Study protocol: diagnostic accuracy study comparing Cy-Tb and STANDARD F TB-Feron FIA tests for tuberculosis infection diagnosis in Vietnam.

INTRODUCTION: The large reservoir of tuberculosis (TB) infections is one of the main reasons for the persistent incidence of TB. Accurate diagnostic tests are crucial to correctly identify and treat people with TB infection, which is vital to eliminate TB globally. The rdESAT-6 and rCFP-10 (Cy-Tb) injection ('Cy-Tb'), a TB-specific antigen skin test and STANDARD F TB-Feron FIA ('Standard F TB') measuring interferon-gamma by fluorescence immunoassay assay are two novel tools for the diagnosis of TB infection which offer advantages compared with current tests in low-resource settings and reduced costs to both health systems and TB-affected people. The proposed study aims to evaluate the diagnostic accuracy of these two new tests for TB infection diagnosis. METHODS AND ANALYSIS: This cross-sectional study aims to assess the diagnostic accuracy for TB infection of the Cy-Tb skin test and Standard F TB assay (investigational tests) compared with the QuantiFERON-TB Gold Plus (QFT-Plus) assay as the immunological reference standard. Three different cohorts of study participants will be recruited at the Vietnam National Lung Hospital: adults with bacteriologically confirmed pulmonary TB (n=100), household contacts of people with TB (n=200) and people without TB infection (n=50). All consenting participants will undergo simultaneous testing with Cy-Tb, Standard F TB and QFT-Plus. The primary endpoint is the diagnostic accuracy of the Cy-Tb skin test and Standard F TB assay, expressed as sensitivity and specificity against the reference standard. ETHICS AND DISSEMINATION: Ethical approval was granted by the Vietnam National Lung Hospital Institutional Review Board (65/23/CN-HDDD-BVPTU) and the Swedish Ethical Review Authority (Dnr 2023-04271-01). Study results will be disseminated to the scientific community and policymakers through scientific publications. TRIAL REGISTRATION NUMBER: NCT06221735.

Interferon-Gamma Release Assay Combined with Renal Indicators to Reduce the False-Negativity of Latent Tuberculosis Infection in End-Stage Renal Disease with Hemodialysis Patients.

BACKGROUND: Tuberculosis (TB) is still the main cause of mortality due to a single transfectant, Mycobacterium tuberculosis (MTB). Latent tuberculosis infection (LTBI) is a condition characterized by the presence of tuberculosis (TB) that is not clinically apparent but nonetheless shows a sustained response to MTB. Presently, tuberculin skin test (TST) and interferon gamma (IFN-γ) release assays (IGRAs) are mainly used to detect LTBI via cell-mediated immunity of T-cells. For people with end-stage renal disease (ESRD), the diagnosis of patients infected with MTB is difficult because of T-cell dysfunction. To get more accurate diagnosis results of LTBI, it must compensate for the deficiency of IGRA tests. METHODS: Sixty-seven hemodialysis (HD) patients and 96 non-HD patients were enrolled in this study and the study population is continuously included. IFN-γ levels were measured by the QuantiFERON-TB Gold In-Tube (QFT-GIT) test. Kidney function indicators, blood urea nitrogen (BUN), serum creatinine (Cr), and estimated glomerular filtration rate (eGFR) were used to compensate for the declined IFN-γ levels in the IGRA test. RESULTS: In individuals who were previously undetected, the results of compensation with serum Cr increased by 10.81%, allowing for about 28% more detection, and compensation with eGFR increased by 5.41%, allowing for approximately 14% more detectable potential among them and employing both of them could enhance the prior shortcomings of IGRA tests. when both are used, the maximum compensation results show a sensitivity increase rate of 8.81%, and approximately 23% of patients who were previously undetectable may be found. CONCLUSION: Therefore, the renal function markers which are routine tests for HD patients to compensate for the deficiency of IGRA tests could increase the accuracy of LTBI diagnosis.

Diagnostic accuracy of the Enferplex Bovine TB antibody test using individual milk samples from cattle.

Bovine tuberculosis is usually diagnosed using tuberculin skin tests or at post-mortem. Recently, we have developed a serological test for bovine tuberculosis in cattle which shows a high degree of accuracy using serum samples. Here, we have assessed the performance of the test using individual bovine milk samples. The diagnostic specificity estimate using the high sensitivity setting of the test was 99.7% (95% CI: 99.2-99.9). This estimate was not altered significantly by tuberculin boosting. The relative sensitivity estimates of the test using the high sensitivity setting in milk samples from comparative skin test positive animals was 90.8% (95% CI: 87.1-93.6) with boosting. In animals with lesions, the relative sensitivity was 96.0% (95% CI: 89.6-98.7). Analysis of paired serum and milk samples from skin test positive animals showed correlation coefficients ranging from 0.756-0.955 for individual antigens used in the test. Kappa analysis indicated almost perfect agreement between serum and milk results, while McNemar marginal homogeneity analysis showed no statistically significant differences between the two media. The positive and negative likelihood ratio were 347.8 (95% CI: 112.3-1077.5) and 0.092 (95% CI: 0.07-0.13) respectively for boosted samples from skin test positive animals. The results show that the test has high sensitivity and specificity in individual milk samples and thus milk samples could be used for the diagnosis of bovine tuberculosis.

Prevalence estimates of tuberculosis infection in adults in Denmark: a retrospective nationwide register-based cross-sectional study, 2010 to 2018.

BackgroundTuberculosis (TB) elimination requires identifying and treating persons with TB infection (TBI).AimWe estimate the prevalence of positive interferon gamma release assay (IGRA) tests (including TB) and TBI (excluding TB) in Denmark based on TBI screening data from patients with inflammatory bowel disease (IBD) or inflammatory rheumatic disease (IRD).MethodsUsing nationwide Danish registries, we included all patients with IBD or IRD with an IGRA test performed between 2010 and 2018. We estimated the prevalence of TBI and positive IGRA with 95% confidence intervals (CI) in adolescents and adults aged 15-64 years after sample weighting adjusting for distortions in the sample from the background population of Denmark for sex, age group and TB incidence rates (IR) in country of birth.ResultsIn 13,574 patients with IBD or IRD, 12,892 IGRA tests (95.0%) were negative, 461 (3.4%) were positive and 221 (1.6%) were indeterminate, resulting in a weighted TBI prevalence of 3.2% (95% CI: 2.9-3.5) and weighted positive IGRA prevalence of 3.8% (95% CI: 3.5-4.2) among adults aged 15-64 years in the background population of Denmark. Unweighted TBI prevalence increased with age and birthplace in countries with a TB IR higher than 10/100,000 population.ConclusionEstimated TBI prevalence is low in Denmark. We estimate that 200,000 persons have TBI and thus are at risk of developing TB. Screening for TBI and preventive treatment, especially in persons born in high TB incidence countries or immunosuppressed, are crucial to reduce the risk of and eliminate TB.

Is the new tuberculous antigen-based skin test ready for use as an alternative to tuberculin skin test/interferon-gamma release assay for tuberculous diagnosis? A narrative review.

In recent years, novel specific Mycobacteria tuberculous (TB) antigen-based skin test (TBST) has become available for clinical use. The mechanism of TBST is similar to the interferon-gamma release assay (IGRA), making it a potential alternative for identifying latent tuberculous infection (LTBI), especially in subjects with history of bacille Calmette-Guérin vaccination. Three different commercial brands have been developed in Denmark, Russia, and China. Clinical studies in the respective countries have shown promising sensitivity, specificity, and safety profile. Some studies attempted to address the applicability of TBST in specific subject groups but the discrepancy in defining LTBI and problematic methodologies undermine the generalisation of the results to other communities across the world. Limited cost-effectiveness studies for TBST have been conducted without exploring the health economics for preventing development of LTBI into active TB. Unlike IGRA, no clinical studies have addressed the correlation of TBST results (magnitude of induration) with the likelihood of development of active TB. Moreover, the different TBSTs are not widely available for clinical use. While TBST is a promising test to overcome the shortcomings of tuberculin skin tests, more clinical data are needed to support its general application globally for the diagnosis of LTBI.

Screening for latent tuberculosis in migrants-status quo and future challenges.

OBJECTIVES: To review the evidence that migrants from tuberculosis (TB) high-incidence countries migrating to TB low-incidence countries significantly contribute to active TB cases in the counties of destination, primarily through reactivation of latent TB. METHODS: This is a narrative review. The different screening programs in the countries of destination are reviewed either based on screening and preventive treatment of latent TB pre or more commonly - post arrival. RESULTS: Screening can be performed using interferon-gamma release assays (IGRA) or tuberculin skin tests (TST). Preventive treatment of latent TB is using either monotherapy with isoniazid, or in combination with rifampicin or rifapentine. We discuss the ethical issues of preventive treatment in asymptomatic individuals and how these are addressed in different screening programs. CONCLUSION: Screening migrants from TB high endemic countries to TB low endemic countries is beneficial. There is a lack of standardization and agreement on screening protocols, follow up and treatment.

What is New in the Diagnosis of Childhood Tuberculosis?

The fact that almost half of the 1 million cases of childhood tuberculosis (TB) globally remain undiagnosed jeopardizes the TB elimination goal. Fortunately, there are new advances in this field which have the potential to bridge this diagnostic gap. Advances in imaging include computer assisted interpretation of chest X-rays (CXRs), point of care ultrasound (POCUS) and faster and superior computed tomography/ magnetic resonance imaging (CT/ MRI) protocols. The urine lipoarabinomannan test has proved to be a good point of care test for diagnosing TB in Human immunodeficiency virus (HIV) infected children. Stool and nasopharyngeal aspirates are emerging as acceptable alternatives for gastric lavage and induced sputum for diagnosing intrathoracic tuberculosis. Xpert MTB/RIF Ultra has improved sensitivity compared to Xpert MTB/RIF for diagnosing both pulmonary/ extrapulmonary TB. Xpert XDR is another commercially available accurate point of care test for detecting resistance to drugs other than rifampicin in smear positive samples. Other molecular methods including new line probe assays, pyrosequencing, whole genome sequencing, and targeted next generation sequencing are extremely promising but not available commercially at present. The C-Tb skin test is an acceptable alternative to the tuberculin skin test and interferon gamma release assays for diagnosis of latent infection. There is an urgent need to incorporate some of these advances in the existing diagnostic algorithms of childhood TB.

Cost-Effectiveness Analysis Comparing QuantiFERON-TB Gold Plus Test and Tuberculin Skin Test for the Diagnosis of Latent Tuberculosis Infection in Immunocompetent Subjects in Colombia.

OBJECTIVES: To determine the cost-effectiveness of the QuantiFERON-TB Gold Plus (QFT-Plus) test versus the tuberculin skin test in diagnosing latent tuberculosis infection in immunocompetent subjects in the context of the Colombian healthcare system. METHODS: A hypothetical cohort of 2000 immunocompetent adults vaccinated with Bacillus Calmette-Guérin at birth who are asymptomatic for tuberculosis disease was simulated and included in a decision tree over a horizon of <1 year. The direct healthcare costs related to tests, antituberculosis treatment, and medical care were considered, and diagnostic performance was used as a measure of effectiveness. The incremental cost-effectiveness ratio (ICER) was estimated, and univariate deterministic and probabilistic sensitivity analyses were carried out using 5000 simulations. The currency was the US dollar for the year 2022, with a cost-effectiveness threshold of $6666 USD (1 gross domestic product per capita for 2022). RESULTS: QFT-Plus was cost-effective with an ICER of $5687 USD for each correctly diagnosed case relative to a threshold of $6666 USD. In the deterministic analysis, QFT-Plus was cost-effective in half of the proposed scenarios. The variable that most affected the ICER was the prevalence of latent tuberculosis and test sensitivities. In the probabilistic analysis, QFT-Plus was cost-effective in 54.74% of the simulated scenarios, and tuberculin skin test was dominant in 13.84%. CONCLUSIONS: The study provides evidence of the cost-effectiveness of QFT-Plus compared with the tuberculin skin test in diagnosing latent tuberculosis infection in immunocompetent adults in the Colombian context.

Assessment of the diagnostic performance of intradermal tuberculin test and post-mortem inspection for the diagnosis of bovine tuberculosis according to WOAH guidelines.

Bovine tuberculosis (bTB) constitutes a global challenge for public and animal health with still some deficiencies regarding its diagnosis. This study aimed to estimate the accuracy of the single intradermal tuberculin test (SIT) and post-mortem inspection for different diagnostic objectives following WOAH guidelines. Tissue samples from 59 microbiological culture/PCR-positive and 58 microbiological culture/PCR-negative cattle were evaluated. The diagnostic sensitivity and specificity, the positive and negative probability indices as well as the positive and negative predictive values (PPV and NPV) of each technique were estimated for different pretest probabilities. The SIT with strict interpretation demonstrated moderate precision in confirming the absence of infection in populations historically free of bTB, with a 12.1% rate of false positives, but also detecting positive animals in the early stage of the eradication programs, with a 13.6% rate of false negatives. The diagnostic performance for ruling out bTB was notably high (NPV > 90%) in animals with a pre-test probability (PTP) below 42%. Post-mortem inspection constituted an interesting alternative tool to confirm suspected and positive cases for SIT, particularly in areas with bTB prevalence exceeding 19%, where implementing SIT and eradication measures may be impractical. In these areas, the likelihood that animals with tuberculosis-like lesions are affected by the disease surpasses 90%. Similarly, in herds with a PTP below 25%, the absence of bTB could be confidently ruled out with over 90% certainty. These findings highlight the effectiveness of SIT and post-mortem inspection as valuable techniques for current eradication programs and controlling bTB in high-prevalence areas where molecular techniques may not be feasible.

QuantiFERON Gold-In-Tube for the diagnosis of mycobacterial tuberculosis infection in children under 5 years of age: A systematic review and meta-analysis.

BACKGROUND: Previous meta-analysis regarding the performance of QuantiFERON Gold-In-Tube in children have yielded contrasting results. Emerging data in children younger than 5 years of age necessitates a new analysis. METHODS: Systematic searches were conducted of MedLINE, EMBASE and Cochrane databases between 1998-2023. Pooled estimates of sensitivities and specificities of QFT-GIT compared to tuberculin skin test (TST) were calculated. The Kappa (k) coefficient was calculated for each study to determine the degree of congruence between TST and QFT-GIT results. Studies including patients co-infected with HIV or other immune compromising conditions or those treated with anti-tubercular treatment were excluded. RESULTS: Seventeen studies (4335 patients) were included in quantitative analysis. All studies were conducted in middle to high income countries. They were conducted across 14 countries and 4 studies in countries with high TB incidence. The pooled sensitivity, specificity and DOR were 0.45 (0.42-0.48), 0.96 (0.96-0.97) and 18.84 (7.33-48.41) respectively. The ability of QFT-GIT to discriminate with disease and no disease was "good" as demonstrated by a summary receiver operating characteristic curve with area under curve of 0.7812. The average Kappa (k) co-efficient was 0.501 with a wide variety of values between studies (0.167 to 0.800). CONCLUSION: The findings of this meta-analysis support the judicious use of QFT-GIT in children 5 years and under, with caution as a sole test to exclude Tuberculosis in this age group. The heterogeneity and methodological quality of diagnostic studies limits the generalisability of results.

Tuberculosis and childhood cancer - A review of literature.

Tuberculosis and malignancy are major public health problems in developing countries like India and causes significant morbidity and mortality. Mycobacterium tuberculosis is an aerobic acid-fast bacilli which is an important pathogen especially complicating clinical status of paediatric oncology patients and treatment of infection with this bacilli is challenging in this subpopulation of patients because of ongoing immunosuppression and relative lack of published guidelines. Atypical presentations of tuberculosis in children also complicate the diagnosis and management. All the more, in tuberculosis endemic area lung cancer may be mistakenly diagnosed as tuberculosis or vice versa and this wrong diagnosis increases the burden on country's health status. It is noted that tuberculosis prevalence is high in children with haematological malignancy and head and neck tumours compared to other solid organ tumours. Moreover, it is found that morbidity and mortality from tuberculosis is more in children from WHO listed high TB burden countries who undergo hematopoietic stem cell and solid organ transplantation. Use of immune checkpoint inhibitors as novel therapy in treatment of childhood malignancies has led to modification of the body's immunological response and has resulted in increased latent tuberculosis infection reactivation as one immune-related infectious consequence. Latent TB infection screening is important concept in management of paediatric oncology patients. Currently, the tests employed as screening diagnostics for LTBI are interferon-gamma release assay (IGRA) blood test and the tuberculin skin test (TST). Various regimens have been suggested for the treatment of LTBI. But, after a positive IGRA or TST and prior to latent TB treatment, active tuberculosis should be ruled out by detailed history taking, examination and appropriate investigations so as to minimize the risk of drug resistance with anti-tuberculosis monotherapy used in LTBI treatment. To add on to literature, Non tuberculous mycobacteria are universally present environmental organisms. However, in immunocompromised children especially in subpopulation of malignancy, NTM is known to cause infections which needs protocol based management. Also importance has to given to implementation of adequate preventive and corrective measures to prevent such opportunistic infection in paediatric oncology subpopulation. In this review, we provide an overview of tuberculosis in paediatric oncology patients and summarize the expansive body of literature on the tuberculosis mimicking carcinoma, tuberculosis burden in transplantation patients and those receiving immune check point inhibitors, latent TB infection screening and management, and NTM infection in children with malignancy.

Interferon-gamma release assay for the diagnosis of latent tuberculosis infection in the prison population with a positive tuberculin test: a descriptive study in a prison (Burgos, Spain).

OBJECTIVES: A high prevalence of prison inmates have a positive tuberculin skin test (TST) and sometimes unnecessary treatment for latent tuberculosis infection (LTBI) is prescribed. The prison tuberculosis prevention and control program has not generalized the use of QuantiFERON (QFT) in prisons. We set out to describe the implementation and usefulness of QFT in a population of inmates with positive TST, and to detect false positives and avoid unnecessary treatments. We also analysed the sociodemographic variables of the inmate population. MATERIAL AND METHODS: All the positive TST tests between December 2020 and December 2021 from an average population of 300 inmates in Burgos prison were analysed. The QFT value was measured in all the positive cases. Sociodemographic variables were analysed and finally the number of inmates with positive TST, but with a negative QFT result and therefore not requiring LTBI treatment, was evaluated. RESULTS: A total of 41 inmates were included in the study, with a mean age of 44 years. The proportion between Spanish inmates and foreigners was similar. Of all the positive TST, 48.8% were QFT negative. DISCUSSION: It was observed that QFT is a safe method for the diagnosis of LTBI in prisons and that its use would contribute to a more specific selection of inmates who actually need chemoprophylactic treatment for LTBI.

How useful is the tuberculin skin test for tuberculosis detection: Assessing diagnostic accuracy metrics through a large Tunisian case-control study.

Background and aim: During the past decade, the frequency of extrapulmonary forms of tuberculosis (TB) has increased. These forms are often miss-diagnosed. This statement of the TB epidemiological profile modification, conduct us to reflect about the utility of the Tuberculin Skin Test (TST) in active TB detection. This study aimed to evaluate the diagnostic accuracy performance of the TST for active tuberculosis detection. Methods: This was a case-control, multicenter study conducted in 11 anti-TB centers in Tunisia (June-November2014). The cases were adults aged between 18 and 55 years with newly diagnosed and confirmed tuberculosis. Controls were free from tuberculosis. A data collection sheet was filled out and a TST was performed for each participant.Diagnostic accuracy measures of TST were estimated using Receiver Operating Curve (ROC) curve and Area Under Curve (AUC) to estimate sensitivity and specificity of a determined cut-off point. Results: Overall, 1050 patients were enrolled, composed of 336 cases and 714 controls. The mean age was 38.3±11.8 years for cases and 33.6±11 years for controls.The mean diameter of the TST induration was significantly higher among cases than controls (13.7mm vs.6.2mm; p=10 -6). AUC was 0.789 [95% CI: 0.758-0.819; p=0.01], corresponding to a moderate discriminating performance for this test. The most discriminative cut-off value of the TST, which was associated with the best sensitivity (73.7%) and specificity (76.6%) couple was   ≥ 11 mm with a Youden index of 0.503. Positive and Negative predictive values were 3.11% and 99.52%, respectively. Conclusions: TST could be a useful tool used for active tuberculosis detection, with a moderate global performance and accepted sensitivity and specificity at the cut-off point of 11 mm. However, it cannot be considered as a gold standard test due to its multiple disadvantages.

Conversión de prueba cutánea de derivado proteico purificado durante el tratamiento con anti-TNF / Skin test conversion of purified protein derivative during treatment with anti-TNF

Introducción: los anti-TNF-α se asocian con mayor riesgo de desarrollar tuberculosis (TB). La prueba del derivado proteico purificado (purified protein derivative, PPD) se emplea para diagnosticar infección de tuberculosis latente (ITL). Se recomienda el cribado para TB previo al inicio de terapia anti-TNF-α y el seguimiento para evaluar la posible conversión de la PPD durante el tratamiento. El tratamiento de la ITL puede reducir el riesgo de desarrollar enfermedad activa en un 90%. Objetivos: actualmente los resultados de conversión de la PPD y su interpretación durante el tratamiento anti-TNF-α son variables, por tal motivo nos propusimos conocer la frecuencia de conversión de la PPD en este grupo de pacientes de nuestro medio. Materiales y métodos: realizamos un estudio descriptivo, observacional y retrospectivo que incluyó pacientes >18 años, diagnosticados con enfermedad reumática, tratados con anti-TNF-α. Resultados: se incluyeron 54 pacientes (46,7 ± a 12 años), de los cuales 36, presentaron diagnóstico de artritis reumatoidea, seis de artritis idiopática juvenil, cinco de espondilitis anquilosante, tres de artritis psoriásica, tres de uveítis y uno de queratitis intersticial. Los tratamientos fueron: 30 adalimumab, 17 certolizumab, siete etanercept, 44 metotrexato, 19 leflunomida, nueve hidroxicloroquina, dos sulfasalazina, dos azatioprina, uno mofetil micofenolato y glucocorticoides (28 de 54); la conversión de la PPD ocurrió en un solo paciente. Conclusiones: en el presente trabajo la seroconversión fue baja en contraste con otras series. La prueba de PPD es un método accesible, ampliamente disponible, adecuado y sensible para diagnosticar ITL.

Introduction: anti-TNF-α are associated with an increased risk of developing tuberculosis (TB). Purified protein derivative (PPD) is used to demonstrate a latent TB infection (LTBI). Screening is recommended for TB prior to the onset of anti-TNF-α and monitoring evaluating possible conversion of PPD during treatment. Treatment of LTBI can reduce the risk of active disease development by up to 90%. Objectives: currently the results of PPD conversion and its interpretation during anti-TNF-α treatment are variable and that is why we set out to know the frequency of conversion of PPD in this group of patients in our environment. Materials and methods: a descriptive, analytical, observational, retrospective study was conducted. Including patients >18 years old, diagnosed with rheumatic disease, treated with anti-TNF-α. Results: 54 patients were included (46.7 ± to 12 years), of which 36 presented a diagnosis of rheumatoid arthritis, 6 juvenile idiopathic arthritis, 5 ankylosing spondylitis, 3 psoriatic arthritis, 3 uveitis, 1 interstitial keratitis. The treatments were: 30 adalimumab, 17 certolizumab, 7 etanercept, 44 methotrexate, 19 leflunomide, 9 hydroxychloroquine, 2 sulfasalazine, 2 azathioprine, 1 mycophenolate mofetil and glucocorticoids (28/54). PPD conversion took place in 1 patient. Conclusions: in the present study, seroconversion was low in contrast to other series. The PPD test is an accessible, widely available, adequate and sensitive method for diagnosing LTBI, which the rheumatologist should use in his daily practice.

Seguimiento de los contactos de casos de tuberculosis / Follow-up of Contacts of Tuberculosis Cases

Introducción: La tuberculosis constituye la principal causa de muerte en el mundo por enfermedad infecciosa. Objetivo: Verificar el cumplimiento de las acciones de control de foco de los contactos de casos de tuberculosis. Métodos: Estudio descriptivo, transversal. Universo constituido por los 338 contactos identificados de 10 casos de tuberculosis. Los datos procedieron de encuestas epidemiológicas, base de datos de morbilidad y tarjetas de notificación de la unidad municipal de higiene y epidemiologia del municipio Boyeros. Se utilizaron las variables: edad, sexo, nivel educacional y ocupación. Se identificaron los factores de vulnerabilidad en los contactos y se verificó cumplimiento del examen médico, los complementarios, realización y resultado de prueba de tuberculina, quimioprofilaxis y seguimiento. Resultados: Prevaleció el sexo masculino (64,2 por ciento) y los mayores de 65 años (46,7 por ciento). Los grupos vulnerables más frecuentes fueron los contactos en unidades de salud con internamiento prolongado y más de 60 años (87,2 por ciento y 62,1 por ciento, respectivamente). No se detectó el número real de contactos y convivientes ni fue investigado el 100 por ciento. Las pruebas de tuberculina realizadas arrojaron el mayor porciento de no reactores, el 90 por ciento de los contactos recibieron quimiprofilaxis y su seguimiento fue deficiente. Conclusiones: La no detección oportuna de los contactos y convivientes de casos de tuberculosis y los incumplimientos de su estudio constituyeron las principales deficiencias de los controles de foco realizados. El seguimiento de los contactos fue inadecuado, lo que pudiera propiciar la aparición de nuevos casos de tuberculosis en el municipio(AU)

Introduction: Tuberculosis is worldwide the main cause of death due to infectious disease. Objective: To verify compliance with outbreak control actions associated with contacts of tuberculosis cases. Methods: Descriptive and cross-sectional study. The universe was made up of the 338 contacts identified from ten cases of tuberculosis. The data came from epidemiological surveys, morbidity database and notification cards of the municipal hygiene and epidemiology unit of Boyeros Municipality. The following variables were used: age, sex, educational level and occupation. The vulnerability factors in the contacts were identified, as well as compliance with medical examination, complementary tests, performance and result of tuberculin test, chemoprophylaxis and follow-up. Results: The male sex (64.2 percent) and people over 65 years of age (46.7 percent) prevailed. The most frequent vulnerable groups were contacts in health units with prolonged hospitalization and aged over 60 years (87.2 percent and 62.1 percent, respectively). The actual number of contacts and partners was not detected, nor 100 percent of them were investigated. The tuberculin tests carried out showed the highest percentage of non-reactors. 90 percent of the contacts received chemoprophylaxis and their follow-up was poor. Conclusions: There was no timely detection of the contacts and cohabitants of tuberculosis cases and no compliance with their study, which constituted the main deficiencies of the outbreak controls carried out. The follow-up of the contacts was inadequate, which could lead to the appearance of new cases of tuberculosis in the municipality(AU)

Enfermedad tuberculosa en la edad pediátrica: experiencia de diez años / Tuberculous disease in Pediatrics: ten years' experience

Objetivo: describir la tuberculosis infantil de 2005 a 2015 en Navarra, con datos demográficos, clínicos, radiológicos, microbiológicos, tratamiento y evolución. Material y métodos: estudio descriptivo retrospectivo a partir de datos de historia clínica de los pacientes atendidos entre 2005 y 2015. Resultados: 52 pacientes, 57,7% varones, 42,3% mujeres, mediana de edad cuatro años, 38,5% inmigrantes, 61,5% hijos de inmigrantes. Distribución homogénea en los diez años, excepto un brote en 2011. Sintomáticos el 69,2%. En el 63,5% de los pacientes el caso índice es conocido. La forma clínica más frecuente es la pulmonar (82,7%). La radiología fue patológica en el 86,5%, se realizó tomografía computarizada pulmonar en el 82,7% (95,3% patológicos). El 71,2% de los cultivos fueron positivos para Mycobacterium tuberculosis (sensibles 92,3%). Tratamiento con cuatro fármacos y posteriormente dos de 6 a 12 meses. Evolución: 84,6% curación, 13,5% secuelas y un exitus. Conclusiones: la tuberculosis es un problema de salud infantil cuya forma más frecuente es pulmonar. Evoluciona favorablemente, pero presenta morbimortalidad. Es imprescindible tenerla en cuenta para diagnóstico y tratamiento precoz

Objective: to describe tuberculosis in Pediatrics from 2005-2015 in Navarra, attending to demographic, clinic, radiologic, microbiologic, treatment and evolution data. Material and methods: a retrospective descriptive study based on data from the clinical history of patients treated between 2005 and 2015. Results: we studied 52 patients, 57.7% men, 42.3% women, age: 4 years old. 38.5% are immigrant and 61.5% children from immigrants. During the last 10 years, the distribution has been homogeneous, despite of one outbreak in 2011. 69.2% had symptoms when diagnosed. In 63.5% we knew index case. The most frequent clinical form is the pulmonary one. Simple Rx was pathological in 86,5% of cases and CT was applied in 82,7% (being diagnostic in 95'3% of them). 71,2% of microbiological cultures were positive for Mycobacterium tuberculosis (92,3% of them were sensible to M. tuberculosis sensible to standard treatment). All patients were treated with four drugs and then two up to 6-12 months. Follow up: 84.6% healed, 13.5% healed but there were sequelae and one of our patients died. Conclusion: tuberculosis represents a problem in children health. Pulmonary tuberculosis is the most frequent clinical form. Normally, it evolves favourably but morbimortality exists. It is essential to consider tuberculosis in order to have an early diagnosis and treatment

La prueba de tuberculina positiva no es sinónimo de tuberculosis latente / The positive tuberculin test is not synonymous with latent tuberculosis

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Diagnosis and treatment of latent tuberculosis infection in patients undergoing treatment with immunobiologic agents: a four-year experience in an endemic area / Impacto do diagnóstico e tratamento de tuberculose latente em pacientes submetidos à terapia imunobiológica: experiência de quatro anos em área endêmica

ABSTRACT Objective: To describe the incidence of active tuberculosis and the occurrence of adverse events after isoniazid treatment in patients with latent tuberculosis infection (LTBI) who also had chronic inflammatory diseases and were treated with immunobiologic agents in an endemic area in Brazil. Methods: The diagnosis of LTBI was based on anamnesis, clinical examination, chest X-ray, and a tuberculin skin test (TST). Patients received prophylactic treatment (isoniazid for six months) in accordance with the Brazilian guidelines. Results: A total of 101 patients were evaluated between July of 2011 and July of 2015. Of those, 55 (54.46%) were women (mean age, 53.16 ± 1.76 years) and 46 (45.54%) were men (mean age, 45.39 ± 2.13 years). A total of 79 patients (78.22%) were being treated with immunobiologic agents and 22 (21.78%) were being treated with immunomodulatory or immunosuppressive agents. In the screening for LTBI, 53 patients (52.48%) had a TST induration ≥ 10 mm. Chest X-ray findings consistent with LTBI were observed in 36 patients (35.64%). Isoniazid preventive therapy was effective in 96 (95.05%) of the 101 patients evaluated. It is of note that 84 (83.17%) of the patients experienced no adverse effects from the use of isoniazid and that 83 (98.81%) of those patients completed the prophylactic treatment (p = 0.002). Active tuberculosis was diagnosed in 5 (6.33%) of the 79 patients treated with immunobiologic agents and in 1 (4.55%) of the 22 patients treated with other immunomodulators/immunosuppressants. Conclusions: A six-month course of isoniazid proved to be safe and effective in the treatment of LTBI, which is essential to reducing the risk of developing active tuberculosis.

RESUMO Objetivo: Descrever a incidência de tuberculose ativa e a ocorrência de eventos adversos do tratamento com isoniazida em pacientes diagnosticados com tuberculose latente (TBL), portadores de doenças inflamatórias crônicas e tratados com agentes imunobiológicos em uma área endêmica no Brasil. Métodos: O diagnóstico de TBL foi feito com base em anamnese, exame clínico, radiografia de tórax e teste tuberculínico (TT). O tratamento profilático foi realizado segundo diretrizes brasileiras com isoniazida por seis meses. Resultados: Foram estudados 101 pacientes entre julho de 2011 e julho de 2015. Desses, 55 (54,46%) eram mulheres (média de idade = 53,16 ± 1,76 anos) e 46 (45,54%) eram homens (média de idade = 45,39 ± 2,13 anos), sendo que 79 (78,22%) foram tratados com agentes imunobiológicos e 22 (21,78%) com outros agentes imunomoduladores ou imunossupressores. Na triagem para TBL, 53 pacientes (52,48%) apresentaram TT ≥ 10 mm. A radiografia de tórax alterada por imagens compatíveis com TBL foi observada em 36 pacientes (35,64%). O tratamento profilático com isoniazida mostrou uma eficácia de 95,05% (96/101). É relevante mencionar que 84 (83,17%) dos pacientes não apresentaram nenhum efeito adverso à isoniazida e, desses, 83 (98,81%) completaram o tratamento profilático (p = 0,002). Tuberculose ativa foi diagnosticada em 5 (6,33%) dos 79 pacientes tratados com agentes imunobiológicos e em 1 (4,55%) dos 22 pacientes tratados com outros imunomoduladores/imunossupressores. Conclusões: O uso de isoniazida por seis meses mostrou-se seguro e eficaz no tratamento da TBL nesses pacientes, o que é essencial para reduzir o risco de desenvolvimento de tuberculose ativa.

Evolución del estudio de la tuberculosis mediante Quantiferon Gold / Advances in the study of tuberculosis using Quantiferon Gold assay

La tuberculosis es una infección causada por especies del complejo Mycobacterium tuberculosis. Representa una de las enfermedades contagiosas causantes de mayor morbimortalidad. Es de declaración obligatoria, y su vigilancia es llevada a cabo por la Red Nacional de Vigilancia Epidemiológica y por el Centro Europeo para la Prevención y Control de Enfermedades (ECDC) y por la Oficina Regional Europea de la OMS. La técnica habitual para el diagnóstico es la prueba de la tuberculina: tras la inyección intradérmica de un derivado proteico purificado (PPD) se desencadena una reacción de hipersensibilidad si el individuo ha estado en contacto con dicha sustancia previamente, pero no es capaz de discernir entre un individuo infectado y un individuo vacunado. Con el fin de proporcionar un diagnóstico más específico y seguro se han desarrollado nuevos métodos diagnósticos basados en la cuantificación in vitro de la respuesta inmune celular, conocidos genéricamente como interferon gamma release assays (IGRA), que detectan la liberación de interferón-gamma por las célulasT sensibilizadas cuando son sometidas a diferentes antígenos micobacterianos. Actualmente los IGRA comercializados para el diagnóstico in vitro de la infección tuberculosa son dos: QuantiFERON-TB Gold In-Tube (Cellestis(R), QIAGEN) y T-SPOT.TB (Oxford Immunotec(R)). Nuestro objetivo es realizar una pequeña revisión sobre el uso del método Quantiferón en el diagnóstico de infección tuberculosa

Tuberculosis is an infection caused by species of the Mycobacterium tuberculosis complex. It is a contagious disease with a high morbidity and mortality. It is mandatory to notify it, and its monitoring is carried out by the National Network for Epidemiological Surveillance, the European Centre for Disease Prevention and Control (ECDC), and the European Regional Office of the WHO. The usual technique for diagnosis is the tuberculin test. This includes the intradermal injection of a purified protein derivative (PPD), which triggers a hypersensitivity reaction if the individual has been in contact with the substance previously. In order to provide a more specific and safe diagnosis, new diagnostic methods have been developed based on the in vitro quantification of the cellular immune response, known generically as 'interferon gamma release assays' (IGRA), which detect the release of interferon-gamma by the sensitised T cells when subjected to different mycobacterial antigens. There are currently two IGRAs being marketed for the in vitro diagnosis of tuberculosis infection QuantiFERON-TB Gold In-Tube (Cellestis(R), QIAGEN) and T-SPOT.TB (Oxford Immunotec(R)). The aim is to present a short review on the use of the Quantiferon method in the diagnosis of tuberculosis infection