Guidelines for using the QuantiFERON-TB test for diagnosing latent Mycobacterium tuberculosis infection. Centers for Disease Control and Prevention.

Until 2001, the only test used to diagnose latent tuberculosis infection (LTBI) was the tuberculin skin test (TST). However, in 2001, a new test (QuantiFERON-TB or QFT; manufactured by Cellestis Limited, Carnegie, Victoria, Australia) that measures the release of interferon-gamma in whole blood in response to stimulation by purified protein derivative was approved by the Food and Drug Administration. This statement provides interim recommendations for using and interpreting QFT. As with TST, interpretation and indicated applications of QFT differ for persons according to their risk for LTBI and for developing tuberculosis (TB). This report provides guidance for public health officials, health-care providers, and laboratorians with responsibility for TB control activities in the United States in their efforts to incorporate QFT testing for detecting and treating LTBI. Regardless of the test used to identify LTBI, testing should be primarily targeted at diagnosing infected patients who will benefit from treatment.     

Performance of an interferon-gamma release assay for diagnosing latent tuberculosis infection in children

Newly developed interferon-gamma release assays have become commercially available to detect tuberculosis (TB) infection in adults. However, little is known about their performance in children. We compared test results between the QuantiFERON-TB Gold test (QFT) and tuberculin skin test (TST) in young children living with pulmonary TB patients in Cambodia. Of 195 children tested with both QFT and TST, the TST-positive rate of 24% was significantly higher than the QFT-positive rate of 17%. The agreement between the test results was considerable (kappa-coefficient 0.63). Positive rates increased from 6% to 32% for QFT and from 15% to 43% for TST, according to the sputum smear grades of the index cases. The presence of Bacille Calmette-Guérin (BCG) scars did not significantly affect the results of TST or QFT in a logistic regression analysis. In conclusion, QFT can be a substitute for TST in detecting latent TB infection in childhood contacts aged 相似文献   

Detecting Mycobacterium tuberculosis Infection in Children Migrating to Australia

In 2015, Australia updated premigration screening for tuberculosis (TB) disease in children 2–10 years of age to include testing for infection with Mycobacterium tuberculosis and enable detection of latent TB infection (LTBI). We analyzed TB screening results in children <15 years of age during November 2015–June 2017. We found 45,060 child applicants were tested with interferon-gamma release assay (IGRA) (57.7% of tests) or tuberculin skin test (TST) (42.3% of tests). A total of 21 cases of TB were diagnosed: 4 without IGRA or TST, 10 with positive IGRA or TST, and 7 with negative results. LTBI was detected in 3.3% (1,473/44,709) of children, for 30 applicants screened per LTBI case detected. LTBI-associated factors included increasing age, TB contact, origin from a higher TB prevalence region, and testing by TST. Detection of TB and LTBI benefit children, but the updated screening program’s effect on TB in Australia is likely to be limited.     

Evaluation of the interferon-γ release assay in healthcare workers

Objectives An in vitro test for the diagnosis of latent TB-infection (LTBI) is now available that has the potential to replace the tuberculin skin test (TST). The new test measures the cell-mediated immune response to TB antigens. Little experience is currently available on the performance of the IGRA when testing HCW for LTBI. Therefore the aim of the study was to compare the IGRA with the TST in testing HCW for LTBI. Methods The medical staffs of three hospitals were simultaneously tested with TST (RT23) and IGRA (QFT). The study comprises 261 HCW, all exposed to active TB-patients. Information on gender, age, workplace, BCG vaccination and history of both TB and TST were collected using a standardised questionnaire. Results The TST was positive in 24.1% and the IGRA in 9.6% of the participants. Agreement between the tests was low in HCW with a BCG-vaccination. A history of an earlier TST was a risk factor for a positive TST but not for a positive IGRA. Out of 48 results positive in the TST but negative in the IGRA 97.8% might be explained by BCG vaccination or an earlier TST. A positive association between age and LTBI was observed for the IGRA but not for the TST results. Out of 25 positive results in the IGRA only 60% were recognized by the TST, too. The HCW with a positive IGRA and a negative TST had the same age (mean 49.1) as the HCW positive in both tests (mean 50.9), which was higher than the age of those negative in both tests (mean 38.8). Conclusions The data indicate that the IGRA should replace the TST in serial testing of HCW in high income, low incidence countries. The recommendations to use the IGRA in order to verify a positive TST only should be reconsidered.     

北京市昌平区某高校大学新生结核潜伏感染调查

目的 调查大学新生结核潜伏感染情况,以便采取预防性措施。 方法 2010年10月随机纳入北京市昌平区某高校入学新生TST≥10 mm的健康受试者420例,应用ELISPOT检测经抗原刺激后分泌IFN-γ的效应T淋巴细胞(即斑点形成细胞,SFCs)数量,并对ELISPOT阳性者进行为期3年的结核感染发病情况监测。 结果 ELISPOT检测LTBI总的阳性率为41.2%,在BCG接种(阳性率41.5%)和未接种(阳性率40.0%)中差异无统计学意义(χ²=0.064, P=0.447),在TST直径10~14、15~19和≥20 mm组间(37.6%、45.4%和64.3%)差异有统计学意义(χ²=8.408, P=0.015),173例未治疗的 ELISPOT+/TST+者经3年的ATB监测,发病率为0。 结论 北京市昌平区某高校大学新生LTBI比率高,但仅以ELISPOT和TST双阳性者为预防性治疗指标,尚不足够。     

Prevalence and associated risk factors of latent tuberculosis infection among undergraduate and postgraduate dental students: A retrospective study

To estimate the prevalence of latent tuberculosis (TB) infection (LTBI) in Italian dental students exposed to the same occupational risks as dental health care personnel and to evaluate potential risk factors, a cross-sectional study was conducted on undergraduate and postgraduate students. After clinical evaluation, students were given a tuberculin skin test; in those found positive, an interferon-γ release assay (IGRA) was conducted. Of the 281 students enrolled, 10 were only TST positive; 8 were TST or/and IGRA positive. We found that participants testing positive at TST and/or IGRA, a group in which the risk of false LTBI positives is minimal, were older and had been studying longer. Although the prevalence of LTBI among dental students in our study was low, a risk of acquiring a work-related infection exists even in a country with a low incidence of TB. Thus, dental students should be screened to catch LTBI early on.     

Treatment for latent TB in correctional facilities: a challenge for TB elimination

BACKGROUND: To eliminate tuberculosis (TB) in the United States, more information is needed on how to gain access to difficult-to-reach, high-risk populations to evaluate people who would benefit from treatment for latent TB infection (LTBI). METHODS: A field study was conducted of people at risk for co-infection with TB and the human immunodeficiency virus (HIV) and to demonstrate that treating LTBI in inmates is feasible. Inmates were tested for LTBI using the Mantoux tuberculin skin test (TST). Outcomes measured were skin test results and the start and completion of treatment for LTBI. RESULTS: In 49 correctional facilities in 12 states, 198102 inmates had a skin test read. The mean skin test positivity rate among inmates was 17.0%. Of those who had a known HIV test result, 14.5% tested HIV positive. Inmates with a positive TST were 4.2 times more likely than those with a negative TST to be HIV infected (95% confidence interval [CI]=3.9-4.4). Therapy for LTBI was completed in 55.9% of patients started on treatment. Patients who were HIV positive and started on a 12-month treatment regimen were less likely than HIV-negative patients (40.0% vs 68.1%, respectively) to complete treatment (odds ratio [OR]=0.24, 95% CI=0.20-0.28). Patients treated in jails were less likely than those treated in prisons (33.6% vs 57.7%, respectively) to complete treatment (OR=0.29, 95% CI=0.26-0.32). CONCLUSIONS: Correctional facilities offer a venue for identifying and treating high-risk individuals for LTBI. However, completing treatment is more problematic in jails than in prisons.     

中国东部地区结核菌素试验诊断结核病感染临界值的确定：基于人群的现况调查

目的 确定结核菌素试验的临界值来降低其诊断结核病潜伏性感染的假阳性。方法 测量受试者的FPG值,同时对受试者做结核菌素试验和QuantiFERON-TB（QFT）Gold In-Tube检测。以QFT为金标准,确定结核菌素试验（TST）试验的临界值。结果 共有5 405名参与者,其中1 104名（20.4%）QFT阳性。在5 405例患者中,PPD硬结直径为10.25 mm时诊断价值最高,其灵敏度为0.731,特异度为0.727。将受试者分为正常人、有糖尿病史患者、新确诊糖尿病患者,硬结直径分别在11.25 mm、10.25 mm和11.25 mm时诊断价值最高,其灵敏度和特异度分别为0.701、0.837、0.824和0.805、0.821、0.778。结论 本研究证实,以10~12 mm作为结核病潜伏性感染诊断的临界值可以大大提高结核菌素试验的特异性。     

Challenges to tuberculin screening and follow-up in an urban Aboriginal sample in Montreal, Canada

We sought to describe the prevalence and predictors of tuberculin skin test (TST) reactors in a high-risk sample of urban Aboriginal people, and to evaluate adherence to medical evaluation and latent tuberculosis infection (LTBI) treatment among those with TST reactivity. Of the 164 participants tested, 86% returned for TST reading. Positive TST reactions (>or=10 mm) were observed in 17.7% (25/141, 95% CI 11.4-24.0) of participants, and were associated with older age (OR per 10 year increase 1.8, 95% CI 1.2-2.7) and Inuit Aboriginal group (OR 2.8, 95% CI 1.1-7.3). Only four participants presented for evaluation, of whom one initiated and none completed LTBI treatment. Tuberculin screening in this population can be an effective strategy for identifying TST reactive individuals; however, screening efforts will have minimal impact without additional efforts in this high-risk group.     

In-hospital contact investigation among health care workers after exposure to pulmonary tuberculosis in an intermediate tuberculosis prevalence area: A prospective study

We carried out in-hospital contact investigations of patients with pulmonary tuberculosis and analyzed the prevalence of latent tuberculosis infection (LTBI) among health care workers (HCWs) after TB exposure. A prospective study was conducted of 872 HCWs who were exposed to 55 index cases diagnosed with active pulmonary TB. HCWs after TB exposure were evaluated both TST and chest X-ray at the time of enrollment and 12 weeks after exposure; 625 HCWs (71.6%) underwent both initial assessments; 41 HCWs (6.6%) had a positive TST result. After 12 weeks, 71.1% of HCWs with initial negative TST (n = 415) underwent a second assessment. Ten HCWs had TST conversion. One HCW (0.2%) developed active pulmonary TB. In multivariable analysis, age over 30 years was associated with TST conversion (p = .02). Point prevalence of latent TB was 6.6%, and incidence of LTBI was estimated as 2.4 per 100 HCWs. Strict infection control measures should be emphasized in intermediate TB-burden, BCG-vaccinated countries, especially in HCWs with high risk for TB exposure.     

Latent Tuberculosis Infection Among Immigrant and Refugee Children Arriving in the United States: 2010

Immigrants and refugees age 2–14 years entering the United States from countries with estimated tuberculosis (TB) incidence rate ≥20 per 100,000 population are screened for TB. Children with TB disease are treated before US arrival. Children with positive tuberculin skin tests (TST), but negative TB evaluation during their pre-immigration examination, are classified with latent TB infection (LTBI) and are recommended for re-evaluation post-arrival. We examined post-immigration TB evaluation and therapy for children arriving with LTBI. We reviewed medical exam data from immigrant children with medical conditions and all refugee children arriving during 2010. Medical examination data were available for 67,334 children. Of these, 8231 (12 %) had LTBI pre-immigration; 5749 (70 %) were re-evaluated for TB post-immigration, and 64 % were retested by TST or IGRA. The pre-immigration LTBI diagnosis was changed for 38 % when retested by TST and for 71 % retested by IGRA. Estimated LTBI therapy initiation and completion rates were 68 and 12 %. In this population, testing with IGRA may limit the number of children targeted for therapy. Increased pre-immigration TB screening with post-immigration follow-up evaluation leading to completion of LTBI therapy should be encouraged to prevent TB reactivation.     

Impact of Routine Quantiferon Testing on Latent Tuberculosis Diagnosis and Treatment in Refugees in Multnomah County,Oregon, November 2009–October 2012

Interferon-gamma release assays have potentially been transformative to screening programs focused on latent tuberculosis infection (LTBI) in foreign-born persons. We sought to add to this assessment by presenting the impact of a well-established refugee screening and treatment program switching from skin testing to Quantiferon^®-TB Gold (QFT). We completed a retrospective cohort of refugees screened for tuberculosis between November 1, 2009–April 30, 2011 (pre-QFT) and May 1, 2011–October 31, 2012 (post-QFT). Among 2244 refugees screened that met the inclusion criteria, there was a significant difference in the proportion of refugees diagnosed with LTBI between the two time periods (p = <0.0001). In multivariate analysis, refugees tested with QFT had a greater odds of treatment initiation (adjusted odds ratio 1.53; 95 % CI 1.02–2.29, p = 0.040). However, test type had no impact on treatment completion (odds ratio 0.88; 95 % CI 0.57–1.36, p = 0.560). Although we demonstrated increased efficiency in LTBI diagnosis in this group, treatment completion rates indicate other barriers to treatment that must be addressed.     

Feasibility of latent tuberculosis infection diagnosis by interferon-γ release assay remote from testing facilities

Although the tuberculin skin test (TST) has been the mainstay of the diagnosis of latent tuberculosis infection (LTBI) for many decades, interferon-gamma release assays (IGRAs) are gaining acceptance and are more specific for this diagnosis. The characteristics of one such IGRA, the QuantiFERON-TB Gold Whole Blood In-Tube, make it feasible for use in a remote setting. This study performed 62 IGRAs with this test on individuals testing positive by TST, in a clinical setting over 3,000 km from the testing laboratory. Of these, 42 patients (68%) recorded negative results, 19 (31%) were positive, with only 1 result (2%) indeterminate. Negative, and therefore discordant in this study, test results were more common in those known to have been previously vaccinated with bacille Calmette-Guérin. These results are consistent with other reports, indicating that this approach to testing is logistically feasible, and has the potential to complement LTBI screening to assist tuberculosis control programs in settings remote from the testing laboratory.     

Utility of QuantiFERON TB-2G for tuberculosis contact investigations in public health services

OBJECTIVE: The objective of the present study was to examine the utility of QuantiFERON TB-2G (QFT) in tuberculosis contact investigations performed by a public health center. METHODS: Adachi City Public Health Center, Tokyo, started using QFT in its laboratory service in June, 2005. The results of QFT, as well as tuberculin skin tests (TSTs) performed in tuberculosis contact investigations in the 10 month period since then were here analyzed. QFT was carried out for 67 contacts two months after their last contact with the index case. TST was given simultaneously. RESULTS: Of the total of 67 contacts investigated during the period, 9 were positive for QFT, 5 were doubtful positive, and the remaining 53 were negative. Among 48 subjects tested with TST, 22 had strong reactions with erythema > or = 30 mm, out of which 4 were positive for QFT. In addition, there were 5 QFT-positives among the remaining 26 with weak tuberculin reactions. These 9 subjects with positive QFT were indicated for chemoprophylaxis. CONCLUSIONS: Adachi City Public Health Center is pioneering the application of new technology for detection of latent tuberculosis infection in contact investigations of the inhabitants. As expected from trial findings, QFT was shown to be a useful tool in a practical setting for the purpose of detecting TB infection, with greater accuracy than with TST, independent of the history of BCG vaccination. This approach can help avoid both over-diagnosis and under-diagnosis.     

Prevalence of latent tuberculosis infection in German radiologists

Healthcare workers have an increased risk of tuberculosis infection compared with the general population. There have been few attempts to quantify the prevalence of latent tuberculosis infection amongst German healthcare workers, due to inadequacy of the current tuberculin skin test (TST). Therefore, it was our aim to investigate the prevalence of latent tuberculosis in this cohort using a tuberculosis-specific ELISpot (T-SPOT.TB) test and to compare the performance of this test to that of the TST. Ninety-five healthy participants working in departments of radiology were examined by ELISpot, lymphocyte transformation test and TST. For cellular in-vitro tests, tuberculosis-specific peptides and purified protein derivate (PPD) were used as antigens. These tests were combined with a questionnaire on prior tuberculosis exposure. Out of 95 healthcare workers, only one (1%) was defined as positive by T-SPOT.TB, 92 (97%) by PPD-ELISpot, 78 (82%) by PPD-lymphocyte transformation test and 32 (34%) by TST. Multivariate analysis showed that the TST was significantly affected (P<0.0001 and P=0.001, respectively) by foreign birth and prior skin testing. The T-SPOT.TB test results were independent of foreign birth, prior skin testing and prior vaccination against tuberculosis. In contrast to the TST, T-SPOT.TB appears to be an accurate and useful tool to track tuberculosis infection in this at-risk group. With only one of 95 participants having acquired latent tuberculosis, these preliminary results argue for a low incidence of latent tuberculosis in German radiologists.     

High rate of negative results of tuberculin and QuantiFERON tests among individuals with a history of positive skin test results.

OBJECTIVES: To evaluate individuals at high risk for tuberculosis exposure who had a history of a positive tuberculin skin test (TST) result in order to determine the prevalence of unsuspected negative TST results. To confirm these findings with the QuantiFERON-TB test (QFT), an in vitro whole-blood assay that measures tuberculin-induced secretion of interferon-gamma. METHODS: This survey was conducted from November 2001 through December 2003 at 3 sites where TST screening is regularly done. Detailed histories and reviews of medical records were performed. TSTs were placed and read by 2 experienced healthcare workers, and blood was drawn for QFT. Any subject with a negative result of an initial TST during the study (induration diameter, <10 mm) underwent a second TST and a second QFT. The TST-negative group comprised individuals for whom both TSTs had an induration diameter of <10 mm. The confirmed-negative group comprised individuals for whom both TSTs yielded no detectable induration and results of both QFTs were negative. RESULTS: A total of 67 immunocompetent subjects with positive results of a previous TST were enrolled in the study. Of 56 subjects who completed the TST protocol, 25 (44.6%; 95% confidence interval [CI], 31.6%-57.6%) were TST negative (P<.001). Of 31 subjects who completed the TST protocol and the QFT protocol, 8 (25.8%; 95% CI, 10.4%-41.2%) were confirmed negative (P<.005). CONCLUSIONS: A significant proportion of subjects with positive results of a previous TST were TST negative in this study, and a subset of these were confirmed negative. These individuals' TST status may have reverted or may never have been positive. It will be important in future studies to determine whether such individuals lack immunity to tuberculosis and whether they should be considered for reentry into tuberculosis screening programs.     

Screening for tuberculosis infection using whole-blood interferon-gamma and Mantoux testing among Japanese healthcare workers.

OBJECTIVE: To examine the hypothesis that results of the QuantiFERON-TB Gold assay (QFT-G), a whole-blood test for detection of tuberculosis infection, are more significantly related to known risk factors for tuberculosis infection in healthcare workers (HCWs) who have received bacille Calmette-Guerin vaccine than are results of the Mantoux tuberculin skin test (TST). DESIGN: All HCWs (approximately 510) from a 370-bed general hospital in Tokyo where patients with and patients without tuberculosis are treated were invited to participate in the study. All study participants completed a questionnaire about their Mycobacterium tuberculosis infection risk factors as HCWs at the general hospital. They were then tested for LTBI by means of the QFT-G, followed by the TST. Statistical analyses were performed to compare results of each test with M. tuberculosis infection risk factors (age, length of employment in the healthcare industry, history of working with tuberculosis-positive patients in a tuberculosis ward or in the outpatient department of the hospital's tuberculosis clinic for more than 1 year, chest radiograph evidence of healed tuberculosis, history of performing bronchoscope procedures, and job classification), and for TST-positive HCWs, to compare the QFT-G result with the TST induration diameter. RESULTS: A total of 332 HCWs (95% of whom had been vaccinated with BCG) participated in the study, and 33 had positive QFT-G results, suggesting a prevalence of LTBI of 9.9%. Of 304 HCWs who underwent TST, 283 (93.1%) had an induration diameter of 10 mm or more. Multiple logistic regression analysis revealed that positive QFT-G results were significantly associated with age and with a history of working in a tuberculosis ward or an outpatient department of a tuberculosis clinic. TST results were not correlated with any of the tuberculosis infection risk factors we evaluated. CONCLUSIONS: Positive QFT-G results were closely associated with the presence of risk factors for LTBI in a hospital setting, suggesting that the QFT-G can detect LTBI in a population composed predominantly of BCG vaccinees. Because most HCWs worldwide have been vaccinated with BCG, the QFT-G offers a significant improvement over the TST in tuberculosis screening programs and minimizes unwarranted use of tuberculosis prophylaxis.     

Comparing the performance of QuantiFERON-TB Gold and Mantoux test in detecting latent tuberculosis infection among Iranian health care workers

Objectives  

The risk of transmission of Mycobacterium tuberculosis from patients with tuberculosis to health care workers (HCWs) has been well documented but little is known about the prevalence of latent tuberculosis infection (LTBI) in Iranian HCWs. The aim of this study was to determine the prevalence of LTBI among HCWs by using IFNgamma-release assay and compare the results with those of tuberculin skin test (TST).     

High abundances of neurotrophin 3 in atopic dermatitis mast cell

Background  

Little is known about the prevalence of latent tuberculosis infections (LTBI) in health care workers (HCW) in low-incidence countries especially in hospitals for pulmonary diseases. With Interferon-gamma release assays (IGRA), a new method for diagnosis of LTBI is available which is more specific than the tuberculin skin test (TST).