Diagnosis Of Latent Tuberculosis Infection Research Articles

Interferon Gamma Release Assays in Patients with Respiratory Isolates of Non-Tuberculous Mycobacteria - a Preliminary Study.

Interferon gamma releasing assays (IGRAs) are extensively used in the diagnosis of latent tuberculosis infections. Comparing to tuberculin skin test (TST) they lack false positive results in the populations vaccinated with BCG, and in most non-tuberculous mycobacteria (NTM) infections. Nevertheless, Mycobacterium kansasii, Mycobacterium marinum, and Mycobacterium szulgai may induce positive IGRAs due to RD1 homology with Mycobacterium tuberculosis. The aim of the study was to investigate the possible influence of NTM respiratory isolates on the results of IGRAs. 39 patients (23 females and 16 males) of median age 61 years, with negative medical history concerning tuberculosis, entered the study. Identification of NTM was performed using the niacin test and molecular method GenoType CM test (Hain Lifescience). QFT-Plus was performed in 17 patients, T-SPOT-Tb – in 23 patients. Chest X-rays and a high-resolution computed tomography of the chest have been reviewed by the experienced radiologist blinded to the results of IGRAs, in search of past tuberculosis signs. Positive IGRAs results were obtained in three out of 39 patients (8%): 22% of patients with M. kansasii isolates and 18% of patients with radiological signs on HRCT that might be suggestive of past tuberculosis. Positive IGRAs correlated with radiological signs suggestive of past tuberculosis (r = 0.32, p = 0.04), and on the borderline with isolation of M. kansasii (r = 0.29, p = 0.06). These findings may suggest that a positive IGRAs result, in our material, could depend mostly on asymptomatic past Tb infection. The cross-reactivity of M. kansasii isolates with IGRAs was less probable; nevertheless, it requires further investigations.

ИММУНОДИАГНОСТИКА ТУБЕРКУЛЕЗА: ДЕСЯТИЛЕТНИЙ ОПЫТ ПРИМЕНЕНИЯ ИММУНОЛОГИЧЕСКИХ ТЕСТОВ В РОССИИ

The introduction of a new generation of immunological tests based on in vitro or in vivo reactions using specific ЕSAT-6 and CFP-10 peptides allowed changing the understanding of the diagnosis of latent tuberculosis infection, as well as improving the diagnosis of tuberculosis in pediatric and adult practice. The article presents the analysis of the Russian studies conducted over the past ten years aimed to investigate the informativeness of a skin test with tuberculosis recombinant allergen. High diagnostic significance of the skin test, comparable to the internationally recognized IGRA-tests has been proved. Today, the test with TRA in the form of locally manufactured Diaskintest has been introduced inRussianot only to the practice of TB units, but also in the practice of pediatricians, pulmonologists and infectious disease specialists.

Validation and Clinical Application of Interferon-Gamma Release Assay for Diagnosis of Latent Tuberculosis Infection in Children.

Background:India has the highest tuberculosis (TB) burden, accounting for one-fifth of the global incidence and two-third of the cases in Southeast Asia with an estimated 1.9 million new cases every year. Identifying and treating latent TB infection (LTBI) can reduce the risk of development of active disease by up to 90%, thereby decreasing a major burden to the prevalence of the disease, and thus reducing potential sources in future.Aim:Early diagnosis of LTBI by tuberculin skin test (TST) and a newer interferon-gamma release assay (IGRA).Materials and Methods:Seventy-seven clinically asymptomatic household contacts (≤18 years) of confirmed pulmonary TB patients were enrolled to compare the performance of TST and IGRA to diagnose LTBI. At baseline, all participants underwent testing for IGRA and TST.Results:TST showed positivity of 22%, while IGRA demonstrated positivity of 40% in the diagnosis of latent TB. Kappa value at 95% confidence interval was 0.4753, indicates a moderate agreement between the two tests. This indicates that IGRA is a better predictor of latent TB. Maximum positive percentage was in the age group of 16–18 years in both the tests followed by 1–5 years.Aim:Early diagnosis of LTBI by tuberculin skin test (TST) and a newer interferon-gamma release assay (IGRA).

Factors Influencing the Diagnosis and Treatment of Latent Tuberculosis among Contacts in Congregated Settings in Korea.

BackgroundThis study aimed to compare the indicators (the rates of diagnosis, need for treatment, treatment initiation, and treatment completion) of management of latent tuberculosis infection (LTBI) in contacts and to identify the impact of active tuberculosis (TB) index case characteristics on the exposed population in congregated settings, such as schools, workplaces, and medical institutes.MethodsThe data of 8,648 clusters in the TB epidemiological investigation database between 2013 and 2016 were extracted and analyzed to evaluate the indicators and perform multilevel logistic regression (MLR) analyses to identify the factors affecting each indicator.ResultsThe rates of total LTBI diagnosis, need for treatment, treatment initiation, and treatment completion were 15.2%, 10.2%, 69.4%, and 76.6%, respectively. After adjusting for other factors on MLR, the probability of diagnosis and need for treatment of latent TB in contacts was higher in most types of facilities than in schools. Conversely, treatment completion rates in these facilities were lower. Notably, the correctional institutions showed the highest odds ratio (OR) relative to school for LTBI diagnosis (OR, 6.37) and need for treatment (OR, 4.49) and the lowest OR for treatment completion (OR, 0.10).ConclusionThis study provided evidence for the implementation of latent TB control policies in congregated settings.

Selection of Health Care Workers for Screening for Latent Tuberculosis Infection

Introduction: The rate of latent tuberculosis infections (LTBIs) in health care workers (HCWs) is higher than that in non-HCWs. We studied to investigate the prevalence and risk factors of LTBIs and the acceptance rate for treatment of LTBI among HCWs in South Korea, a country with an intermediate tuberculosis (TB) burden. Methodology: LTBI screening was conducted for HCWs at a tertiary and a secondary hospital from April 2017 to August 2017. This was a retrospective study included all HCWs who underwent LTBI examination. HCWs were classified by the degree of risk into four groups, based on two factors: possibility of exposure to TB, and impact on patients at the time of TB onset in the HCWs. The interferon-gamma release assay was used for the diagnosis of LTBI. Results: A total of 1326 HCWs were included; they comprised 801 HCWs from a tertiary hospital and 525 from a secondary hospital. A total of 235 (17.7%) HCWs were diagnosed with LTBIs. According to risk classification, there was no significant difference (P = 0.24). In multivariate analysis, age was the only independent risk factor (P < 0.001). The acceptance rate for LTBI treatment was 60.43%, and there were no associated factors in multivariate analysis. Conclusions: HCWs did not show any significant difference in the rate of LTBI by the degree of risk, and age was the independent risk factor. LTBI screening should be conducted for all HCWs regardless of risk classification.

Precision immunoprofiling to reveal diagnostic signatures for latent tuberculosis infection and reactivation risk stratification.

Latent tuberculosis infection (LTBI) is estimated in nearly one quarter of the world's population, and of those immunocompetent and infected ~10% will proceed to active tuberculosis (TB). Current diagnostics cannot definitively identify LTBI and provide no insight into reactivation risk, thereby defining an unmet diagnostic challenge of incredible global significance. We introduce a new machine-learning-driven approach to LTBI diagnostics that leverages a high throughput, multiplexed cytokine detection technology and powerful bioinformatics to reveal multi-marker signatures for LTBI diagnosis and risk stratification. This approach is enabled through an individualized normalization procedure that allows disease-relevant biomarker signatures to be revealed despite heterogeneity in basal immune response. Specifically, cytokines secreted from antigen-challenged peripheral blood mononuclear cells were detected using silicon photonic sensor arrays and multidimensional data correlation of individually-normalized immune responses revealed signatures important for LTBI status. These results demonstrate a powerful combination of multiplexed biomarker detection technologies, precision immune normalization, and feature selection algorithms that revealed positively correlated multi-biomarker signatures for LTBI status and reactivation risk stratification from a relatively simple blood-based assay.

Infections in Healthcare Workers in Germany-22-Year Time Trends.

Health workers (HWs) run an increased risk of infection. The standardised data set of an accident insurer was used to analyse the time trends of infection-related claims and confirmed occupational diseases (ODs) in HWs. The numbers of claims and confirmed claims for different infections were analysed for the years 1996 to 2017. The rate of claims and confirmed ODs were calculated per 100,000 full-time workers. The number of claims was relatively stable over time. However, the rate per 100,000 full-time workers decreased from 25.2 to 15.4. The decrease was most pronounced for hepatitis B and hepatitis C infections, which were the most frequent infections for which claims were made at the start of the period. In 2017, tuberculosis (TB)-related claims were more frequent than those related to blood-borne virus infections. However, the growing number of TB claims does not reflect an increased infection risk, but rather improved methods for the diagnosis of latent TB infection (LTBI). Measures to prevent blood-borne virus infections in HWs were successful in the last 22 years, but attention should be paid to newly emerging infections.

PPE17 (Rv1168c) protein of Mycobacterium tuberculosis detects individuals with latent TB infection.

Latent tuberculosis infection (LTBI) is a clinically distinct category of Mycobacterium tuberculosis (Mtb) infection that needs to be diagnosed at the initial stage. We have reported earlier that one of the Mtb proline-proline-glutamic acid (PPE) proteins, PPE17 (Rv1168c) is associated with stronger B-cell and T-cell responses and could be used to diagnose different clinical categories of active TB patients with higher specificity and sensitivity than PPD and ESAT-6. Based on these observations we further tested the potential of PPE17 for the diagnosis of LTBI. We tested 198 sera samples collected from LTBI individuals (n = 61), QFT-negative (n = 58) and active TB patients (n = 79). Individuals were defined as LTBI by QuantiFERON-TB Gold In-Tube test (QFT–GIT) positive results, while active TB patients were confirmed based on the guidelines of the Revised National TB Control Programme of India. The antibody responses against PPE17, ESAT-6:CFP-10 and PPD were compared in these subjects by enzyme-linked immunosorbent assay. We observed that LTBI individuals show a higher sero-reactivity to PPE17 as compared to currently used latent TB diagnostic antigens like ESAT-6, CFP-10 and PPD. The LTBI and active TB patients display almost similar sensitivity. Interestingly, PPE17 could discriminate LTBI positive subjects from the QFT-negative subjects (P < 0.001). Our study hints that PPE17 may be used as a novel serodiagnostic marker to screen the latently infected subjects and may also be used as a complimentary tool to the QFT–GIT.

789. Comparison of Interferon-γ Release Assays (IGRAs) for Diagnosis of Latent or Active Tuberculosis in Cancer Patients

BackgroundPatients with certain types of cancer are at increased risk for progression from latent tuberculosis infection (LTBI) to active tuberculosis (ATB) because of immunosuppression. The purpose of this study was to compare the utility of the two commonly used IGRAs, QuantiFERON-TB Gold® (QFT) and T-spot.TB® (T-spot.TB), for diagnosis of LTBI or ATB in cancer patients.MethodsWe identified patients who had an initial IGRA during 2013 and 2014 at our institution. Along with demographic information, collected clinical data included type of underlying cancer or other condition, reason for testing, diagnosis of ATB following testing, and absolute lymphocyte count (ALC) at the time of testing. IGRA results (positive, negative, borderline, or indeterminate/invalid) were compared between patients who underwent testing with either QFT or T-spot.TB.ResultsA total of 356 patients had 411 QFT tests done, while 737 patients had 853 T-spot.TB tests performed. The most common underlying malignancies in the QFT and T-spot.TB groups were acute myeloid leukemia (30% and 25%, respectively) and solid tumors (28% vs. 30%, respectively). The most common reasons for testing were pre-hematopoietic-cell transplantation (HCT) screening (42% with QFT and 31% with T spot.TB) or suspected pulmonary ATB (34% with QFT and 42% with T spot.TB). In the QFT group, 145/411 (35%) tests were indeterminate, while only 96/853 (11%) tests in the T-spot.TB group were invalid (P <0.001). The median ALC was 650 cells/µL in patients with an indeterminate result in the QFT group and 90 cells/µL in patients with an invalid test in the T-spot.TB group. A total of four patients were diagnosed with ATB at 1 year after testing. Figure 1 provides a flowchart describing IGRA testing results and development of ATB.ConclusionThe frequency of an inconclusive test result is significantly higher with QFT as compared with T-spot.TB for diagnosis of LTBI or ATB in cancer patients. A low ALC is likely a contributing factor in indeterminate QFT and invalid T spot.TBresults. Disclosures E. Ariza-Heredia, Oxford Immunotec: Grant Investigator, Research grant. R. F. Chemaly, Oxford Immunotec: Consultant and Grant Investigator, Research grant.

756. Targeting the Birth-Cohort of the Pre-antibiotic Era: A Proposal to Screen for Tuberculosis in Seniors in Arkansas

BackgroundApproximately 13 million (4.7%) people in the United States have latent TB infection (LTBI). Persons born prior to 1951 have disproportionately higher LTBI prevalence, and frequently experience delays in TB diagnosis and TB deaths. Nevertheless, this birth-cohort was overlooked in the 2016 US Preventive Service Task Force (USPSTF) recommendation for LTBI screening. The aims of this project are to (1) determine the LTBI prevalence in this birth-cohort, (2) assess TB complications prevented by LTBI screening in this birth-cohort, and (3) raise TB awareness among providers and the community.MethodsWe propose to: (1) Develop educational pamphlets for the physicians and community. (2) Screen 10,000 members of the target birth-cohort during their routine clinical visits for 1 year, using T-SPOT.TB. County health officers, the partners of Arkansas Department of Health, will enroll physicians in their jurisdictions to participate in TB screening. LTBI prevalence in the birth cohort will be determined, and TB complications will be compared among cohort TB cases that were screened to those not previously screened. (3) Incorporate LTBI and birth-cohort status in patient medical forms.ResultsIn our preliminary study, for the period 2009–2014, 142 of 326 TB cases (43.6% of all US-born TB cases) were reported from the target birth-cohort; 72.6% of the cases had unique genotype strains.ConclusionIf the LTBI prevalence in this birth cohort exceeds 8–10%, we recommend a nation-wide screening program for this birth-cohort. Even without treatment, we believe that screening and noting diagnosis of LTBI in the patient record will impact delayed diagnosis and mortality.Disclosures All authors: No reported disclosures.

2005. T-SPOT®.TB Test for Latent Tuberculosis Infection Diagnosis and Treatment Guidance in Thai Healthcare Professionals

BackgroundData on efficacy of T-SPOT®.TB Test (T-SPOT) in diagnosing latent tuberculosis infection (LTBI) and guiding isoniazid preventive therapy (IPT) among healthcare professionals (HCP) in tuberculosis (TB)-endemic settings are limited.MethodsA prospective study was conducted among Thai HCP undergoing T-SPOT in June 2016 (initial screening) and June 2017 (follow-up). Nine-month isoniazid preventive therapy (IPT) was offered among the HCP with positive T-SPOT. The incidence of TB and the rates of conversion and reversion of T-SPOT were evaluated during the 1-year follow-up period (June 2016 to June 2017).ResultsA total of 140 HCP underwent initial T-SPOT; the median age was 27 years (IQR 25–31 years), 89% were female and 23 (16%) were T-SPOT-positive. Eighty-nine HCP (64%) had both initial and follow-up T-SPOTs. Among the 89 HCP, the initial and follow-up rates of T-SPOT positivity were 19% (N = 17) and 24% (N = 21), respectively. The conversion and reversion rates were 10% (N = 9) and 6% (N = 5), respectively. All of the nine HCP (100%) with T-SPOT conversion reported significant contacts with patients who had active pulmonary TB without using appropriate personal protection equipment. During the 1-year follow-up period, incidence of TB were significantly higher among HCP with T-SPOT conversion compared with HCP with persistent positive T-SPOT, HCP with T-SPOT reversion and HCP with persistent negative T-SPOT [22 vs. 8 vs. 0 vs. 0 cases/100 person-years; P < 0.001]. Of the 17 HCP with positive initial T-SPOT, 8 (47%) completed IPT. The incidence of TB was significantly lower and the T-SPOT reversion rate was significantly higher among HCP completing IPT compared with HCP declining or not completing IPT (0 vs. 11 cases/100 person-years; P < 0.001 and 63% vs. 0%; P = 0.009, respectively).ConclusionT-SPOT could be used for diagnosing LTBI, guiding IPT and identifying HCP with subsequent risk for TB. The serial T-SPOT may be used for evaluating IPT efficacy.Disclosures All authors: No reported disclosures.

Comparison of IFN-γ Levels in Children with Tuberculosis Disease (TB) and Latent Tuberculosis Infection (LTBI).

AIM:This study aimed to evaluate the importance of IFN-γ in the diagnosis of pediatric TB and LTBI and to compare the IFN-γ levels.METHODS:We analysed 100 patients examined for possible M. tuberculosis infection or disease at the Institute of Respiratory Diseases in Children, Kozle, Skopje. Patients were divided into 2 groups: TB disease and LTBI. The following parameters were analyzed: demographic characteristics, history of previous exposure to active TB, BCG vaccination and presence of BCG scar, lung X-ray findings, tuberculin skin test by the Monteux method and the value of INF-γ according to the Quantiferon TB gold test, direct samples of acid-alcohol-resistant bacilli of sputum and Löwenstein Jensen cultures. Informed parental consent was obtained for each child included in the study.RESULTS:In the LTBI group 60.9% had a scar from the vaccination while in the TB group 50% had BCG scar. TST induration diameters in children with or without BCG scar were significantly larger in patients with active TB. Children with active TB had significantly higher IFN-γ levels than children with LTBI. The IFN-γ for the cut-off of 0.35 IU/ml, has 64% sensitivity for detection of LTBI, versus 80.6% sensitivity for active disease. Children with close TB contact had significantly higher IFN-γ levels. Correlation between TST induration diameter and IFN-γ levels was stronger in the TB group.CONCLUSION:IFN-γ levels are significantly higher in children with active TB, and children with close contact with TB patient. It has better sensitivity in active TB. Using both tests (IFN-γ and TST) can improve the diagnose of LTBI and TB in countries where vaccination with BCG is widespread.

Interferon-\u03b3 release assay as a sensitive diagnostic tool of latent tuberculosis infection in patients with HIV: a cross-sectional study

BackgroundIn developing countries, tuberculosis (TB) is a major public health problem and the leading cause of death among patients with HIV (Human Immunodeficiency Virus). Until 2001, the tuberculin skin test (TST) was the only available tool for the diagnosis of latent tuberculosis infection (LTBI), but false-negative TST results are frequently reported. Recently, the interferon-γ (IFN-γ) release assay (IGRA) has gained ground because it can detect the IFN-γ secreted by circulating lymphocytes T cells when stimulated by specific TB antigens. However, the role of IGRA in the diagnosis of LTBI in HIV-infected patients has not been well established.MethodsThis cross-sectional study compared the accuracy of TST (performed by the Mantoux method) and IGRA (QuantiFERON-TB Gold In-Tube, Cellestis, Carnegie, Australia) on the diagnosis of LTBI among patients with HIV. LTBI is defined by LTBI risk and at least one positive test (TST or IGRA), without clinical evidence of active TB. We also assessed the accuracy of TST and IGRA among HIV patients with high and low risk for LTBI.ResultsAmong 90 HIV patients, 80 met the study criteria for LTBI, fifty-nine (73.7%) patients were TST positive, 21 (26.2%) were negative, whereas 75 patients (93.7%) were IGRA positive, and five (6.2%) were negative. TST showed poor agreement with the diagnosis of LTBI (Kappa: 0.384), while IGRA demonstrated good agreement (Kappa: 0.769). Among 69 patients with high risk and 21 with low risk for LTBI, TST was positive in 48 (69.5%) and 11 (52.4%), while IGRA was positive in 68 (98.5%) and 7 (33.3%) patients, respectively. There were no association between TST and the level of risk (P = 0,191). Conversely, we observed a strong association between the IGRA and risk for LTBI (p < 0.001).ConclusionsCompared to TST, IGRA positivity is consistent with the risk of TB infection and seems to be a better diagnostic tool for LTBI in HIV-infected patients.

Screening for latent tuberculosis infection prior to biologic therapy in patients with chronic immune-mediated inflammatory diseases (IMID): Interferon-gamma release assay (IGRA) versus tuberculin skin test (TST)

BackgroundThe screening for latent tuberculosis infection (LTBI) is mandatory before initiating biologics in patients with chronic immune-mediated inflammatory disease (IMID). The recommendations are based on the tuberculin skin test (TST) and interferon-gamma release assay (IGRA). Aim of the workTo evaluate the agreement between the two tests in the diagnosis of LTBI and to identify risk factors associated with positive TST and IGRA results. Patients and methodsMedical records of 105 IMID patients going to receive a biologic agents were extracted in a cross sectional study (2015–2017). No biologics was undertaken before LTBI screening. All patients underwent IGRA and chest radiography. TST was performed in 94 cases. ResultsThe mean age of the patients was 47.7 ± 14.4 years and disease duration of 11.2 ± 7.6 years. Agreement between the 2 tests results was low (κ coefficient = 0.08). The sensitivity of TST and IGRA was equally low but the specificity of IGRA was higher. Replacing TST results by positive IGRA showed that number of patients who would take anti-tuberculous chemoprophylaxis will be significantly reduced by 46.5% (from 40.9% to 21.9%; p = 0.0002). TST results were significantly less positive for patients receiving immunosuppressives than for those receiving no treatment (35.1% vs 42.5%, p = 0.031). IGRA results were associated with absence of Bacilli Calemtte-Guérin vaccination. Age was the only risk factor for LTBI associated with both IGRA and TST positivity (p = 0.031, p = 0.011 respectively). ConclusionsTST and IGRA have a low agreement. Both tests should be included in the strategy to diagnose LTBI prior to biologic therapy in IMID patients.

A contact investigation after exposure to a child with disseminated tuberculosis mimicking inflammatory bowel disease.

PurposeTuberculosis (TB) is one of the most important diseases that cause significant mortality and morbidity in young children. Data on TB transmission from an infected child are limited. Herein, we report a case of disseminated TB in a child and conducted a contact investigation among exposed individuals.MethodsA 4-year-old child without Bacille Calmette-Guérin vaccination was diagnosed as having culture-proven disseminated TB. The child initially presented with symptoms of inflammatory bowel disease, and nosocomial and kindergarten exposures were reported. The exposed individuals to the index case were divided into 3 groups, namely household, nosocomial, or kindergarten contacts. Evaluation was performed following the Korean guidelines for TB. Kindergarten contacts were further divided into close or casual contacts. Chest radiography and tuberculin skin test or interferon-gamma-releasing assay were performed for the contacts.ResultsWe examined 327 individuals (3 household, 10 nosocomial, and 314 kindergarten contacts), of whom 18 (5.5%), the brother of the index patient, and 17 kindergarten children were diagnosed as having latent TB infection (LTBI). LTBI diagnosis was more frequent in the children who had close kindergarten contact with the index case (17.1% vs. 4.4%, P=0.007). None of the cases had active TB.ConclusionThis is the first reported case of TB transmission among young children from a pediatric patient with disseminated TB in Korea. TB should be emphasized as a possible cause of chronic diarrhea and failure to thrive in children. A national TB control policy has been actively applied to identify Korean children with LTBI.

First assessment of interferon gamma release assay results among healthcare workers at a general hospital in China.

China has a very high tuberculosis (TB) burden. The interferon-gamma release assay (IGRA) is more specific for the diagnosis of latent tuberculosis infection (LTBI) than the tuberculin skin test, especially among populations with a high degree of coverage by the BCG vaccine. To evaluate the first screening of healthcare workers (HCW) for LTBI using the IGRA at a general hospital in Beijing. A pilot screening program for LTBI was triggered by accidental contact between HCW and two patients with active TB in the emergency department (ED). Given the necessity of estimating the overall LTBI prevalence in the institution, a sample of 518 HCW was enrolled in our cross-sectional study. The second IGRA was repeated with 43 of the 121 HCW in the ED after exposure to index TB cases. Data on putative risk factors were collected with a self-administered questionnaire. The prevalence of LTBI in the targeted population was 21.8%. Differences in the prevalence of LTBI were significantly related to age, employment duration, and history of occupational exposure. A lack of childhood BCG vaccination was independently associated with the prevalence of LTBI (adjusted OR: 1.686, 95% CI: 1.045-2.723, P=.0325). No new LTBI was diagnosed 12 weeks postexposure. No HCW adopted the preventive treatment for LTBI. Considering the high morbidity of LTBI among HCW even in general hospitals, it is essential to formulate government policies and institutional operation protocols for the systematic screening, registration, and administration of prophylaxes for the control of LTBI.

Assessment of an ultra-sensitive IFNγ immunoassay prototype for latent tuberculosis diagnosis.

Worldwide there are about 1.7 billion individuals with latent tuberculosis infection (LTBI) and only 5% to 15% will develop active tuberculosis (TB). It is recommended to treat only those most at risk of developing active TB to avoid problems of drug resistance. LTBI diagnosis involves reviewing the individual's medical history, physical examination, and biological tests. Interferon gamma release assays (IGRA) can yield "undeterminate" or "uncertain" results, which makes clinical management decisions difficult. We assessed an ultra-sensitive immunoassay prototype based on single molecule array (SiMoA) technology to evaluate its overall performance, and in particular, its performance for indeterminate and uncertain positive or negative samples, as classified by the results from the current ELISA technique used for IFNγ quantification. We analyzed samples from hospitalized or consulting patients and healthcare workers from three hospitals in Paris, previously classified as negative (n = 30), positive (n = 35), uncertain negative (n = 25), uncertain positive (n = 31), or indeterminate (n = 30). We observed that with the SiMoA assay 83.3% of the indeterminate samples became interpretable and could be classified as negative, whereas 74% of uncertain positive samples were classified as positive. Most uncertain negative samples (72%) were reclassified as uncertain positive (68%) or positive (4%). The results suggest that the ultra-sensitive SiMoA IFNγ assay could represent a useful tool for the identification of true positive and negative samples among those giving indeterminate or uncertain results with the TB IGRA assay currently used.

Risk factors for latent tuberculosis infection in children in South Korea

ABSTRACTObjectives: In South Korea, latent tuberculosis infection (LTBI) screening is a critical strategy associated with efforts to reduce the incidence of tuberculosis (TB). Currently, only children with a known history of TB contact are considered as pediatric high-risk groups for LTBI, and consequently, LTBI screening is only provided to these children. However, to reduce the incidence of TB, the high-risk groups that undergo LTBI screening should be expanded. This study aimed to assess the risk factors for LTBI among children living in South Korea with no known history of TB contact for the identification of additional high-risk groups. We investigated the risk factors for LTBI among US visa applicant children, who undergo LTBI screening regardless of their TB contact history.Methods: We obtained data on demographic characteristics, medical history, Bacillus Calmette–Guerin (BCG) vaccination history, and results of LTBI screening for children aged 2–14 years. A tuberculin skin test was used for the diagnosis of LTBI, and an induration of 10 mm or greater was used to define a positive test. Adjusted odds ratios and 95% confidence intervals were calculated to determine the association between clinical and demographic variables and LTBI.Results: Of the 1,664 study participants, 91 (5.5%) had LTBI. The binary logistic regression analysis showed that children born in high TB burden foreign countries had the highest odds of LTBI when considering all the risk factors investigated. Increasing age, absence of BCG vaccination, and a previous diagnosis of asthma were also significant risk factors for LTBI.Conclusion: These results indicate that children born in high TB burden foreign countries should be considered a high-risk group for LTBI in South Korea; the inclusion of these children in LTBI screening should be considered.

Tuberculin skin test and QuantiFERON-Gold In Tube assay for diagnosis of latent TB infection among household contacts of pulmonary TB patients in high TB burden setting.

BackgroundWorld Health Organization (WHO) recommends systematic screening of high-risk populations, including household contacts (HHCs) of adult pulmonary tuberculosis (TB) patients, as a key strategy for elimination of TB. QuantiFERON-TB Gold In-Tube (QFT-GIT) assay and tuberculin skin test (TST) are two commonly used tools for the detection of latent tuberculosis infection (LTBI) but may yield differential results, affecting eligibility for TB preventive therapy.Materials and methodsA prospective cohort study of adult pulmonary TB patients and their HHCs were recruited in 2 cities of India, Pune and Chennai. HHCs underwent QFT-GIT (QIAGEN) and TST (PPD SPAN 2TU/5TU). A positive QFT-GIT was defined as value ≥0.35 IU/ml and a positive TST as an induration of ≥5 mm. A secondary outcome of TST induration ≥10mm was explored. Proportion positive by either or both assays, discordant positives and negatives were calculated; test concordance was assessed using percentage agreement and kappa statistics; and risk factors for concordance and discordance including age categories were assessed using logistic regression. Sensitivity and specificity was estimated by latent class model.ResultsOf 1048 HHCs enrolled, 869 [median (IQR) age: 27 years (15–40)] had both TST and QFT-GIT results available and prevalence of LTBI by QFT-GIT was 54% [95% CI (51, 57)], by TST was 55% [95% CI (52, 58)], by either test was 74% [95% CI (71, 77) and by both tests was 35% [95% CI (31, 38)]. Discordance of TST+/QFT-GIT- was 21% while TST-/QFT-GIT+ was 26%. Poor to fair agreement occurred with TST 5mm or 10mm cutoff (60 and 61% agreement with kappa value of 0.20 and 0.25 respectively). Test agreement varied by age, TST strength and induration cut-off. In multivariate analysis, span PPD was a risk factor for QFT-GIT+ and TST- while absence of BCG scar was for TST+ and QFT-GIT-. Being employed and exposure to TB case outside the household case were associated with positivity by both the tests. Sensitivity of TST and QFT-GIT to diagnose LTBI was 77% and 69%. Probability of having LTBI was >90% when both tests were positive irrespective of exposure gradient.ConclusionPrevalence of LTBI among HHCs of adult pulmonary TB patients in India is very high and varies by test type, age, and exposure gradient. In our high TB burden setting, a strategy to treat all HHCs or a targeted strategy whereby an exposure index is used should be assessed in future preventive therapy and vaccine studies as HHCs have several factors that place them at high risk for progression to TB disease.

Sequential strategy for the LTBI screening of newly-arrived immigrants in vulnerable social situations

IntroductionSome studies indicate high prevalences of latent tuberculosis infection (LTBI) in the immigrant population, which is relevant because 5–10% of cases will develop active tuberculosis. The objective of this study is to describe the results of a sequential strategy in the newly-arrived immigrant population for the diagnosis of LTBI using the tuberculin skin test (TST) and IGRAs. MethodsA retrospective descriptive study was carried out with immigrants between 6 and 35 years of age from shelters, referred to an international health unit between July 2013 and June 2016. The TST was performed and when it was ≥5mm, IGRAs were conducted. LTBI was defined as an IGRA ≥0.35IU/ml and normal chest X-ray. ResultsOf the 184 cases, 138 (75.0%) were men, 23.0 years of age. The most common geographical areas were: 63 (34.2%) from Asia, 42 (22.8%) from Eastern Europe and 41 (22.3%) from sub-Saharan Africa. The TST was ≥10mm in 79 cases (42.9%). The prevalence of LTBI using the sequential strategy was 33/184 (17.9%). Cohen's Kappa index (between TST≥10mm and IGRAs) was 0.226. ConclusionBasing LTBI screening on the TST alone could give rise to an overestimation. Some studies show that sequential screening would be the most cost-effective; this seems most evident in BCG-vaccinated populations.