Latent tuberculosis screening before kidney transplantation in the South of Brazil / Rastreamento de tuberculose latente antes do transplante renal no Sul do Brasil

Abstract Background: Tuberculosis (TB) is a prevalent infection after kidney transplantation (KT) in high-burden countries. Latent tuberculosis infection (LTBI) screening includes previous TB history, chest radiograph findings, and tuberculin test (TST) and/or interferon-gamma release assays (IGRAs) results. We aimed to compare our routine LTBI screening of KT candidates and living donors (LD) with their IGRA results, and evaluate if this would improve isoniazid (INH) treatment referral. Methods: We evaluated adult KT candidates and LD with complete routine LTBI screening and QuantiFERON-TB® Gold In-Tube (QFT) testing. Blood samples were collected from April 4th, 2014 to October 31st, 2018, with follow-up until October 31st, 2019. Results: There were 116 KT recipients, with 30% QFT-positive results. Positive QFT was associated with past TB history (p=0.007), positive TST (p<0.0001), residual radiographic lesions (p=0.003), and diabetes (p=0.035). There were 25 LD, 40% had positive QFT. Positive QFT was associated with a positive TST (p=0.002). Positive QFT results increased INH referral in 80%. Post-transplant TB incidence was 2.6% in a median follow-up of 2 (1-33) months. No variables were associated with post-transplant TB. TB patients had inferior, although non-significant, 5-year graft survival (66.7% vs. 76.5%) (p = 0.402). Conclusion: In the present study, the association of QFT to our routine LTBI screening incremented INH treatment referral, but there was still a high incidence of post-transplant TB, possibly related to other forms of infection, such as new exposure and donor transmission.

Resumo Histórico: Tuberculose (TB) é uma infecção relativamente comum pós-transplante renal (TR) em países com alta prevalência da doença. O rastreamento de infecção latente por tuberculose (ILTB) inclui histórico prévio de TB, achados de radiografia do tórax, resultados do teste tuberculínico (TT) e/ou de ensaio de liberação de interferon-gama (IGRAs). Nosso objetivo foi comparar nossa avaliação de rotina de candidatos ao TR e doadores vivos (DV) com seus resultados de IGRA, avaliando se aumentaria o encaminhamento para tratamento com isoniazida (INH). Métodos: Avaliamos candidatos adultos ao TR e DV com rastreamento para ILTB de rotina completo e coleta de testes QuantiFERON-TB® Gold In-Tube (QFT). Coletamos amostras sanguíneas de 4 de Abril, 2014 - 31 de Outubro, 2018, com acompanhamento até 31 de Outubro, 2019. Resultados: Avaliamos 116 receptores de TR, 30% sendo QFT-positivo. QFT positivo foi associado ao histórico prévio de TB (p=0,007), TT positivo (p<0,0001), lesões radiográficas residuais (p=0,003), diabetes (p=0,035). Avaliamos 25 DV, 40% apresentaram QFT positivo. QFT positivo foi associado a TT positivo (p=0,002). Resultados positivos do QFT aumentaram o encaminhamento para INH em 80%. A incidência de TB pós-transplante foi 2,6% em uma mediana de acompanhamento de 2 (1-33) meses. Nenhuma variável foi associada à TB pós-transplante. Pacientes com TB tiveram sobrevida do enxerto em 5 anos inferior, embora não-significativa (66,7% vs. 76,5%) (p = 0,402). Conclusão: Neste estudo, a associação do QFT à nossa avaliação de ILTB de rotina aumentou o encaminhamento para tratamento com INH, mas ainda houve alta incidência de TB pós-transplante, possivelmente relacionada a outras formas de infecção, como nova exposição e transmissão pelos doadores.

Application of T-SPOT.TB in pediatric tuberculosis and advances of T-SPOT.TB in other body fluids except blood / 国际儿科学杂志

As a new immunoassay,T-SPOT.TB has been widely used in the diagnosis of tuberculosis in children.A large number of clinical trials show that it has better sensitivity and specificity simultaneously,compared with other diagnostic methods for tuberculosis in children.This article focuses on the principle,influence factors and specific applieation,and reviews advances in other body fluids except blood of T-SPOT.TB.

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

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.

Comparison of Interferon-γ Release Assays and the Tuberculin Skin Test for Diagnosis of Tuberculosis in Human Immunodeficiency Virus: A Systematic Review / 결핵

BACKGROUND: It remains uncertain if interferon-γ release assays (IGRAs) are superior to the tuberculin skin test (TST) for the diagnosis of active tuberculosis (TB) or latent tuberculosis infection (LTBI) in immunosuppressed populations including people with human immunodeficiency virus (HIV) infection. The purpose of this study was to systematically review the performance of IGRAs and the TST in people with HIV with active TB or LTBI in low and high prevalence TB countries. METHODS: We searched the MEDLINE database from 1966 through to January 2017 for studies that compared results of the TST with either the commercial QuantiFERON-TB Gold in Tube (QFTGT) assay or previous assay versions, the T-SPOT.TB assay or in-house IGRAs. Data were summarized by TB prevalence. Tests for concordance and differences in proportions were undertaken as appropriate. The variation in study methodology was appraised. RESULTS: Thirty-two studies including 4,856 HIV subjects met the search criteria. Fourteen studies compared the tests in subjects with LTBI in low TB prevalence settings. The QFTGT had a similar rate of reactivity to the TST, although the first-generation version of that assay was reactive more commonly. IGRAs were more frequently positive than the TST in HIV infected subjects with active TB. There was considerable study methodology and population heterogeneity, and generally low concordance between tests. Both the TST and IGRAs were affected by CD4 T-cell immunodeficiency. CONCLUSION: Our review of comparative data does not provide robust evidence to support the assertion that the IGRAs are superior to the TST when used in HIV infected subjects to diagnose either active TB or LTBI.

Interferon Gamma Release Assays from T Lymphocytes in Patients with Tuberculosis Infection / 现代检验医学杂志

Objective To explore the application value of interferon gamma release assay (IGRAs)in the clinical detection of tuberculosis infected T lymphocytes.Methods Used IGRAs method to detect the 11 968 outpatients and hospitalized pa-tients from 2013 to 2016 with tuberculosis screening.According to the distribution department analysis,also of positive case detection according to age and gender were analysis and comparison and analysis on the uncertainty of results,different methods were compared.Results Among the 11 968 cases,2 048 cases were positive,the positive rate was 17.11%,and the uncertain result was 107 cases,which accounted for 0.89% of the total number.The positive rates from 2013 to 2016 were 19.65%,21.35%,15.82% and 13.56%,respectively.In the detection and screening of pulmonary and pulmonary tuberculo-sis,the positive rates of the department of respiration,the digestive department,the oncology department,the department of neurology and the department of gynecology were 22.07%,20.27%,23.38%,12.84% and 11.86%,respectively.In the positive screening,men accounted for 62.11%,women accounted for 37.89%,men were significantly higher than women.By age group,was less than or equal to 15,16~25,26~45,46~65,was more than orequal to 66 years old,positive rate were 1.96%,18.51%,16.54%,21.25% and 25.73%,respectively.Analysis of uncertain outcome data,department of respira-tion,rheumatism,department of hematology,accounted for 1.99% and 2.35%,respectively.Compared with other laboratory methods,the IGRAs method had obvious advantages.Conclusion Tuberculosis occurs in various body organs,there were differences in gender and age of Mycobacterium tuberculosis infection.IGRAs is a sensitive and specific method for rapid de-tection of Mycobacterium tuberculosis infection,although it can not be used as a diagnostic indicator,but in patients with suspected tuberculosis IGRAs has a larger clinical application value for the further diagnosis of disease.

Clinical Applications of Interferon-gamma Release Assays

Mycobacterium tuberculosis infection remains an important problem in Korea and globally. Interferon-gamma release assays (IGRAs) are blood-based tests that measure the amount of interferon-gamma released by T lymphocytes after stimulation by antigens specific for M. tuberculosis. IGRAs are not recommended for diagnosis of active pulmonary tuberculosis because they cannot distinguish between latent tuberculosis infection (LTBI) and the active disease. For extrapulmonary tuberculosis, IGRAs are considered adjuvant diagnostic tools. The diagnostic performance of IGRAs differs according to infection site. The sensitivity of IGRAs in children is suboptimal in low- and middle-income countries. In Korea, for children who have received a M. bovis bacille Calmette-Guerin (BCG) vaccine after 1 yr of age or have been inoculated with the BCG vaccine twice or more, IGRA is recommended instead of the tuberculin skin test (TST). Diagnosis and treatment of LTBI before the initiation of anti-tumor necrosis factor (TNF) agents are recommended in patients with immune-mediated inflammatory diseases because anti-TNF therapy is associated with an increased risk of developing tuberculosis. A strategy using both TST and IGRA is used for immunocompromised adults in Korea; positive results obtained by either test confirm a diagnosis of LTBI. Negative results of only TST are not considered conclusively negative for LTBI. In addition to interferon-gamma, a biomarker to discriminate between active and latent tuberculosis is required, and IP-10 and IL-2 are currently being investigated in this regard. The use of IGRA would improve the diagnosis of extrapulmonary tuberculosis and LTBI.

Mal de Pott y diagnóstico inmunológico de tuberculosis, a propósito de un caso pediátrico / Pott's disease and immunological diagnosis of tuberculosis, about a pediatric clinical case

Tuberculosis (TB) remains a major health problem in the world. The clinical forms of TB in children are variable, pulmonary involvement occurs in two thirds of cases. In the remaining third, clinical forms incluye node, meningeal and osteoarticular involvement. Case report: 7 year old boy with a history of an osteolytic lesion of the right ischial branch. Three months later he presented with spondylodiscitis at L2-L3, associated with a large abscess in the right iliac psoas muscle. Pott's disease was suspected, and tuberculin test and T-SPOT®.TB test were performed, with a positive result. Antimicrobial treatment was initiated with isoniazid, rifampicin, pyrazinamide and ethambutol. After 30 days, Mycobacterium tuberculosis was isolated from psoas abscess. We discuss methods of TB diagnosis, with special emphasis on immunological methods: tuberculin test and interferon-gamma release assays. Methods of immunological TB diagnosis are an important contribution to the diagnosis of this disease, allowing early initiation of treatment.

La tuberculosis sigue siendo un importante problema en salud en el mundo. Las formas clínicas de TBC en los niños son muy variadas, presentándose en dos tercios de los casos compromiso pulmonar. En el tercio restante destacan los compromisos ganglionar, meníngeo y osteoarticular. Caso clínico: varón de 7 años que presentó una espondilodiscitis L2-L3, asociada a un absceso en músculo psoas-ilíaco derecho. Por sospecha de mal de Pott se realizó PPD y T-SPOT®.TB que resultaron positivos. Se inició tratamiento antimicrobiano asociado con isoniazida, rifampicina, pirazinamida y etambutol. Después de 30 días, se aisló Mycobacterium tuberculosis del absceso del psoas. Se discute los métodos de diagnóstico de TBC en pediatría, con especial énfasis en los métodos inmunológicos: reacción de tuberculina y test de liberación de interferón-gamma, los que son una importante contribución para el diagnóstico de esta enfermedad, permitiendo el pronto inicio de su tratamiento.

The value of interferon gamma release assays in the diagnosis of tuberculous meningitis in children / 临床儿科杂志

ObjectiveTo investigate the diagnostic value of interferon gamma release assays (IGRAs) in children with tuberculous meningitis.MethodsThe prospective case-control study was applied. From January 2012 to March 2013, 32 children diagnosed with tuberculous meningitis (TBM group) and 30 children diagnosed with non-tuberculous meningitis (non-TBM group) were recruited. The positive rates of the interferon gamma release assays (IGRAs), tuberculin skin test (TST), mycobacterium tuberculosis antibody test (TB-IgG), cerebrospinal lfuid of mycobacterium tuberculosis DNA test (TB-DNA), and the sensitivity, speciifcity, negative and positive predictive value of all these tests were compared between TBM group and non-TBM group.Results The positive rate of IGRAs, TST, TB-IgG, and TB-DNA was 87.50%, 56.25%, 46.88% and 34.38%respectively in TBM group, and 6.67%, 23.33%, 20% and 0% respectively in non-TBM group. The differences were statistically signiifcant (P<0.05). The sensitivity of IGRAs, TST, TB-IgG, and TB-DNA was 87.5%, 56.25%, 6.88% and 34.38% respectively. The speciifcity of IGRAs, TST, TB-IgG, and TB-DNA was 93.33%, 76.67%, 80.00% and 100% respectively. The differences of sensitivity and speciifcity were statistically signiifcant (P<0.05). The sensitivity of IGRAs was higher than that of other tests (P<0.017). The positive predictive value of IGRAs, TST, TB-IgG, and TB-DNA was 93.33%, 72%, 71.43% and 100% respec-tively. The negative predictive value was 87.50%, 62.16%, 58.54% and 58.82% respectively.Conclusions IGRAs, TST, TB-IgG, and TB-DNA are valuable in the diagnosis of tuberculous meningitis. IGRAs has a relatively higher sensitivity and speciifcity.

Clinical application of interferon gamma release assays for diagnosis of latent tuberculosis infection in children / 中国生化药物杂志

Objective To explore the clinical value of interferon gamma release assays in early childhood diagnosis of latent tuberculosis infection.Methods 33 patients with suspected latent tuberculosis infection and 35 patients with active tuberculosis infection in our hospital from January 2012 to March 2013 were selected.During the same period selected 30 healthy children as a control group.Respectively were given sputum smear analysis,tuberculin skin test (TST)and vinterferon release assay (IGRA).Compare the positive rate of different methods. Results In suspected latent tuberculosis group,IGRA test results were significantly higher than TST and sputum smear method(P<0.05);in active tuberculosis infection group, IGRA test results were significantly higher than TST and sputum smear(P<0.05 );in healthy control group,TST test results were higher than the IGRA,it is because of patients had been vaccinated with BCG.Conclusion IGRA can be used as one way to diagnosis the latent tuberculosis infection.

Clinical application of interferon gamma release assays for diagnosis of latent tuberculosis infection in children / 临床儿科杂志

Latent tuberculosis infection (LTBI) is defined as a patient is infected with Mycobacterium tuberculosis, without signs and symptoms or radiographic evidence of tuberculosis (TB). Until recently, the only test to identify latent tuberculosis infection was the tuberculin skin test (TST). But in BCG-vaceinated or non-mycobacterium tuberculosis infected individuals TST may be false positive and some babies or immunocompromised individuals have negative results on TST even they were proved to be with TB disease. So it is in need of a new method with higher sensitivity and specificity to diagnose LTBi. More recently, a new diagnostic method of interferon gamma release assays (IGRA) was paid close attention, and in some countries it replaced TST and became the final diagnostic method of LTBI. IGRA has high specificity for Mycobacterium tuberculosis without being influenced by BCG vaccinated or non-mycobacterium tuberculosis infection. In people with normal immune systems, the sensitivity of IGRA is same as TST for TB disease, and in immunocompromised individuals the sensitivity of IGRA is higher than TST. IGRA will have important application in diagnosis of LTBI although it cannot absolutely take the place of TST.