119 QFT-positive contacts, 97accepted chemoprophylaxis (81.5%), and 79 (81.4%) completed the treatment. Two contacts progressed to TB disease: one subject was QFT positive and had declined chemoprophylaxis, while the other one was QFT negative. QFT positive predictive value for progression to TB was 1.96% (1/51) with a 99.8% (525/526) negative predictive value.Conclusions/SignificanceOur results confirm the safety of the QFT-based strategy for assessing the TB chemoprophylaxis indication, as only one contact developed TB disease out of 526 QFT-negative subjects.

Comparison of specificities between two interferon-gamma release assays in Japan [Short communication

We compared the specificities of two interferon-gamma release assays (IGRAs), T-SPOT®.TB (T-SPOT) and the QuantiFERON®-TB Gold In-Tube (QFT-GIT) assay, in strictly selected subjects with a low risk of tuberculosis (TB) infection in a Japanese population. Of 111 subjects who were mostly bacille Calmette-Guérin vaccinated, one was positive using both assays and 110 were negative, using international cut-off values. Although several meta-analyses report that QFT-GIT has higher specificity than T-SPOT, our study demonstrates that the specificity of both assays is equally high in a population with a truly low risk of TB infection.

Identifying predictors of interferon-γ release assay results in pediatric latent tuberculosis: a protective role of bacillus Calmette-Guerin?: a pTB-NET collaborative study.

Interferon-γ (IFN-γ) release assays are widely used to diagnose latent infection with Mycobacterium tuberculosis in adults, but their performance in children remains incompletely evaluated to date. To investigate factors influencing results of IFN-γ release assays in children using a large European data set. The Pediatric Tuberculosis Network European Trials group pooled and analyzed data from five sites across Europe comprising 1,128 children who were all investigated for latent tuberculosis infection by tuberculin skin test and at least one IFN-γ release assay. Multivariate analyses examined age, bacillus Calmette-Guérin (BCG) vaccination status, and sex as predictor variables of results. Subgroup analyses included children who were household contacts. A total of 1,093 children had a QuantiFERON-TB Gold In-Tube assay and 382 had a T-SPOT.TB IFN-γ release assay. Age was positively correlated with a positive blood result (QuantiFERON-TB Gold In-Tube: odds ratio [OR], 1.08 per year increasing age [P < 0.0001]; T-SPOT.TB: OR, 1.14 per year increasing age [P < 0.001]). A positive QuantiFERON-TB Gold In-Tube result was shown by 5.5% of children with a tuberculin skin test result less than 5 mm, by 14.8% if less than 10 mm, and by 20.2% if less than 15 mm. Prior BCG vaccination was associated with a negative IFN-γ release assay result (QuantiFERON-TB Gold In-Tube: OR, 0.41 [P < 0.001]; T-SPOT.TB: OR, 0.41 [P < 0.001]). Young age was a predictor of indeterminate IFN-γ release assay results, but indeterminate rates were low (3.6% in children < 5 yr, 1% in children > 5 yr). Our data show that BCG vaccination may be effective in protecting children against Mycobacterium tuberculosis infection. To restrict use of IFN-γ release assays to children with positive skin tests risks underestimating latent infection.

Development of a diagnostic gene expression assay for tuberculosis and its use under field conditions in African buffaloes (Syncerus caffer)

The development of diagnostic tests for tuberculosis (TB) in exotic species is constrained by host biology and the limited availability of suitable assay reagents. As such, we evaluated a gene expression assay (GEA) which is easily modified for novel species and allows for initial sample processing under field conditions. African buffaloes (Syncerus caffer) were categorized using the single comparative intradermal tuberculin test, and blood from test-positive and test-negative animals was incubated for 20h in “Nil” tubes (containing saline) and “TB Antigen” tubes (containing Mycobacterium tuberculosis complex (MTC)-specific antigens) of a commercial human TB test, the QuantiFERON®-TB Gold (In-Tube) (QFT) assay. Blood samples were then stabilized in RNAlater® and transported to the laboratory for RNA extraction. A Custom TaqMan GEA was used to calculate the relative abundance of interferon-gamma (IFN-γ) mRNA in the TB Antigen tube compared to that in the Nil tube as a marker of immune activation in response to MTC antigen recognition. The GEA results from the two buffalo groups were compared and a cutoff value of 2.85 was calculated to differentiate between animals from these groups with a sensitivity of 80% (95% C.I.: 56–94%) and a specificity of 95% (95% C.I.: 75–100%). Further optimization of this assay could provide a highly useful tool for the diagnosis of MTC infection in exotic species.

Serial interferon-gamma release assays after chemoprophylaxis in a tuberculosis outbreak cohort

Interferon-gamma release assay (IGRA) results have been suggested as a surrogate marker of treatment response in latent tuberculosis infection (LTBI). However, data have not been consistent, and most previous studies focused on participants taking isoniazid prophylaxis. The aim of this study was to elucidate the changes in the IGRA results in patients who underwent chemoprophylaxis with isoniazid and rifampicin daily for 3months. In a TB outbreak cohort, 26 asymptomatic close contacts with normal chest radiographs and positive QuantiFERON-TB Gold In-Tube assay (QFT-GIT) results were recruited. These patients were treated with isoniazid and rifampicin daily for 3months. The QFT-GIT was repeated at 3 and 6months following treatment initiation. Compared with the initial QFT-GIT results (3.59±3.39IU/mL), the interferon-gamma (IFN-γ) levels had decreased significantly at 6months (0.84±1.14IU/mL; P=0.005), but not at 3months (3.58±3.64IU/mL; P=0.98). Reversions occurred in seven (26.9%) patients at 3months and in an additional two participants at 6months; a total of nine participants (34.6%) had reversions. Recent conversion was associated with reversion of the test results (odds ratio26.3, 95% confidence interval3.04-226.6). Chemoprophylaxis with isoniazid and rifampicin generally decreased IFN-γ levels among tuberculosis contacts. However, only a small portion of participants achieved reversion.

Role of the QuantiFERON®-TB Gold In-Tube assay in screening new immigrants for tuberculosis infection

This study aimed to estimate the risk of progression to active tuberculosis (TB) within 2 yrs after entry in newly arriving immigrants who were screened with the QuantiFERON®-TB Gold In-Tube assay (QFT-GIT; Cellestis, Carnegie, Australia).In a case–base design, we determined the prevalence QFT-GIT-positive subjects among a representative sample of immigrants aged ≥18 yrs who arrived between April 2009 and March 2011 (the base cohort). Active TB patients (cases) within 2 yrs post-arrival in 2005, 2006 or 2007 were extracted from the Netherlands Tuberculosis Register. The risk of progression to active TB was estimated using Bayesian analyses to adjust for the sensitivity of QFT-GIT.Among the base cohort, 20% of 1,468 immigrants were QFT-GIT positive. Stratified by TB incidence in the person's country of origin as low (<100 cases per 100,000 population), intermediate (100–199 cases per 100,000) or high (≥200 cases per 100,000), the risk of progression to active TB per 100,000 arriving immigrants if QFT-GIT positive (95% credibility interval) was 456 (95% CI 307–589), 590 (397–762) and 386 (259–499), respectively, compared with 18 (0–46), 38 (0–97) and 28 (0–71) if QFT-GIT negative.Screening newly arriving immigrants with QFT-GIT contributes to detecting those at high risk of subsequent TB reactivation within 2 yrs after entry, which offers opportunities for prevention by targeted interventions.

QuantiFERON®-TB Gold In-Tube assay vs. tuberculin skin test in Indonesian children living with a tuberculosis case

The tuberculin skin test (TST) has limitations in diagnosing latent tuberculosis (TB) infection (LTBI). Interferon-gamma release assays may improve diagnostic accuracy. We compared QuantiFERON®-TB Gold In-Tube (QFT-GIT) and TST in Indonesian children. Children aged from 6 months to 9 years exposed to a TB case at household and neighbourhood levels were recruited. The children underwent QFT-GIT and TST. Test responsiveness was assessed according to an exposure gradient. A total of 299 household-exposed and 72 neighbourhood-exposed children were analysed. Overall, respectively 46% and 41% were positive using QFT-GIT and the TST. Test positivity increased with exposure (QFT-GIT P value for trend <0.001, and TST P < 0.001); however, only QFT-GIT responded significantly to a 'within-household' gradient. The TST was less likely to be positive than the QFT-GIT in neighbourhood-exposed children (P = 0.05). BCG-vaccinated children were less likely to be QFT-GIT-positive, while older children were more likely to be QFT-GIT-positive. Both tests had increasing positivity with increasing smear grade. QFT-GIT performed similarly to the TST in Indonesian children living with an infectious TB case. Test accuracy was not compromised by young age or BCG vaccination. Our findings suggest that QFT-GIT offers little advantage over the TST in this population. High rates of LTBI diagnosed in household-exposed children by both tests support preventive therapy.

Interferon gamma and interferon gamma inducible protein-10 in detecting tuberculosis infection

This study aimed to compare the levels of TB-antigen specific Interferon gamma (IFN-γ) and IFN-γ inducible protein (IP)-10 in culture of whole blood samples from healthy controls (HC) and healthy household contacts (HHC). A total of 386 study subjects, which included 186 HC and 200 HHC, were recruited. QuantiFERON-TB Gold in-tube (QFT-IT) assay was employed to measure IFN-γ levels. IP-10 levels were measured in the supernatants collected from QFT-IT tubes. Tuberculin skin test was also performed. The levels of TB antigen specific IFN-γ and IP-10 were significantly higher in HHC compared to HC. There was no significant difference observed between positivity of QFT-IT and IP-10 in HC and HHC. The positivity of TST was significantly lower in subjects <17 year, when compared to IP-10 (p<0.005). The reduced cut-off point 0.22IU/ml significantly increased the positivity of QFT-IT among children with high risk for latent TB infection (LTBI). Measurement of TB antigen specific IFN-γ and IP-10 can be potential markers for the detection of LTBI.

Antituberculosis IgG Antibodies as a Marker of Active Mycobacterium tuberculosis Disease

Anti-Mycobacterium tuberculosis IgG antibodies may aid in the diagnosis of active M. tuberculosis disease. We studied whether anti-M. tuberculosis IgG antibodies are elevated in active M. tuberculosis disease and assessed factors contributing to false-positive and -negative results. A retrospective study of 2,150 individuals tested by the QuantiFERON-TB Gold In-Tube (QFT-GIT) assay was conducted at the University of Utah, ARUP Laboratories, November 2008 to December 2010. All samples were tested with the InBios Active TbDetect antituberculosis (anti-TB) IgG antibody assay. Of 1,044 patients with a positive QFT-GIT, 59 (5.7%) were positive for M. tuberculosis antibodies. Fourteen of 1,106 (1.3%) with a negative or indeterminate QFT-GIT were positive for M. tuberculosis antibodies. M. tuberculosis antibody tests were positive in 61.5% with confirmed active M. tuberculosis disease and other mycobacterial infections. Over half of the false-negative M. tuberculosis antibody tests occurred in patients ≥ 90 years of age. False positives were seen in 12.9% of autoimmune patients. The odds ratio of being positive by the QFT-GIT and the InBios TB IgG assay increased with confirmed M. tuberculosis disease or highly suspected M. tuberculosis disease and was 86.7 (95% confidence interval [CI], 34.4 to 218.5) in these two groups compared to patients negative by both tests. Although anti-M. tuberculosis antibodies can be detected in patients with active M. tuberculosis disease, caution should be used with patients where immunoglobulin levels may be decreased or patients with autoantibodies.