Performance Evaluation of a New Automated Chemiluminescent Immunoanalyzer-Based Interferon-Gamma Releasing Assay AdvanSure I3 in Comparison With the QuantiFERON-TB Gold In-Tube Assay

BACKGROUND: The interferon-gamma (IFN-γ) releasing assay (IGRA) is widely used for latent tuberculosis infection (LTBI) diagnosis. We evaluated the analytical performance of a new automated chemiluminescent immunoanalyzer-based IGRA (CLIA-IGRA), AdvanSure I3 (LG Life Sciences, Seoul, Korea) and compared it with that of the QuantiFERON-TB Gold In-Tube (QFT-GIT) assay. METHODS: Repeatability and reproducibility were evaluated at four levels. Detection capability, including limit of blank (LoB), limit of detection (LoD), and limit of quantification (LoQ), was evaluated using IFN-γ standard material (National Institute for Biological Standards and Control code: 87/586). Agreement between the results of two assays was evaluated using 341 blood samples from healthcare workers and patients at a tertiary care hospital. To determine the cut-off value of CLIA-IGRA for diagnosing LTBI, the ROC curve was analyzed. RESULTS: Repeatability and reproducibility were 4.86–7.00% and 6.36–7.88% CV, respectively. LoB, LoD, and LoQ were 0.022, 0.077, and 0.249 IU/mL, respectively. IFN-γ values between CLIA-IGRA and QFT-GIT showed a strong correlation within the analytical measurable range of both assays, especially when the value was low. Qualitative comparison of the two assays yielded a 99.1% overall agreement (kappa coefficient=0.98). A cut-off value of 0.35 IU/mL was appropriate for diagnosing LTBI. CONCLUSIONS: CLIA-IGRA is a reliable assay for LTBI diagnosis, with performance similar to that of QFT-GIT.

Performance and correlation of QuantiFERON-TB Gold, T-SPOT.TB and tuberculin skin test in young children with tuberculosis exposure or tuberculosis disease

To evaluate the performance of interferon gamma release assays and tuberculin skin test in Bacillus Calmette-Guerin vaccinated young children. Methods: A cross-sectional study was conducted in healthy children younger than 5 years who were recently diagnosed with tuberculosis or had recent exposure to active tuberculosis. QuantiFERON-TB Gold, T-SPOT.TB and tuberculin skin test were performed in each patient. Results: Of the 60 children, median age 3.3 years, 17 had tuberculosis and 43 had recent tuberculosis exposure. Overall, 15 (25.0%) children had tuberculin skin test reaction =10 mm; 8 (13.3%) were positive by QuantiFERON-TB Gold In-Tube test, and 12 (20.0%) by T-SPOT.TB. Nineteen (31.7%) children had at least one positive test. There was a moderate agreement between interferon gamma release assays and tuberculin skin test. Conclusions: The positive rates of interferon gamma release assays and tuberculin skin test were low in young children who were infected with tuberculosis, supporting the management strategy of not testing children younger than 5 years. (IGRA) do not react to BCG and most NTM[2], are preferred to TST in older children and adults[3], but may be less reactive in young children with immature T-cell function. Due to the limited knowledge of IGRA in BCG-vaccinated young children, we evaluated the performance and correlation of IGRA tests and TST in young children in a high TB burden setting who received BCG vaccination at birth and recently diagnosed with LTBI, or with active TB.

Different Quantitative Interferon-γ Response in Active Tuberculosis of Various Primary Infection Sites

Performance and correlation of QuantiFERON-TB Gold, T-SPOT.TB and tuberculin skin test in young children with tuberculosis exposure or tuberculosis disease

To evaluate the performance of interferon gamma release assays and tuberculin skin test in Bacillus Calmette-Guerin vaccinated young children. Methods: A cross-sectional study was conducted in healthy children younger than 5 years who were recently diagnosed with tuberculosis or had recent exposure to active tuberculosis. QuantiFERON-TB Gold, T-SPOT.TB and tuberculin skin test were performed in each patient. Results: Of the 60 children, median age 3.3 years, 17 had tuberculosis and 43 had recent tuberculosis exposure. Overall, 15 (25.0%) children had tuberculin skin test reaction =10 mm; 8 (13.3%) were positive by QuantiFERON-TB Gold In-Tube test, and 12 (20.0%) by T-SPOT.TB. Nineteen (31.7%) children had at least one positive test. There was a moderate agreement between interferon gamma release assays and tuberculin skin test. Conclusions: The positive rates of interferon gamma release assays and tuberculin skin test were low in young children who were infected with tuberculosis, supporting the management strategy of not testing children younger than 5 years. (IGRA) do not react to BCG and most NTM[2], are preferred to TST in older children and adults[3], but may be less reactive in young children with immature T-cell function. Due to the limited knowledge of IGRA in BCG-vaccinated young children, we evaluated the performance and correlation of IGRA tests and TST in young children in a high TB burden setting who received BCG vaccination at birth and recently diagnosed with LTBI, or with active TB.

Utility of QuantiFERON®-TB gold In-Tube test compared with tuberculin skin test in diagnosing tuberculosis in Indian children with malnutrition

This prospective cohort study was conducted to compare the accuracy of QuantiFERON®-TB (QFT) Gold In-Tube test and tuberculin skin test (TST) in diagnosing tuberculosis (TB) in predominantly bacille Calmette–Guerin-vaccinated children with a high incidence of malnutrition. The sensitivity of the QFT versus the TST was 69.6% versus 52.9% for WHO-defined TB, with specificity of 86% versus 78.3%, respectively. The concordance of the TST and QFT was 79% overall (? = 0.430), 62.5% in those with WHO-defined TB and 85.7% in those without TB. Majority of the QFT+/TST ? discordance was seen in children with TB, whereas majority of the TST+/QFT ? discordance was seen in those without TB. The TST was more likely to be negative in children with moderate-to-severe malnutrition (P = 0.003) compared to the QFT, which was more likely to be positive in younger children. The significantly better performance of the QFT in malnourished children and those at younger ages supports its use for TB diagnosis in these subpopulations.

Diagnóstico de infección tuberculosa latente: comparación de la prueba de tuberculina y el quantiferon-tb gold plus en contactos domiciliarios de la Ciudad de Buenos Aires / Diagnosis of Latent Tuberculosis Infection: Comparison between the Tuberculin Test and Quantiferon-TB Gold Plus in Household Contacts from the City of Buenos Aires

La estrategia de control epidemiológico de la tuberculosis (TB) incluye tanto el diagnóstico y tratamiento precoz de los pacientes bacilíferos, como la identificación de aquellos con infección tuberculosa latente (ITBL) quienes representan el reservorio patógeno en la población. Objetivo: Comparar los resultados obtenidos utilizando la prueba de tuberculina (PPD) y el QuantiFERON-TB Gold Plus (QTF) en un grupo de contactos domiciliarios de pacientes con TB pulmonar bacilífera, de la Ciudad de Buenos Aires. Se utilizaron dos puntos de corte para considerar la PPD positiva: ≥ 5 mm (PPD-5) y ≥ 10 mm (PPD-10). Materiales y métodos: Se extrajeron muestras de sangre para QTF en contactos domiciliarios de pacientes con TB bacilífera, seguido inmediatamente de la aplicación de PPD. Se consideró al QTF como la prueba de referencia a partir de la cual comparar la PPD calculando la sensibilidad (S), especificidad (E), valor predictivo positivo (VPP), valor predictivo negativo (VPN) y coeficiente de correlación Kappa. Resultados: Se incluyeron 48 contactos (33 mujeres, 69%), edad 38.8 ± 19 años, 27 (56%) argentinos, 18 (38%) bolivianos y 3(6%) peruanos, correspondientes a 37 casos de TB. Un solo contacto refirió no haberse aplicado la BCG, en 44 se objetivó la cicatriz. El QTF resultó positivo en 23 (47.9%) e indeterminado en 2 casos (4.2%). Excluyendo del análisis a los indeterminados, no hubo diferencias significativas entre contactos con QTF positivo y negativo al considerar la edad (33.8 ± 16 vs 42.1 ± 20 años), nacionalidad: argentinos (12 de 26, 46%) vs extranjeros (11 de 20, 55%) y sexo: mujeres (18 de 32, 56%) vs hombres (5 de 14, 36%). Utilizando PPD-5 hubo 28 (60.9%) positivos y 13 (28.3%) con PPD-10. Comparando PPD-5 vs PPD-10: S = 73.9 vs 34.8%, E = 52.2 vs 78.3%, VPP = 60.1 vs 61.5% y VPN = 66.7 vs 54.5%. Los resultados coincidentes (positivos y negativos) entre QTF y PPD fueron 29 (63%) para PPD-5 y 26 (56.5%) con PPD-10. Expresados con el coeficiente Kappa muestran concordancia débil (0.261) e insignificante (0.130), respectivamente. Conclusiones: considerando al QTF como el método de referencia por su mayor especificidad, la PPD-5, aunque menos específica, resultó más sensible que la PPD-10 para diagnosticar infección tuberculosa latente en el grupo de contactos domiciliarios estudiados

Diagnosis of Latent Tuberculosis Infection: Comparison between the Tuberculin Test and Quantiferon-TB Gold Plus in Household Contacts from the City of Buenos Aires / Diagnóstico de infección tuberculosa latente: comparación de la prueba de tuberculina y el quantiferon-tb gold plus en contactos domiciliarios de la Ciudad de Buenos Aires

The epidemiological control strategy of tuberculosis (TB) includes both the diagnosis and early treatment of baciliferous patients and the identification of individuals with latent tuberculosis infection (LTBI), who represent the pathogen reservoir within the population. Objective: To compare the results obtained using the tuberculin test (PPD, Purified Protein Derivative) and the QuantiFERON-TB Gold Plus (QTF) in a group of household contacts of patients with bacillary pulmonary TB in the city of Buenos Aires. We used two cutoff points to consider PPD as positive: ≥ 5 mm (PPD-5) and ≥ 10 mm (PPD-10). Materials and Methods: Blood samples for QTF were taken from household contacts of patients with bacillary TB, followed immediately by the application of PPD. The QTF was considered as the reference test from which to compare the PPD by calculating sensitivity (S), specificity (E), positive predictive value (PPV), negative predictive value (NPV) and Kappa correlation coefficient. Results: 48 contacts were included (33 women, 69%), age 38.8 ± 19 years, 27 (56%) Argentinean, 18 (38%) Bolivians and 3 (6%) Peruvians, 37 were cases of TB. Only one contact informed She/she hadn't received the BCG; and 44 subjects showed the BCG scar. The QTF was positive in 23 individuals (47.9%) and undetermined in 2 cases (4.2%). Excluding the indeterminate cases from the analysis, there were no significant differences between positive and negative QTF contacts regarding age (33.8 ± 16 vs. 42.1 ± 20 years), nationality: Argentinean (12 of 26.46%) vs. foreigners (11 of 20.55%) and sex: women (18 of 32, 56%) vs. men (5 of 14, 36%). There were 28 (60.9%) positive cases with PPD-5 and 13 (28.3%) with PPD-10. Comparison between PPD-5 vs. PPD-10: S = 73.9 vs. 34.8%, E = 52.2 vs. 78.3%, PPV = 60.1 vs. 61.5% and NPV = 66.7 vs. 54.5%. The coincident results (positive and negative) between QTF and PPD were 29 (63%) for PPD-5 and 26 (56.5%) for PPD-10. Expressed with the Kappa coefficient, they show weak (0.261) and insignificant (0.130) concordance, respectively. Conclusions: Considering the QTF as the reference method for its higher specificity, PPD-5, although less specific, was more sensitive than PPD-10 for the diagnosis of latent tuberculosis infection in the group of household contacts under study.

Potencial do teste IGRA (Interferon Gama Release Assay) para o diagnóstico de tuberculose ocular. Revisão e análise comparativa com o teste tuberculínico cutâneo (PPD) / The potential of the IGRA (Interferon Gamma Release Assay) test for the diagnosis of ocular tuberculosis. Review and comparative analysis with the tuberculosis skin test

Resumo A detecção precisa da infecção latente por tuberculose está se tornando cada vez mais importante devido ao aumento do uso de medicamentos imunossupressores e da epidemia do vírus da imunodeficiência humana, o que aumentou o risco de reativação à tuberculose ativa (TB). O Teste IGRA QuantiFERON® TB Gold apresenta vantagens frente ao teste de PPD como por exemplo, requer somente uma coleta de amostra sanguínea ; não há necessidade que o paciente retorne ao laboratório para leitura e interpretação dos resultados; Os resultados são objetivos, não requerem interpretação do leitor ou interferência de critérios subjetivos; trata-se de um teste in vitro, portanto não há "efeito booster" (potenciação da reação tuberculínica); o teste não é afetado por vacinação prévia por BCG ou infecção por outras espécies de micobactérias. Limitações são descritas, apesar de raras, como reações cruzadas deste método com infecções por algumas espécies de micobactérias não-tuberculosis (incluindo Mycobacterium kansasii, Mycobacterium szulgai e Mycobacterium marinum). Ainda há poucos dados sobre o teste IGRA em certas populações, como por exemplo, em crianças, pacientes imunocomprometidos e mulheres grávidas. Nestes grupos, a interpretação do teste pode ser difícil e mais estudos se fazem necessários.

Abstract Precise detection of latent tuberculosis infection is becoming increasingly important due to increased use of immunosuppressive drugs and the human immunodeficiency virus epidemic , which increased the risk of reactivation to active tuberculosis (TB).The QuantiFERON® TB Gold IGRA Test has advantages over the skin test for TB, otherwise known as a Mantoux tuberculin test, for example, requires only a blood sample collection; there is no need for the patient to return to the laboratory for reading and interpretation of the results; The results are objective, do not require interpretation of the reader or interference of subjective criteria; it is an in vitro test, so there is no "booster effect" (potentiation of the tuberculin reaction); the test is not affected by prior BCG vaccination or infection with other species of mycobacteria. Limitations are described, although rare, as cross-reactions of this method with infections by some species of non-tuberculosis mycobacteria (including Mycobacterium kansasii, Mycobacterium szulgai and Mycobacterium marinum). There is still little data on the IGRA test in certain populations, such as in children, immunocompromised patients and pregnant women. In these groups, the interpretation of the test can be difficult and more studies are needed.

The Performance of the Agility System for Interferon Gamma Release Assay Using QuantiFERON TB Gold In-Tube Assay / 임상검사와정도관리

BACKGROUND: As stated in ‘The Action Strategy for Tuberculosis-Free Korea,’ last March, high-throughput, large-scale analytical instruments for interferon gamma release assays (IGRA) are demanded by many clinical laboratories using the QuantiFERON-TB Gold In-Tube assay (Cellestis/Qiagen, Australia). Agility (Dynex Technologies, USA) is an automated high-throughput enzyme linked immunosorbent assay analyser. The present study aimed to evaluate its accuracy and speed. METHODS: Pooled plasma was prepared using samples obtained after IGRA testing. Analyses of precision, linearity, cut-off evaluation, and comparison with conventional methods were performed for multiple Agility instruments according to the Clinical and Laboratory Standards Institute EP5-A3, EP6-A, EP9-A3 and EP12-A2 guidelines. The turnaround time and throughput were also analysed. RESULTS: The coefficient of variation range was 2.48%–4.0%, 7.01%–11.17%, and 9.69%–14.84% for the repeatability, between-run precision, and between-day precision analyses, respectively. The linearity ranged from 0 to 10.541. Comparison analysis presented a high concordance of Agility with the conventional instrument, DS2 (Dynex Technologies), and manual method for IGRA. The cut-off value of 0.35 IU/mL was well compatible with the C50. It was identified that the C50±20% contained the C5–C95 interval. The average turnaround time was 3.84 hours, from the submission of pre-treated samples to the reporting of results. The throughput was determined to be 290 tests during a routine working time of 8 hours. CONCLUSIONS: Agility showed high precision, linearity, concordance, and had a 2.5 times faster throughput than with the conventional and manual method. It could be useful for large-scale IGRA testing in latent tuberculosis infection screening project. Samples within C50±20% are suspected to show relatively low reporducible results of high inversion between postivie and negative.

A Feasibility Study for Diagnosis of Latent Tuberculosis Infection Using an IGRA Point-of-Care Platform in South Korea

PURPOSE: This study aimed to evaluate ichroma™ IGRA-TB, a novel point-of-care platform for assaying IFN-γ release, and to compare it with QuantiFERON-TB Gold In-Tube (QFT-GIT) for identifying Mycobacterium tuberculosis (M. tb) infection. MATERIALS AND METHODS: We recruited 60 healthy subjects, and blood samples were obtained in QFT-GIT blood collection tubes. The blood collection tubes were incubated at 37℃, and culture supernatant was harvested after 18–24 hours. IFN-γ responses were assessed by the ichroma™ IGRA-TB cartridge and the QFT-GIT IFN-γ enzyme-linked immunosorbent assay. Three active TB patients were recruited as a positive control for M. tb infection. RESULTS: The area under the receiver operating characteristic curve of the ichroma™ IGRA-TB test for differentiating between infected and non-infected individuals was 0.9706 (p < 0.001). Inconsistent positivity between the two tests was found in three participants who showed weak positive IFN-γ responses ( < 1.0 IU/mL) with QFT-GIT. However, the two tests had excellent agreement (95.2%, κ=0.91, p < 0.001), and a very strong positive correlation was observed between the IFN-γ values of both tests (r=0.91, p < 0.001). CONCLUSION: The diagnostic accuracy demonstrated in this study indicates that the ichroma™ IGRA-TB test could be used as a rapid diagnostic method for detecting latent TB infection. It may be particularly beneficial in resource-limited places that require cost-effective laboratory diagnostics.

Multiple Skin Colored Nodules on both Legs in Patient with Positive QuantiFERON®-TB Gold Test

Nodular tuberculid (NT) was originally described by Jordaan et al. in 2000 in 4 patients from South Africa. It appeared as nodules on the legs; the pathologic changes were situated in the deep dermis and adjacent subcutaneous fat. A 34-year-old woman visited our hospital with subcutaneous skin-colored or slightly erythematous round to oval nodules. Skin biopsies revealed granulomatous inflammation at the dermo-subcutaneous junction with vasculitis. Chest X-ray, tuberculosus (TB)-polymerase chain reaction and TB culture of the skin specimen were normal. A QuantiFERON®-TB Gold test (QUIAGEN, Germany) was positive, which suggested a diagnosis of latent TB infection. The patient was treated with anti-TB medication and her condition has not recurred. Herein, we report a case of a patient with latent TB diagnosed by a positive QuantiFERON®-TB Gold test whose skin lesions had the clinical and histopathologic features of NT.

Multiple Skin Colored Nodules on both Legs in Patient with Positive QuantiFERON®-TB Gold Test

Nodular tuberculid (NT) was originally described by Jordaan et al. in 2000 in 4 patients from South Africa. It appeared as nodules on the legs; the pathologic changes were situated in the deep dermis and adjacent subcutaneous fat. A 34-year-old woman visited our hospital with subcutaneous skin-colored or slightly erythematous round to oval nodules. Skin biopsies revealed granulomatous inflammation at the dermo-subcutaneous junction with vasculitis. Chest X-ray, tuberculosus (TB)-polymerase chain reaction and TB culture of the skin specimen were normal. A QuantiFERON®-TB Gold test (QUIAGEN, Germany) was positive, which suggested a diagnosis of latent TB infection. The patient was treated with anti-TB medication and her condition has not recurred. Herein, we report a case of a patient with latent TB diagnosed by a positive QuantiFERON®-TB Gold test whose skin lesions had the clinical and histopathologic features of NT.

Clinical Usefulness of Monitoring Cytomegalovirus-Specific Immunity by Quantiferon-CMV in Pediatric Allogeneic Hematopoietic Stem Cell Transplantation Recipients

Cytomegalovirus (CMV) is a well-established cause of morbidity and mortality in pediatric recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT). CD8⁺ T-cells are important for controlling CMV infection. We conducted a prospective pilot study to investigate the clinical utility of measuring the CMV-specific T-cell immune response using the QuantiFERON-CMV assay (QF-CMV) in pediatric allo-HSCT recipients. Overall, 16 of 25 (64%) patients developed CMV infection. QF-CMV was evaluated in these 16 patients during the early and late phases of the first CMV infection post allo-HSCT. Whereas the initial QF-CMV results during the early phase of CMV infection did not correlate with the course of the corresponding infection, the QF-CMV results post resolution of the first CMV infection correlated with the recurrence of CMV infection until 12 months post allo-HSCT; no recurrent infections occurred in the four QF-CMV-positive patients, while recurrent infections manifested in five of eight QF-CMV-negative (62.5%) and all three QF-CMV-indeterminate patients (P=0.019). In spite of the small number of patients examined, this study supports the potential application of monitoring CMV-specific T-cell immunity using the QF-CMV assay to predict the recurrence of CMV infection in pediatric allo-HSCT recipients.

СҮРЬЕЭГИЙН ДАЛД ХАЛДВАРЫН ТАРХАЛТЫГ ТОДОРХОЙЛЖ, ТҮҮНД НӨЛӨӨЛӨХ ЗАРИМ ХҮЧИН ЗҮЙЛИЙН ЭРСДЛИЙГ ҮНЭЛСЭН НЬ / Шинэ санаа Шинэ нээлт

@#BACKGROUND. 2.3 billion Individuals have latent TB infection(LTBI), up to 10 million new cases of TB arise and killing nearly 2 million individuals around this globe, annually [1,2]. In Mongolia, tuberculinskin test is used to detection of mycobacterial infection, which has many disadvantages. Interferon gamma release assay (IGRA, QFT-G), a method advised by WHO, is the most reliable detection of latent infection. If we can detect LTBI in childhood, it is possible to prevent from active TB decreasing prevalence in the future. That is why it is important to screen the LTBI among children. GOAL: To estimate the prevalence of LTBI among 6-13 age children and to define the LTBI risk factors. Methods: We enrolled 9126 children for our study, indicating a possible estimation for LTBI prevalence among 6-13 age children in Ulaanbaatar city. Under ethical permission, our study was performed, as well as the consent of parents and children. We determined the LTBI by using QFT-G. We took a questionnaire about a socio-economic status, a history of TB contact and also conducted anthropometric measurements in all participants. The study design was a descriptive, cross-sectional and a case-control which based on QFT-G results. SPSS version 20.0.0 was used for statistical analyses. RESULTS: Regardingthe QFT-G test, 8214(90%) number of children were negative, 908 (10%) were positive, 4 (<0.1%) samples were indeterminable. There were statistically significant differences between control and case group in some questionnaire of socio-economic status. No significant difference was seen between two groups in all anthropometric measurements. In multinomial logistic regression, a tuberculosis contact, a household type, and passive smoking were identified as independent LTBI risk factors (p<0.01). CONCLUSIONS: The LTBI prevalence is high (10%) in school-age children living in Ulaanbaatar. It has increased at 6-13 age (p<0.05). Several important risk factors for LTBI in school age children elicited. Most powerful risk factors were tuberculosis contact (p<0.001), type of residence (p<0.05) and passive smoking (p<0.001).

Comparison of the tuberculin skin test and the QuantiFERON-TB Gold test in detecting latent tuberculosis in health care workers in Iran / 한국역학회지

OBJECTIVES: The tuberculin skin test (TST) and the QuantiFERON-TB Gold test (QFT) are used to identify latent tuberculosis infections (LTBIs). The aim of this study was to determine the agreement between these two tests among health care workers in Iran. METHODS: This cross-sectional study included 177 tuberculosis (TB) laboratory staff and 67 non-TB staff. TST indurations of 10 mm or more were considered positive. The Student's t-test and the chi-square test were used to compare the mean score and proportion of variables between the TB laboratory staff and the non-TB laboratory staff. Kappa statistics were used to evaluate the agreement between these tests, and logistic regression was used to assess the risk factors associated with positive results for each test. RESULTS: The prevalence of LTBIs according to both the QFT and the TST was 17% (95% confidence interval [CI], 12% to 21%) and 16% (95% CI, 11% to 21%), respectively. The agreement between the QFT and the TST was 77.46%, with a kappa of 0.19 (95% CI, 0.04 to 0.34). CONCLUSIONS: Although the prevalence of LTBI based on the QFT and the TST was not significantly different, the kappa statistic was low between these two tests for the detection of LTBIs.

Discordance between Tuberculin Skin Test and Interferon-gamma Release Assays for Diagnosis of Tuberculosis Infection in Korean Children

PURPOSE: There is a the great diagnostic challenge in pediatric tuberculosis especially in high burden setting. The purpose of this preliminary study is to evaluate the agreement between tuberculin skin test (TST) and interferon-gamma release assay (IGRA) including T-SPOT®-TB and QuantiFERON®-TB Gold (QFT-G) in Korean children. METHOD: This retrospective study included children and adolescents who visited to Asan Medical Center to evaluate tuberculosis infection using at least two assays of TST, T-SPOT.TB and QFT-G, from January 2014 to April 2015. RESULTS: A total of 20 patients were included, whose median age was 13.3 years (range, 3.8-18.1 years), and all of them had history of BCG vaccination. Eleven patients had underlying diseases including 7 patients with immunosuppressant medication. The concordance rate between T-SPOT.TB and QFT-G was 90%. However, the concordance rate between TST and T-SPOT.TB was 50%, and between TST and QFT-G was 42.9%. Specificity for the diagnosis of tuberculosis infection of T-SPOT.TB, QFT-G, and TST was 93.3%, 86.7%, and 58.3%, respectively. CONCLUSIONS: Although there was a discrepancy between TST and IGRA to diagnose tuberculosis, agreement between T-SPOT.TB and QFT-G was relatively high. Further prospective study to validate the clinical usefulness of each assay for immunologic evidence of tuberculosis infection in Korean children will be mandatory.

Comparison of interferon gamma release assay & tuberculin skin tests for diagnosis of latent tuberculosis in patients on maintenance haemodialysis.

Background & objectives: Tuberculosis (TB) is a common infection in patients on haemodialysis. There is a definite role of treatment of latent TB (LTB) in these patients. However, diagnosis of LTB in these patients by tuberculin skin test (TST) is unreliable. There is suggestion that interferon gamma release assay (IGRA) will be more reliable test for diagnosis of LTB in this setting. Thus, we evaluated value of IGRA and TST for the diagnosis of LTB in patients on dialysis in an Indian setting. Methods: Patients with end stage kidney disease on dialysis were included. Patients with active TB were excluded. Each patient was subjected to TST (induration of ≥10 mm was taken as positive) and QuantiFERON TB Gold In-Tube test (QFT-GIT) for diagnosis of LTB. Results: A total of 185 patients were included; 129 (69.7%) were males and mean age was 36.7 ± 12.3 yr. Past history of TB was present in 18 (9.7%) patients. One hundred and thirty four (72.4%) patients had scar of BCG vaccination. QFT-GIT test was positive in 66 (36%), TST in 32 (17%) and both in 13 (7%) patients. Of the 66 patients positive with QFT-GIT, only 13 (19.6%) were positive for TST. Of the 32 patients positive with TST, only 13 (40.6%) were positive with QFT-GIT; 100 (54%) patients were negative for both the tests. Overall, 85 (45.9%) patients were positive for either of the two tests. Poor agreement was shown between the two methods. On logistic regression analysis, odds of QFT-GIT to be positive in patients with BCG vaccination was 1.23 and with history of TB 0.99, both being insignificant. odds of tuberculin skin test to be positive in patients with BCG vaccination was 1.04 and with history of TB 0.99, both again being insignificant. Interpretation & conclusions: Our findings showed that more number of patients (36%) on haemodialysis were positive for QuantiFERON Gold In-Tube test as compared to TST (17%). There was poor agreement between the two tests. no significant effect of BCG vaccination and history of TB in past was observed on both tests.

Custo-efetividade da prova tuberculínica versus QuantiFERON-TB Gold-In-Tube no diagnóstico e tratamento da infecção latente tuberculosa em profissionais de saúde da Atenção Básica no Brasil / Cost-effectiveness of tuberculin skin test versus QuantiFERON-TB Gold-In-Tube in the diagnosis and treatment of latent tuberculosis infection in the primary health care workers in Brazil

Os profissionais da área da saúde formam um dos grupos mais vulneráveis à infecção pelo Mycobacterium tuberculosis (Mtb). Segundo estimativas da Organização Mundial de Saúde (OMS), 8,8 milhões de pessoas estavam infectadas pelo Mtb e ocorreram 1,4 milhão de óbitos por tuberculose (TB) em 2010. A identificação de pessoas com Infecção Latente Tuberculosa (ILTB) é considerada pela OMS como uma prioridade no controle da doença, especialmente em países em desenvolvimento em que a incidência da doença ativa tem apresentado redução. O objetivo do presente trabalho foi avaliar, no Brasil, o custo-efetividade dos testes Prova Tuberculínica (PT) e Quantiferon TB Gold-In-Tube (QTF-GIT) no diagnóstico e tratamento da ILTB em profissionais de saúde atuantes na atenção básica, sob a perspectiva do Sistema Único de Saúde (SUS), comparando cinco estratégias que incluem o QTF-GIT, distintos pontos de corte para a PT e uso sequencial dos dois testes; e analisar o impacto do tabagismo sobre o risco de ILTB entre os profissionais de saúde, destacando-se a categoria da Enfermagem. Foi realizada uma avaliação econômica completa do tipo custo-efetividade, conduzida considerando uma coorte hipotética de 10.000 profissionais de saúde atuantes na atenção básica, com horizonte temporal restrito a um ano. Um modelo analítico de decisão, caracterizado por uma árvore de probabilidades de eventos, foi desenvolvido utilizando o software TreeAge ProTM 2013 para simular os resultados clínicos e impactos econômicos em saúde da nova tecnologia diagnóstica (QTF-GIT) versus a PT tradicional. Esse modelo simulou cinco estratégias diagnósticas para detecção e tratamento da ILTB: (a) PT, usando ponto de corte de 5mm; (b) PT, usando ponto de corte de 10 mm; (c) teste QTF-GIT; (d) PT, com ponto de corte de 5mm, seguida de teste QTF-GIT quando PT positiva; (e) PT, com ponto de corte de 10mm, seguida de teste QTF-GIT quando PT positiva. Foi realizada análise de sensibilidade determinística univariada. Na determinação dos fatores associados à ILTB, foi elaborado um modelo de regressão logística múltipla com seleção hierarquizada, utilizando o software Stata. A estratégia mais custo-efetiva foi a PT no ponto de corte ≥10mm, considerando como medida de desfecho tanto o número de indivíduos corretamente classificados pelos testes assim como o número de casos de TB evitados. A utilização isolada do QTF-GIT revelou-se a estratégia de menor eficiência, com RCEI= R$ 343,24 por profissional corretamente classificado pelo teste. Encontrou-se risco à ILTB significantemente maior para sexo masculino [OR=1,89; IC 95%:1,11-3,20], idade ≥ 41 anos [OR=1,56; IC 95%: 1.09-2,22], contato próximo com familiar com TB [OR=1,55; IC 95%: 1.02-2,36], status do tabagismo fumante [OR=1,75; IC 95%: 1.03-2,98] e categoria profissional da Enfermagem [OR=1,44; IC 95%: 1.02-2,03]. Concluiu-se que a PT no ponto de corte de 10mm é a estratégia diagnóstica mais custo-efetiva para ILTB entre os profissionais de saúde na atenção básica e que a ILTB está associada ao hábito do tabagismo e à categoria profissional de Enfermagem

Health professionals form one of the groups most vulnerable to infection by Mycobacterium tuberculosis (Mtb). According to estimates by the World Health Organization (WHO), 8.8 million people were infected with Mtb and were 1.4 million deaths from TB in 2010. The identification of persons with Latent Tuberculosis Infection (LTBI) is considered by WHO as a priority in the control of disease, especially in developing countries where the incidence of active disease has shown reduction. The aim of this study was to evaluate, in Brazil, the cost-effectiveness of tests Tuberculin Skin Test (TST) and Quantiferon TB Gold-In-Tube (QFT-GIT) in the diagnosis and treatment of LTBI in health professionals working in primary care from the perspective of SUS, comparing five strategies that include the QFT -GIT, different cutoff points for TST and sequential use of two tests; and analyze the impact of smoking on the risk of LTBI among health professionals, highlighting the category of Nursing. A full economic assessment of the type cost-effectiveness was performed, conducted considering a hypothetical cohort of 10,000 health professionals working in primary care, with limited time horizont of one year. A decision analytical model, characterized by a tree of probabilities of events, was developed using the TreeAge ProTM software 2013 (TreeAge Software Inc, Williamstown, MA, USA) to simulate the clinical and economic impacts on health of new diagnostic technology (QFT -GIT) versus the traditional TST. This model simulated five diagnostic strategies for detection and treatment of LTBI (a) TST, using a cut-off of 5 mm; (B) TST, using 10 mm cut-off currently recommended by the TNP; (C) QFT-GIT test; (D) TST, with a cut-off of 5 mm, followed by QFT-GIT test when positive TST; (E) TST, with a cut-off point of 10 mm, followed by QFT-GIT test when positive TST. Univariate deterministic sensitivity analysis was performed to assess the robustness of the results. In determining the factors associated with LTBI, a multiple logistic regression model with hierarchical selection was made, using the Stata software. TST strategy at the cut-off ≥ 10mm was the most cost-effective strategy, while the QFT-GIT alone was the most effective strategy, but showed higher cost. It was found to significantly greater risk for LTBI male [OR = 1.89; 95% CI: 1.11 to 3.20], age ≥ 41 years [OR = 1.56; 95% CI: 1.09-2,22], close contact with a family with TB [OR = 1.55; 95% CI: 1.02-2,36], the smoker smoking status [OR = 1.75; 95% CI: 1.03-2,98] and professional nursing category [OR = 1.44; 95% CI: 1.02-2,03]. It was concluded that TST in 10mm cut-off is the diagnostic strategy more cost-effective for LTBI among health professionals in primary care and that LTBI is associated with the smoke and professional category nurse

Serial QuantiFERON-TB Gold In-Tube assay and tuberculin skin test to diagnose latent tuberculosis in household Mexican contacts: conversion and reversion rates and associated factors using conventional and borderline zone definitions

A cohort of 123 adult contacts was followed for 18‐24 months (86 completed the follow-up) to compare conversion and reversion rates based on two serial measures of QuantiFERON (QFT) and tuberculin skin test (TST) (PPD from TUBERSOL, Aventis Pasteur, Canada) for diagnosing latent tuberculosis (TB) in household contacts of TB patients using conventional (C) and borderline zone (BZ) definitions. Questionnaires were used to obtain information regarding TB exposure, TB risk factors and socio-demographic data. QFT (IU/mL) conversion was defined as <0.35 to ≥0.35 (C) or <0.35 to >0.70 (BZ) and reversion was defined as ≥0.35 to <0.35 (C) or ≥0.35 to <0.20 (BZ); TST (mm) conversion was defined as <5 to ≥5 (C) or <5 to >10 (BZ) and reversion was defined as ≥5 to <5 (C). The QFT conversion and reversion rates were 10.5% and 7% with C and 8.1% and 4.7% with the BZ definitions, respectively. The TST rates were higher compared with QFT, especially with the C definitions (conversion 23.3%, reversion 9.3%). The QFT conversion and reversion rates were higher for TST ≥5; for TST, both rates were lower for QFT <0.35. No risk factors were associated with the probability of converting or reverting. The inconsistency and apparent randomness of serial testing is confusing and adds to the limitations of these tests and definitions to follow-up close TB contacts.

Tuberculin skin test and interferon-gamma release assay values are associated with antimicrobial peptides expression in polymorphonuclear cells during latent tuberculous infection

It has been reported that patients with progressive tuberculosis (TB) express abundant amounts of the antimicrobial peptides (AMPs) cathelicidin (LL-37) and human neutrophil peptide-1 (HNP-1) in circulating cells, whereas latent TB infected donors showed no differences when compared with purified protein derivative (PPD) and QuantiFERON®-TB Gold (QFT)-healthy individuals. The aim of this study was to determine whether LL-37 and HNP-1 production correlates with higher tuberculin skin test (TST) and QFT values in TB household contacts. Twenty-six TB household contact individuals between 26-58 years old TST and QFT positive with at last two years of latent TB infection were recruited. AMPs production by polymorphonuclear cells was determined by flow cytometry and correlation between TST and QFT values was analysed. Our results showed that there is a positive correlation between levels of HNP-1 and LL-37 production with reactivity to TST and/or QFT levels. This preliminary study suggests the potential use of the expression levels of these peptides as biomarkers for progression in latent infected individuals.