Infecção latente pelo Mycobacterium tuberculosis em trabalhadores da saúde na Bahia / Latent Infection by Mycobacterium tuberculosis in health Workers in Bahia, Brazil

Objetivo: Estimar a prevalência de positividade do Teste Tuberculínico (TT) no rastreamento da infecção latente pelo Mycobacterium tuberculosis (ILTB) e identificar fatores associados entre trabalhadores da Atenção Primária à Saúde (APS) e média complexidade no segundo maior município do Estado da Bahia. Métodos: Inquérito epidemiológico, com 370 participantes, que avaliou dados sociodemográficos, ocupacionais, consumo de tabaco, álcool e variáveis relacionadas à tuberculose (TB), no período de abril/2021 a março/2022. Aplicou-se o TT por via intradérmica, com leitura após 72h. Resultados: A prevalência de positividade do TT foi de 41,3% e 17,6% para TT ≥ 5mm e TT ≥ 10mm, respectivamente. Para TT ≥ 5mm, as variáveis associadas foram: possuir cicatriz da vacina Bacilo Calmette-Guérin (BCG) e contato prévio com pessoas com TB. Conclusão: A prevalência de positividade do TT foi elevada entre os participantes do estudo. Fazem-se necessárias medidas de proteção ambiental, coletiva e individual para redução do risco de ILTB.

Objective: To estimate the prevalence of tuberculin test (TT) positivity in screening for Latent Mycobacterium tuberculosis Infection (LTBI) and to identify associated factors in Primary Health Care (PHC) and medium complexity workers in the second largest municipality in the State of Bahia, Brazil. Methods: Epidemiological survey with 370 workers on sociodemographic and occupational data, tobacco and alcohol use and variables related to Tuberculosis (TB), during April 2021 and March 2022. TT was applied intradermally, with reading after 72 hours. Results: The prevalence of positive TT was 41.3% and 17.6% for TT ≥ 5mm and TT ≥ 10mm, respectively. For TT ≥ 5mm, the associated variables were: presence of Bacillus Calmette-Guérin (BCG) vaccine scar and previous contact with TB patients. Conclusion: The prevalence of TST positivity was high among study participants. Environmental, collective and individual protection measures are necessary to reduce the risk of LTBI.

Limited usefulness of the IS6110 touchdown-PCR in blood for tuberculin skin test false-negative cattle with serological response to Mycobacterium bovis.

Ante-mortem diagnosis of bovine tuberculosis (bTB) is based mainly on the tuberculin skin test (TST) and the ɣ-IFN release assay (IGRA). Some infected animals escape screening tests, thus, limit herd sanitation. Previous reports have suggested a predominant pattern of multi-organ lesions attributable to Mycobacterium bovis (the causative agent of bTB) bacteraemia. A case-control study was conducted to investigate blood PCR as an alternative tool for improving ante-mortem detection of TST false-negative bovines. Cases comprised 70 TST false-negative bovines (cases), which were serology positive, and controls included 81 TST positive bovines; all of them confirmed as infected with M. bovis. Detection of the IS6110 target through touchdown blood-PCR (IS6110 TD-PCR) was performed. The positivity of the blood-PCR was 27.2% in the control group. This performance was similar to the 15% obtained among cases (p = 0.134). Most cases identified by the IS6110 TD-PCR exhibited focalized lesions (p = 0.002). Results demonstrated that blood-PCR could detect TST false-negative cattle, even if they are negative for IGRA. Considering that cases exhibited humoral response to M. bovis, further studies conducted in a pre-serological stage could provide evidence about the real contribution of the technique in herds.

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.

Prevalence of positive tuberculin skin test in a Brazilian sample of rheumatoid arthritis and spondylarthritis patients

SUMMARY OBJECTIVE: Patients with rheumatic diseases have an increased risk of infections, especially tuberculosis. In this study, we aimed to recognize the positivity rate of tuberculosis skin test in patients with rheumatoid arthritis and spondyloarthritis and the characteristics of the patients with positive results. METHODS: Retrospective study of tuberculosis skin test results in patients followed from 2004 to 2021 in a single rheumatology unit. Data related to clinical and epidemiological features, along with treatment information referring to the period in which the tuberculosis skin test was performed, were collected from patients' charts. RESULTS: A total of 723 tests were identified (448 tests in 269 rheumatoid arthritis patients and 275 in 174 spondyloarthritis patients). In the rheumatoid arthritis sample, 31/275 (11.5%) individuals had positive tests, and in the spondyloarthritis, 38/174 (21.8%) had positive tests. In the rheumatoid arthritis sample, patients with positive tuberculosis skin tests used a higher dose of methotrexate than those with negative results (median of 25 mg/week versus median of 20 mg/week respectively; p=0.02). In the spondyloarthritis sample, tuberculosis skin test positivity was associated with alcohol ingestion (13.1% versus 2.9% in users and non-users respectively; p=0.02) and sulfasalazine use (15.7% of positivity in users versus 5% in non-users; p=0.01). CONCLUSION: The tuberculosis skin test-positive prevalence in rheumatoid arthritis was lower than in the spondyloarthritis sample. Patients with rheumatoid arthritis using a higher dosage of methotrexate or with spondyloarthritis using sulfasalazine had more frequency of tuberculosis skin test positivity and should be carefully followed by the attending physician in order to avoid the appearance of full-blown tuberculosis.

Incidence, Diagnosis and Treatment of Otorhinolaryngological, Head and Neck Tuberculosis: A Prospective Clinical Study.

Introduction Tuberculosis is a disease of diversified presentation. It affects almost all organs in the body, and otorhinolaryngological, head and neck involvement is not an exception. Objective To increase awareness about the different clinical presentations of otorhinolaryngological, head and neck tuberculosis, the techniques employed to diagnose it, and to assess the response to the treatment. Methods We conducted a prospective study of 114 patients who presented primarily with otorhinolaryngological, head and neck tuberculosis. Routine blood investigations, chest radiographs, the tuberculin test, and sputum examination for the presence of acid-fast bacilli were performed in all cases. Site-specific investigations were performed in relevant cases only. The patients were treated according to the antitubercular treatment (ATT) regimen recommended by the Indian Ministry of Health and Family Welfare's National Tuberculosis Elimination Program (NTEP), and they were followed up clinically two and six months after starting the ATT. Results Tubercular cervical lymphadenopathy was the most common clinical presentation (85.96%), followed by deep neck abscess (5.27%). Fine-needle aspiration cytology proved to be a reliable tool for the diagnosis of tubercular lymphadenopathy. Improvement at the end of 2 and 6 months of the ATT was observed in 90.35% and 96.50% of the cases respectively. Conclusion The diagnosis of otorhinolaryngological, head and neck tuberculosis requires a high index of clinical suspicion, and the ATT proved to be very effective in reducing the severity of the disease.

Prevalence of latent Mycobacterium tuberculosis infection in hematopoietic stem cell transplantation comparing tuberculin skin test and interferon-gamma release assay.

The aim of this study was to evaluate the prevalence of latent Mycobacterium tuberculosis infection in hematopoietic stem cell transplantation candidates, using tuberculin skin test and QuantiFERON-TB Gold-Plus, in a high-burden tuberculosis country. Adult candidates for hematopoietic stem cell transplantation performed both tests before and those submitted to transplantation were followed up for 12 months. The prevalence of latent Mycobacterium tuberculosis infection was 17.1% and a moderate agreement between QuantiFERON-TB Gold-Plus and tuberculin skin test was observed in this population. Previous tuberculosis exposure was a risk factor for latent Mycobacterium tuberculosis infection. No cases of tuberculosis were diagnosed during follow-up period.

Comparison of Two Tuberculosis Infection Tests in a South American Tertiary Hospital: STANDARD F TB-Feron FIA vs. QIAreachTM QuantiFERON-TB.

INTRODUCTION: Tuberculosis (TB) is one of the most prevalent respiratory diseases in the world. In 2020 there were at least 9.9 million new infections, with 1.5 million deaths. Approximately 10% of people infected with Mycobacterium tuberculosis develop the disease during the first 2 to 5 years after infection. In South America, the diagnosis of Latent Tuberculosis Infections (LTBI) continues to be performed through the Mantoux tuberculin skin test (TST). OBJECTIVE: The objective of our study was to compare the sensitivity of a new immunofluorescence IGRA test against a widely available IGRA kit on the market. MATERIAL AND METHOD: Close contact with infectious TB patients, HIV patients, or immunocompromised for another cause were recruited. Two interferon-gamma release assay (IGRA) diagnostic kits were used and compared with TST. RESULTS: 76 patients were recruited, 93.42% were Chilean nationality, and 98.68% of the patients did not have immunosuppression. The sensitivity of the new technique was 88.89%, and the specificity was 92.50% in the study population compared to the IGRA previously used. In the subgroup older than 36 years, the sensitivity was 95.65%, and the specificity was 89.47%. CONCLUSION: IGRA techniques are a new resource in clinical laboratories to make an accurate diagnosis of LTBI in the region of the Americas. In our population, the greatest benefit of this new IGRA would be observed in people over 36 years of age, where the sensitivity of the technique was like that of the currently available test.

Frecuencia de infección tuberculosa latente en estudiantes de Medicina en una universidad privada de Paraguay

Introducción: la infección tuberculosa latente es un estado de respuesta inmune tipo hipersensibilidad celular retardada del organismo a la estimulación por antígenos de Mycobacterium tuberculosis sin evidencia clínica y radiológica de tuberculosis. Puede ser diagnosticada mediante la prueba de tuberculina o derivado proteico purificado de tuberculina. Objetivos: determinar la frecuencia de infección tuberculosa latente en estudiantes de Medicina y las variables asociadas a una reacción positiva en la prueba de tuberculina. Metodología: se realizó un estudio descriptivo de corte transversal, en el cual se procedió a realizar la prueba de tuberculina por el método de Mantoux utilizando 0,1 ml de derivado proteico purificado de tuberculina Tubersol, en estudiantes de la carrera de Medicina de una universidad. Resultados: participaron 290 estudiantes. La frecuencia de infección tuberculosa latente fue 19,3%. Al relacionar las variables demográficas con la reacción positiva en la prueba de tuberculina, los hombres presentaron 1,895 veces mayor probabilidad de dar positivo a la prueba de tuberculina que las mujeres. Conclusiones: la frecuencia de infección tuberculosa latente en estudiantes de la carrera de Medicina fue 19,3% y la variable que presentó asociación estadística a la prueba de tuberculina positiva fue el sexo masculino.

Introduction: Latent tuberculosis infection is a state of delayed cellular hypersensitivity immune response of the organism to stimulation by Mycobacterium tuberculosis antigens without clinical and radiological evidence of tuberculosis. It can be diagnosed by tuberculin test or tuberculin purified protein derivative. Objectives: To determine the frequency of latent tuberculosis infection in medical students and the variables associated with a positive reaction in the tuberculin test. Methodology: A descriptive cross-sectional study was carried out, in which the tuberculin test was made by the Mantoux method using 0.1 ml of purified protein derivative of Tubersol tuberculin in students of the medicine career of a university. Results: Two hundred ninety students participated. The frequency of latent tuberculosis infection was 19.3%. When relating the demographic variables to the positive reaction in the tuberculin test, men were 1,895 times more likely to test positive for the tuberculin test than women. Conclusions: The frequency of latent tuberculosis infection in medical students was 19.3% and the variable that presented a statistical association with the positive tuberculin test was male sex.

Tuberculin skin test versus QuantiFERON-TB gold in-tube for latent tuberculosis screening in people living with HIV in a resource-limited setting.

OBJECTIVE: To compare QuantiFERON-TB Gold-in-Tube (QFT) and tuberculin skin test (TST) in the diagnosis of latent tuberculosis infection (LTBI) among people living with HIV (PLWHIV). METHODS: A cross-sectional study was carried out between 2017-2018. Tuberculin skin test and QFT were performed and their concordance was measured. The gold standard for LTBI was defined as positivity to any of the tests. A logistic regression model was carried out to predict the QFT result in patients with a negative TST. RESULTS: A total of 510 PLWHIV were included, with 409 (80.2%) being male. The mean age of the patients was 41.3 ± 11.8 years. The median time since HIV diagnosis was 5 years (IQR 2-10), with a median CD4+ count of 541 (IQR 340-757) cells/mm3. Overall, 20 patients had an isolated TST+, 22 an isolated QFT+ and 15 had both positive. Concordance between tests showed a kappa coefficient of .37. Overcrowding was the only predictor for a positive QFT after a negative TST (p = .003). CONCLUSION: There was fair agreement between tests in PLWHIV. In conditions of limited access to QTF, a TST-based strategy could be considered, with sequential use of QTF in high-risk patients with a negative result, especially those who live in overcrowded conditions.

Multicenter Analysis of Attrition from the Pediatric Tuberculosis Infection Care Cascade in Boston.

OBJECTIVE: To characterize losses from the pediatric tuberculosis (TB) infection care cascade to identify ways to improve TB infection care delivery. STUDY DESIGN: We conducted a retrospective cohort study of children (age <18 years) screened for TB within 2 Boston-area health systems between January 2017 and May 2019. Patients who received a tuberculin skin test (TST) and/or an interferon gamma release assay (IGRA) were included. RESULTS: We included 13 353 tests among 11 622 patients; 93.9% of the tests were completed. Of 199 patients with positive tests for whom TB infection evaluation was clinically appropriate, 59.3% completed treatment or were recommended to not start treatment. Age 12-17 years (vs < 5 years; aOR 1.59; 95% CI, 1.32-1.92), non-English/non-Spanish language preference (vs English; aOR, 1.34; 95% CI, 1.02-1.76), and receipt of an IGRA (vs TST, aOR, 30.82; 95% CI, 21.92-43.34) were associated with increased odds of testing completion. Odds of testing completion decreased as census tract social vulnerability index quartile increased (ie, social vulnerability worsened; most vulnerable quartile vs least vulnerable quartile, aOR, 0.77; 95% CI, 0.60-0.99). Odds of completing treatment after starting treatment were higher in females (vs males; aOR, 2.35; 95% CI, 1.14-4.85) and were lower in patients starting treatment in a primary care clinic (vs TB/infectious diseases clinic; aOR, 0.44; 95% CI, 0.27-0.71). CONCLUSIONS: Among children with a high proportion of negative TB infection tests, completion of testing was high, but completion of evaluation and treatment was moderate. Transitions toward IGRA testing will improve testing completion; interventions addressing social determinants of health are important to improve treatment completion.

Avances en tuberculosis en el 54° Congreso Chileno de enfermedades respiratorias. 3a parte: Prevención de la tuberculosis activa mediante el tratamiento de la tuberculosis latente / Advances in tuberculosis at the 54th Chilean Congress of Respiratory Diseases. Part 3: prevention of active tuberculosis by treating latent tuberculosis

La infección tuberculosa latente (ITL) es un estado asintomático de la infección por Mycobacterium tuberculosis incapaz de transmitir la infección a otros, pero con el potencial de originar una tuberculosis (TBC) activa en el infectado, especialmente ante la presencia de factores de riesgo inmunológico. Es importante en personas de riesgo de desarrollar TBC reconocer la ITL utilizando test como la reacción a la tuberculina (PPD o TST) y los ensayos de liberación de Interferón-γ (IGRAs). Sin embargo, estos tests tienen limitaciones en su capacidad de predicción de riesgo de evolución de infección a enfermedad lo que conlleva a tener que tratar muchas personas para evitar algún caso de enfermedad. Nuevos tests se encuentran en desarrollo para mejorar la sensibilidad de reconocimiento de la ITL, distinguir infecciones recientes (que tienen el mayor riesgo de progresión a enfermedad) e incluso con la capacidad de detectar enfermedad subclínica o inicial. Para reducir la probabilidad de enfermar por TBC se utilizan tratamientos preventivos con fármacos, pero la cobertura mundial de esta terapia es reducida y la adherencia a terapias auto-administradas, como en el caso del uso de isoniazida diaria oral, es también baja. Otro problema de esta terapia son los riesgos de reacciones adversas (hepatitis, erupciones cutáneas) aunque no frecuentes. La recomendación de terapia actual de la ITL incluye el uso de rifamicinas y sus derivados. La asociación de isoniazida con rifapentina en una dosis semanal durante tres meses, administrada bajo supervisión, es la terapia de primera línea para mayores de 2 años, mostrando menos riesgo de hepatotoxicidad y mayor adherencia.

Latent Tuberculosis infection (LTBI) is the asymptomatic state of infection caused by Mycobacterium tuberculosis. Although untransmissible, LTBI can progress to active tuberculosis (TB), especially in people with immune risk factors. It is important to recognize LTBI in people at risk of developing TB; tuberculin skin test (PPD or TST) or interferon-γ release assays (IGRAs) are current diagnostic tests. However, these tests have limitations in their ability to predict subjects who will evolve from infection to disease; consequently, a large number of people with LTBI need treatment to avoid a reduced number of future TB disease cases. Newer tests are under development to improve the sensitivity in recognizing LTBI, distinguish recent infections with highest risk of progression to disease, and even be able to detect initial subclinical disease. Antimicrobial preventive treatment effectively reduces the probability of getting sick with TB, but worldwide availability of TB preventive therapy is limited, and adherence to self-administered therapies, as in the case of the use of daily oral isoniazid, is low. Adverse reactions risk (hepatitis, skin rash) although infrequent, is another problem with these therapies. Currently, LTBI management guidelines include regimens with use of rifamycins and their derivatives. The combination of isoniazid and rifapentine in a weekly dose for three months administered under supervision is the first line choice for LTBI therapy in those over 2 years of age, showing less hepatoxicity risk and greater adherence.

Incidence, Diagnosis and Treatment of Otorhinolaryngologicl, Head and Neck Tuberculosis: A Prospective Clinical Study

Abstract Introduction Tuberculosis is a disease of diversified presentation. It affects almost all organs in the body, and otorhinolaryngological, head and neck involvement is not an exception. Objective To increase awareness about the different clinical presentations of otorhinolaryngological, head and neck tuberculosis, the techniques employed to diagnose it, and to assess the response to the treatment. Methods We conducted a prospective study of 114 patients who presented primarily with otorhinolaryngological, head and neck tuberculosis. Routine blood investigations, chest radiographs, the tuberculin test, and sputum examination for the presence of acid-fast bacilli were performed in all cases. Site-specific investigations were performed in relevant cases only. The patients were treated according to the antitubercular treatment (ATT) regimen recommended by the Indian Ministry of Health and Family Welfare's National Tuberculosis Elimination Program (NTEP), and they were followed up clinically two and six months after starting the ATT. Results Tubercular cervical lymphadenopathy was the most common clinical presentation (85.96%), followed by deep neck abscess (5.27%). Fine-needle aspiration cytology proved to be a reliable tool for the diagnosis of tubercular lymphadenopathy. Improvement at the end of 2 and 6 months of the ATT was observed in 90.35% and 96.50% of the cases respectively. Conclusion The diagnosis of otorhinolaryngological, head and neck tuberculosis requires a high index of clinical suspicion, and the ATT proved to be very effective in reducing the severity of the disease.

[Modality proposal of tuberculosis infection screening in high school contacts]. / Propuesta de modalidad de catastro de infección tuberculosa en contactos escolares de colegios secundarios.

The systematic registry of contacts with the objective of identifying and treating those with tuberculosis infection is one of the pillars established by the WHO in the end Tuberculosis Strategy. The risk of tuberculosis infection in school contacts, although lower than in households, is significant. However, compliance with preventive treatment is low and several points are open to discussion, such as the cutoff of the tuberculin test to be used, the usefulness of starting a chemoprophylactic treatment in the absence of confirmed infection or carrying out studies in contacts of non-bacilliferous index cases. This paper addresses these issues and proposes, with updated evidence, a screening modality for contacts in higher education institutions. This screening proposes to identify those infected using the cut-off point of 5 mm in the tuberculin test, offering preventive treatment and active follow-up only to those with a positive test.

El catastro sistemático de contactos con el objetivo de identificar y tratar a aquellos con infección tuberculosa es uno de los pilares establecidos por la OMS en su Estrategia de Fin a la Tuberculosis. El riesgo de infección tuberculosa en contactos escolares, aunque menor que en los domiciliarios, es significativo. Sin embargo, es bajo el cumplimiento del tratamiento preventivo y varios puntos se prestan a discusión, como ser el corte de la prueba tuberculínica a utilizar, el beneficio de iniciar un tratamiento quimioprofiláctico en ausencia de infección demostrada o de realizar estudios en contactos de casos índice no bacilíferos. Este escrito aborda dichos temas y propone, con evidencia actualizada, una modalidad de estudio para contactos en instituciones de enseñanza secundaria. Dicho catastro propone identificar a los infectados utilizando el punto de corte de 5 mm en la prueba de tuberculina, ofreciendo tratamiento preventivo y seguimiento activo solamente a aquellos con una prueba positiva.

Propuesta de modalidad de catastro de infección tuberculosa en contactos escolares de colegios secundarios / Modality proposal of tuberculosis infection screening in high school contacts

Resumen El catastro sistemático de contactos con el objetivo de identificar y tratar a aquellos con infección tuberculosa es uno de los pilares establecidos por la OMS en su Estrategia de Fin a la Tuberculosis. El riesgo de infección tuberculosa en contactos escolares, aunque menor que en los domiciliarios, es significativo. Sin embargo, es bajo el cumplimiento del tratamiento preventivo y varios puntos se prestan a discusión, como ser el corte de la prueba tuberculínica a utilizar, el beneficio de iniciar un tratamiento quimioprofiláctico en ausencia de infección demostrada o de realizar estudios en contactos de casos índice no bacilíferos. Este escrito aborda dichos temas y propone, con evidencia actualizada, una modalidad de estudio para contactos en instituciones de enseñanza secundaria. Dicho catastro propone identificar a los infectados utilizando el punto de corte de 5 mm en la prueba de tuberculina, ofreciendo tratamiento preventivo y seguimiento activo solamente a aquellos con una prueba positiva.

Abstract The systematic registry of contacts with the objective of identifying and treating those with tuberculosis infection is one of the pillars established by the WHO in the end Tuberculosis Strategy. The risk of tuberculosis infection in school contacts, although lower than in households, is significant. However, compliance with preventive treatment is low and several points are open to discussion, such as the cutoff of the tuberculin test to be used, the usefulness of starting a chemoprophylactic treatment in the absence of confirmed infection or carrying out studies in contacts of non-bacilliferous index cases. This paper ad dresses these issues and proposes, with updated evidence, a screening modality for contacts in higher education institutions. This screening proposes to identify those infected using the cut-off point of 5 mm in the tuberculin test, offering preventive treatment and active follow-up only to those with a positive test.

The clinical utility of tuberculin skin tests: a single-center experience

Background: Tuberculin skin test (TST) has played an essential in the diagnosis of latent tuberculosis infection (LTBI) for nearly a century. Objective: This study aimed to investigate the general characteristics of patients tested with TST in a tertiary hospital within two years. Methods: All patients who were evaluated to screen for tuberculosis and received a TST were included. The Mantoux method was used for TST administration. Results: A total of 661 patients, 345 (52.2%) men and 316 (47.8%) women, with a mean age of 43.0 ±15.9 years, were included in the study. Accordingly, TST was performed prior to anti-TNF biological agent therapy for 50% (331) of the participants, for LTBI screening before solid organ and/or hematological stem cell transplantation for 20.4% (135), for screening following contact with tuberculosis for 25.1% (166), for screening of healthcare professionals for 1.1% (7), and medical report for 3.3% (22). 2.7% of the patients who took TST were diagnosed with active tuberculosis (14 with pulmonary tuberculosis and 4 with extrapulmonary tuberculosis). QuantiFERON-TB Gold (QFT) test was performed in 332 (50.2%) patients with anergic TST results. According to TST and QFT test results, 28.3% (187) of the patients were started on tuberculosis prophylaxis. Conclusion: While TST is most performed for LTBI screening prior to biological agent therapy, almost one-fourth of patients taking TST require tuberculosis prophylaxis. On the other hand, about half of the patients require an additional QFT test.

Antecedentes: La prueba de la tuberculina ha jugado un papel fundamental en el diagnóstico de la infección latente por tuberculosis durante casi un siglo. Objetivo: Investigar las características generales de los pacientes a los que se les realizó la prueba de tuberculina en un hospital de tercer nivel. Métodos: Se incluyeron todos los pacientes que fueron incluidos en un tamizaje de tuberculosis mediante la prueba de tuberculina. Se utilizó el método de Mantoux para la administración de esta prueba. Resultados: Se incluyeron en el estudio un total de 661 pacientes, 345 (52.2%) hombres y 316 (47.8%) mujeres, con una edad media de 43.0 ±15.9 años. La prueba de tuberculina se realizó en el 50% (331) de los participantes, antes de la terapia con agentes biológicos anti-TNF; En el 20.4% (135) se hizo la prueba antes del trasplante de órganos sólidos y/o células madre hematológicas; para el 25.1% (166) se realizó tras contacto con la tuberculosis, el 1.1% (7) para tamizaje de los profesionales sanitarios y con informe médico para el 3.3% (22). El 2.7% de los pacientes que se realizaron la prueba de tuberculina fueron diagnosticados con tuberculosis activa (14 pulmonar y 4 extrapulmonar). La prueba QuantiFERON-TB Gold (QFT) se realizó en 332 (50.2 %) pacientes con resultados anérgicos para tuberculina. Según los resultados de las pruebas de tuberculina y QFT, el 28.3% (187) de los pacientes iniciaron profilaxis antituberculosa. Conclusión: Si bien la prueba de tuberculina se realiza comúnmente para la detección de tuberculosis latente antes de la terapia con agentes biológicos, casi una cuarta parte de los pacientes que se les hizo la prueba de tuberculina requieren profilaxis para tuberculosis. Por otro lado, aproximadamente la mitad de los pacientes requieren una prueba QFT adicional.

US Postarrival Evaluation of Immigrant and Refugee Children with Latent Tuberculosis Infection Diagnosed Overseas, 2007-2019.

OBJECTIVE: To assess outcomes from the US postarrival evaluation of newly arrived immigrant and refugee children aged 2-14 years who were diagnosed with latent tuberculosis infection (LTBI) during a required overseas medical examination. STUDY DESIGN: We compared overseas and US interferon-γ release assay (IGRA)/tuberculin skin test (TST) results and LTBI diagnosis; assessed postarrival LTBI treatment initiation and completion; and evaluated the impact of switching from TST to IGRA to detect Mycobacterium tuberculosis infection overseas. RESULTS: In total, 73 014 children were diagnosed with LTBI overseas and arrived in the US during 2007-2019. In the US, 45 939 (62.9%) completed, and 1985 (2.7%) initiated but did not complete a postarrival evaluation. Among these 47 924 children, 30 360 (63.4%) were retested for M tuberculosis infection. For 17 996 children with a positive overseas TST, 73.8% were negative when retested by IGRA. For 1051 children with a positive overseas IGRA, 58.0% were negative when retested by IGRA. Overall, among children who completed a postarrival evaluation, 18 544 (40.4%) were evaluated as having no evidence of TB infection, and 25 919 (56.4%) had their overseas LTBI diagnosis confirmed. Among the latter, 17 229 (66.5%) initiated and 9185 (35.4%) completed LTBI treatment. CONCLUSIONS: Requiring IGRA testing overseas could more effectively identify children who will benefit from LTBI treatment. However, IGRA reversions may occur, highlighting the need for individualized assessment for risk of infection, progression, and poor outcome when making diagnostic and treatment decisions. Strategies are needed to increase the proportions receiving a postarrival evaluation and completing LTBI treatment.

The clinical utility of tuberculin skin tests: a single-center experience.

Background: Tuberculin skin test (TST) has played an essential in the diagnosis of latent tuberculosis infection (LTBI) for nearly a century. Objective: This study aimed to investigate the general characteristics of patients tested with TST in a tertiary hospital within two years. Methods: All patients who were evaluated to screen for tuberculosis and received a TST were included. The Mantoux method was used for TST administration. Results: A total of 661 patients, 345 (52.2%) men and 316 (47.8%) women, with a mean age of 43.0 ±15.9 years, were included in the study. Accordingly, TST was performed prior to anti-TNF biological agent therapy for 50% (331) of the participants, for LTBI screening before solid organ and/or hematological stem cell transplantation for 20.4% (135), for screening following contact with tuberculosis for 25.1% (166), for screening of healthcare professionals for 1.1% (7), and medical report for 3.3% (22). 2.7% of the patients who took TST were diagnosed with active tuberculosis (14 with pulmonary tuberculosis and 4 with extrapulmonary tuberculosis). QuantiFERON-TB Gold (QFT) test was performed in 332 (50.2%) patients with anergic TST results. According to TST and QFT test results, 28.3% (187) of the patients were started on tuberculosis prophylaxis. Conclusion: While TST is most performed for LTBI screening prior to biological agent therapy, almost one-fourth of patients taking TST require tuberculosis prophylaxis. On the other hand, about half of the patients require an additional QFT test.

Antecedentes: La prueba de la tuberculina ha jugado un papel fundamental en el diagnóstico de la infección latente por tuberculosis durante casi un siglo. Objetivo: Investigar las características generales de los pacientes a los que se les realizó la prueba de tuberculina en un hospital de tercer nivel. Métodos: Se incluyeron todos los pacientes que fueron incluidos en un tamizaje de tuberculosis mediante la prueba de tuberculina. Se utilizó el método de Mantoux para la administración de esta prueba. Resultados: Se incluyeron en el estudio un total de 661 pacientes, 345 (52.2%) hombres y 316 (47.8%) mujeres, con una edad media de 43.0 ±15.9 años. La prueba de tuberculina se realizó en el 50% (331) de los participantes, antes de la terapia con agentes biológicos anti-TNF; En el 20.4% (135) se hizo la prueba antes del trasplante de órganos sólidos y/o células madre hematológicas; para el 25.1% (166) se realizó tras contacto con la tuberculosis, el 1.1% (7) para tamizaje de los profesionales sanitarios y con informe médico para el 3.3% (22). El 2.7% de los pacientes que se realizaron la prueba de tuberculina fueron diagnosticados con tuberculosis activa (14 pulmonar y 4 extrapulmonar). La prueba QuantiFERON-TB Gold (QFT) se realizó en 332 (50.2 %) pacientes con resultados anérgicos para tuberculina. Según los resultados de las pruebas de tuberculina y QFT, el 28.3% (187) de los pacientes iniciaron profilaxis antituberculosa. Conclusión: Si bien la prueba de tuberculina se realiza comúnmente para la detección de tuberculosis latente antes de la terapia con agentes biológicos, casi una cuarta parte de los pacientes que se les hizo la prueba de tuberculina requieren profilaxis para tuberculosis. Por otro lado, aproximadamente la mitad de los pacientes requieren una prueba QFT adicional.

Scaling up investigation and treatment of household contacts of tuberculosis patients in Brazil: a cost-effectiveness and budget impact analysis.

Background: In Brazil, investigation and treatment of tuberculosis infection (TBI) in households contacts (HHC) of TB patients is not a priority. We estimated the cost-effectiveness and budget-impact of scaling-up an enhanced HHC management in Brazil. Methods: We conceptualized a cascade-of-care that captures how HHC of tuberculosis patients are investigated in Brazil (status quo) and two enhanced strategies for management of HHC focusing on: (1) only tuberculosis disease (TBD) detection and, (2) TBD and TBI detection and treatment. Effectiveness was the number of HHC diagnosed with TBD and completing TBI treatment. Proportions in the cascades-of-care were derived from a meta-analysis. Health-system costs (2019 US$) were based on literature and official data from Brazil. The impact of enhanced strategies was extrapolated using reported data from 2019. Findings: With the status quo, 0 (95% uncertainty interval: 0-1) HHC are diagnosed with TBD and 2 (0-16) complete TBI treatment. With strategy(1), an additional 15 (3-45) HHC would be diagnosed with TBD at a cost of US$346 each. With strategy(2), 81 (19-226) additional HHC would complete TBI treatment at a cost of US$84 each. A combined strategy, implemented nationally to enhance TBD detection and TBI treatment would result in an additional 9,711 (845-28,693) TBD being detected, and 51,277 (12,028-143,495) more HHC completing TBI treatment each year, utilizing 10.9% and 11.6% of the annual national tuberculosis program budget, respectively. Interpretation: Enhanced detection and treatment of TBD and TBI among HHC in Brazil can be achieved at a national level using current tools at reasonable cost. Funding: None.

Intradermal comparative cervical tuberculin test in the diagnosis of caprine tuberculosis.

Tuberculosis remains one of the most important infectious diseases with well-known zoonotic nature that affect humans, wildlife, and domestic animals, including goats. Nonetheless, no intradermal tuberculin test has been standardized for caprine diagnosis of tuberculosis. The present study investigated the intradermal comparative cervical tuberculin test (ICCTT) in the diagnosis of tuberculosis among 60 goats from farms with history of tuberculosis. The cutoff applied to goats was based on a study where goats had been experimentally infected with Mycobacterium bovis and Mycobacterium avium. Clinical examination, bacteriological culture, and histopathological staining were assessed to the diagnosis. Isolates compatible with mycobacteria were subjected for molecular diagnosis based on gyrB-restriction fragment length polymorphism (RFLP) analysis and PCR restriction-enzyme analysis (PRA) of hsp65 gene by BstEII and HaeIII, namely PRA-hsp65 assay. From all goats, 60% (n = 36/60), 3.3% (n = 2/60), and 36.7% (n = 22/60) showed positive, inconclusive, and negative reactions, respectively. Out of 36 goats with ICCTT positive, 75% (n = 27/36) had isolation of mycobacteria and were detected M. bovis by gyrB-RFLP. Molecular diagnosis and histopathological findings compatible with tuberculosis showed 86.1% (n = 31/36) concordance with the ICCTT. When compared ICCTT with M. bovis isolation, gyrB-RFLP, and histopathology, the better arithmetic means of sensitivity and specificity were 2.5 mm for ICCTT compared with M. bovis isolation and gyrB-RFLP, and 4.55 mm when compared with histopathology. Both receiver operating characteristic (ROC) curves presented statistical significance (P < 0.001). The identification of other mycobacteria, e.g., M. kansasii, M. flavescens, M. avium, M. florentinum, M. lentiflavum, M. simiae, and Corynebacterium pseudotuberculosis, not influenced positive results in ICCTT. The concordance between bacteriological, histopathological, and molecular identification with ICCTT findings indicate that the tuberculin test may be used as a valuable tool for diagnosis of caprine tuberculosis and reinforce the importance of association of methods to diagnostic of the disease from animal origin.

Indirect ELISA as a complementary diagnostic method of bovine tuberculosis / ELISA indreto como método complementar de diagnóstico da tuberculose bovina

Bovine tuberculosis is an economic and health problem, requiring precise diagnostic methods for its control and eradication. The aim of this study was to evaluate the performance of a commercial enzyme-linked immunosorbent assay (ELISA) test for the diagnosis of bovine tuberculosis. A total of 1,644 cattle from eight dairy herds were evaluated using the comparative cervical tuberculin test (CCTT). Three of the herds had no recent tuberculosis infection, and the other five had shown positive results in a previous tuberculin test. For the serological diagnosis of tuberculosis, a commercial ELISA antibody test kit for Mycobacterium bovis was used. Serum samples from 846 cattle from the eight herds were evaluated using ELISA for M. bovis. Animals that were positive based on either CCTT or ELISA for M. bovis or both were sent to slaughter. Samples of their lungs, livers, and lymph nodes were collected and stored under refrigeration for microbiological culture and subsequent confirmation by polymerase chain reaction. Samples from the same tissues were also fixed with 10% formaldehyde in bottles for histopathological examination and stained with hematoxylin and eosin (HE). Of the 1,644 cattle, 61 were considered positive and 65 inconclusive based on CCTT. Retesting of the inconclusive samples identified an additional 19 positive cases, totaling 80 (4.8%) CCTT-positive animals from five herds. ELISA for M. bovis identified 4.2% (36/846) positive cattle, of which 35 were considered negative and one inconclusive based on CCTT. Of the 36 positive cases identified by ELISA for M. bovis, 27 were euthanized, 11% (3/27) showed suggestive lesions of tuberculosis on macroscopic examination, and two were confirmed by histological, microbiological, and PCR methods. The weak association of ELISA for M. bovis with the results obtained by macroscopic, histological, and microbiological isolation indicates the fragility of ELISA performance in field conditions. Therefore, it is suggested that its use as a complementary method for herd sanitation be based on the local epidemiological situation.

A tuberculose bovina é um problema econômico mundial e de saúde, que requer métodos de diagnóstico precisos para controle e erradicação. Objetivou-se com este estudo avaliar o desempenho de um teste comercial de ELISA no diagnóstico da tuberculose bovina. Foram avaliados pelo teste cervical comparativo (TCC) 1644 bovinos, provenientes de oito rebanhos de exploração leiteira, sendo três deles sem histórico recente da doença, e outros cinco com resultados positivos no último exame de tuberculinização. Para o diagnóstico sorológico da tuberculose utilizou-se um kit comercial de ELISA Mycobacterium bovis antibody test (ELISA M. bovis). Amostras de soro sanguíneo de 846 bovinos provenientes dos mesmos rebanhos foram também avaliadas no ELISA M. bovis. Os bovinos positivos no TCC e/ou ELISA M. bovis foram encaminhados para o abate sanitário. Dos positivos no ELISA para M. bovis foi realizado o exame macroscópico das carcaças e classificação das mesmas em: com presença ou ausência de lesões. Amostras de pulmão, fígado, e linfonodos, foram colhidas em duplicata para realização dos exames de cultivo microbiológico com posterior confirmação por PCR, e exame histopatológico com coloração de hematoxilina e eosina (HE). Dos 1,644 bovinos, 61 foram considerados positivos e 65 inconclusivos no TCC. O reteste dos inconclusivos identificou mais 19 positivos. No total, 80 (4,8%) bovinos positivos no TCC, provenientes de 5 rebanhos foram encaminhados para abate. O ELISA para M. bovis identificou 4,2% (36/846) de bovinos positivos, sendo 36 considerados negativos e um inconclusivo no exame de tuberculinização. Dos positivos no ELISA para M. bovis, 27 foram eutanasiados, e no exame macroscópico das carcaças 11% (3/27) dos animais apresentaram lesões sugestivas de tuberculose, e em apenas dois houve confirmação da doença pelos métodos histológico, microbiológico e PCR. A baixa associação dos resultados obtidos no ELISA para M. bovis com os exames macroscópico, histológico e isolamento microbiológico apontam para a fragilidade do desempenho do ELISA para o diagnóstico de tuberculose. Sugere-se assim que seu uso como método complementar para saneamento de rebanhos, seja adotado com cautela e considere a situação epidemiológica local.