Prevalencia de infección tuberculosa latente e incidencia de viraje tuberculínico en contactos escolares mayores de 5 años en la Ciudad Autónoma de Buenos Aires / Prevalence of latent tuberculosis infection and incidence of tuberculin conversion among school contacts older than 5 years in the City of Buenos Aires

Introducción. La tuberculosis continúa siendo un problema frecuente en contextos de vulnerabilidad socioeconómica. El objetivo principal fue establecer la prevalencia de infección latente y viraje tuberculínico en contactos escolares de casos de tuberculosis. Población y métodos. En un área programática del sur de la ciudad, se evaluó la prevalencia de infección y viraje tuberculínico de 691 niñas, niños y adolescentes utilizando la prueba cutánea de tuberculina. Se investigó la asociación entre pérdida de seguimiento por parte del equipo de salud y características demográficas, escolares y asistencia inicial, y se describió el grado de adherencia cuando la quimioprofilaxis con isoniacida fue indicada. Resultados. Según las definiciones consideradas, la prevalencia de infección latente fue entre el 3,4 % (IC95 %: 2,3-5,2) y el 11,6 % (IC95 %: 9,3-14,4) de los 610 contactos con al menos una prueba cutánea aplicada. La incidencia de viraje tuberculínico se encontró entre el 0,3 % y el 6,8 % de los 294 evaluados. La edad mayor de 18 años, la mayor prevalencia de necesidades básicas insatisfechas en la comuna escolar, la pertenencia al turno escolar vespertino, la negatividad en la baciloscopia del caso índice y la ausencia de aplicación de la prueba cutánea inicial se asociaron con pérdida de seguimiento del contacto. Conclusiones. La incidencia de viraje tuberculínico en contactos escolares fue baja. La adherencia a isoniacida continúa siendo limitada. Se identificaron factores asociados con la pérdida de seguimiento de contactos que podrían orientar estrategias necesarias para mejorar este proceso.

Introduction. Tuberculosis continues to be a common problem in settings of socioeconomic vulnerability. Our primary objective was to establish the prevalence of latent infection and tuberculin conversion among school contacts of tuberculosis cases. Population and methods. In a programmatic area in the south of the City of Buenos Aires, the prevalence of latent infection and tuberculin conversion was assessed in 691 children and adolescents using the tuberculin skin test. The association between loss to follow-up by the health care team and the demographic, school, and baseline care characteristics was studied, and the level of adherence when isoniazid chemoprophylaxis was indicated was described. Results. According to established definitions, the prevalence of latent infection was between 3.4% (95% confidence interval [CI]: 2.3­5.2) and 11.6% (95% CI: 9.3­14.4) in the 610 contacts with at least one skin test. The incidence of tuberculin conversion was between 0.3% and 6.8% in the 294 assessed participants. Age older than 18 years, a higher prevalence of unmet basic needs in the school district, attending the afternoon school shift, negative sputum smear results in the index case, and absence of baseline skin test were associated with contact lost to follow-up. Conclusions. The incidence of tuberculin conversion among school contacts was low. Adherence to isoniazid treatment remains limited. Factors associated with loss of contact tracing were identified, which may guide strategies necessary to improve this process.

Research progress in transcriptional and immunological biomarkers associated with tuberculosis infection / 中华预防医学杂志

Tuberculosis (TB) is an infectious disease that poses a serious threat to human health. About a quarter of the world's population were infected with Mycobacterium tuberculosis in 2020, and the majority of them were latently infected. Approximately 5%-10% of the population with latent tuberculosis infection may progress to active TB disease. Identifying latent TB infection from active TB by biomarkers and screening people with latent TB infection at high risk of progression for preventive treatment by biomarkers that can reliably predict the progression is one of the most effective strategies to control TB. This article reviews the progress of research on transcriptional and immunological biomarkers for identifying TB infection and predicting the progression from latent infection to active TB, with the aim of providing new ideas for tuberculosis control.

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.

Tuberculosis latente: diagnóstico y tratamiento actual / Latent tuberculosis: current diagnosis and treatment

Resumen La infección tuberculosa latente (TL) afecta al 23% de la población y constituye un reservorio de tuberculosis (TBC) ya que 10% progresa hacia una TBC. La TL se reconoce por pruebas como la tuberculina (PPD o TST) y los ensayos de liberación de Interferón gama (IGRAs). La sensibilidad de IGRAs (versión Quantiferon TB Gold plus) es 94% y del PPD 77%. La especificidad del Quantiferon TB Gold Plus es 97% y del PPD 68%. El valor predictivo de progresión a TBC activa de estas pruebas es bajo (PPD: 1,5%, IGRAs: 2,7%) pero mejora en personas de alto riesgo de contraer TBC (PPD: 2,4%, IGRAs: 6,8%). Las personas con pruebas negativas que posteriormente presentan viraje (prueba positiva) tienen mayor riesgo de progresión a TBC activa. Estas pruebas son útiles en el seguimiento de contactos intradomiciliarios, extranjeros de países con altas tasas de TBC, inmunosuprimidos, enfermedad renal crónica, diabetes, silicosis y secuelas pulmonares de TBC no tratada. En la terapia de TL se utiliza isoniazida (H) auto-administrada por plazos de 6 a 12 meses con eficacia protectora de 60% y riesgo de toxicidad hepática de 2% pero con baja adherencia (50-70%). La asociación de H con rifapentina en dosis única semanal durante 12 semanas tiene eficacia de 81%, adherencia de 82% y baja toxicidad hepática (0,4%). Nuevos biomarcadores de TL y vacunas que mejoren la inmunidad en TL se encuentran en estudio. El tratamiento de la TL puede reducir la incidencia de TBC a largo plazo.

Latent tuberculosis infection (LT) affects 23% of the population and constitutes a reservoir of tuberculosis (TB) as 10% progresses to TB. LT is recognized by tests such as tuberculin (PPD or TST) and Interferon gamma release assays (IGRAs). The sensitivity of IGRAs (Quantiferon TB Gold plus version) is 94% and PPD 77%. The specificity of Quantiferon TB Gold Plus is 97% and PPD 68%. The predictive value of progression to active TB of these tests is low (PPD: 1.5%, IGRAs: 2.7%) but improves in people at high risk of contracting TB (PPD: 2.4%, IGRAs: 6.8%). People with negative tests who subsequently turn around (positive) have a higher risk of progression to active TB. These tests are useful in the follow-up of intra-household contacts, foreigners from countries with high rates of TB, immunosuppressed, chronic kidney disease, diabetes, silicosis and pulmonary sequelae of untreated TB. In LT therapy, self-administered isoniazid (H) is used for periods from 6 to 12 months with protective efficacy of 60% and risk of liver toxicity of 2%, but with low adherence (50-70%). The association of H with rifapentine in a single weekly dose for 12 weeks has efficacy of 81%, adherence of 82% and low liver toxicity (0.4%). New LT biomarkers and vaccines that improve immunity in LT are under study. Treatment of LT may reduce the incidence of TB in the long term.

Prevalence of latent tuberculosis infection among patients with interstitial lung disease requiring immunosuppression / Prevalência de infecção latente por tuberculose em pacientes com doença pulmonar intersticial com necessidade de imunossupressão

ABSTRACT Objective To characterize the prevalence of latent tuberculosis infection (LTBI) in patients with interstitial lung diseases (ILDs) requiring immunosuppression. Only 5 to 10% of individuals infected with Mycobacterium tuberculosis develop tuberculosis, and certain groups of patients have an increased risk of illness, such as the immunocompromised. Patients with ILDs are frequently treated with immunosuppressants and, therefore, might have a higher risk of developing the disease. Methods Prospective study conducted at the ILD reference center of the Federal University of Paraná from January 2019 to December 2020. The screening of LTBI was performed with the use of the tuberculin skin test (TST). Results The sample consisted of 88 patients, of whom 64.8% were women, with a mean age of 61.4 years. The most frequent diagnoses were autoimmune rheumatic disease ILD (38.6%) and hypersensitivity pneumonitis (35.2%). The most common immunosuppressant in use at the time of the TST was prednisone, either in combination with mycophenolate (19.3%) or alone (17.1%). The majority of participants had fibrotic lung disease, characterized by a reticular interstitial pattern on chest computed tomography (79.5%) and moderate to severe functional impairment (mean FVC 69.2%). A prevalence of LTBI of 9.1% (CI 95%, 2.1%-15.1%) was found, with a TST median of 13. Conclusion Patients with ILD who are treated with immunosuppressants are not commonly screened for LTBI, despite being under a greater risk of progression to active disease. This study suggests the need for a more cautious approach to these patients.

RESUMO Objetivo Caracterizar a prevalência de Infecção Latente por Tuberculose (ILTB) em pacientes com Doenças Pulmonares Intersticiais (DPIs) que necessitam de imunossupressão. Apenas 5 a 10% dos indivíduos infectados pelo Mycobacterium tuberculosis desenvolvem tuberculose, sendo que certos grupos de pacientes apresentam maior risco de doença, tais como os imunocomprometidos. Pacientes com DPIs são frequentemente tratados com imunossupressores, portanto, podem apresentar maior risco de desenvolver a doença. Métodos Estudo prospectivo conduzido no Centro de Referência para DPI da Universidade Federal do Paraná (UFPR), entre Janeiro de 2019 e Dezembro de 2020. O rastreio de ILTB foi realizado por meio da Prova Tuberculínica (PT). Resultados A amostra foi composta por 88 pacientes, dos quais 64,8% eram mulheres, com, em média, 61,4 anos de idade. Os diagnósticos mais frequentes foram DPI associada a doença reumática autoimune (DRAI) (38,6%) e pneumonite de hipersensibilidade (35,2%). Prednisona foi o imunossupressor mais comumente utilizado à época da PT, em combinação com micofenolato (19,3%) ou isoladamente (17,1%). A maioria dos participantes tinha doença pulmonar fibrótica, caracterizada por infiltrado reticular em tomografia computadorizada de tórax (79,5%), bem como comprometimento funcional moderado a grave (Capacidade Vital Forçada (CVF) média de 69,2%). Observou-se uma prevalência de ILTB de 9,1% (Intervalo de Confiança (IC) 95%, 2,1%-15,1%), com mediana da PT de 13. Conclusão Não é comum que pacientes com DPI tratados com imunossupressores sejam avaliados quanto à presença de ILTB, apesar de estarem sob um maior risco de progressão para doença ativa. Este estudo sugeriu a necessidade de uma abordagem mais cuidadosa em relação a esses pacientes.

Novas ferramentas para o diagnóstico de infecção latente por Mycobacterium tuberculosis / New tools for the diagnostics of latent Mycobacterium tuberculosis infection

Esta tese objetivou identificar estratégias de triagem para infecção latente por Mycobacterium tuberculosis (Mtb) ­ ILTB em profissionais de saúde que viabilizem o uso mais eficiente dos recursos disponíveis. No Brasil, recomenda-se que os profissionais de saúde, um dos grupos de risco para a ILTB, realizem triagem periódica para detecção da infecção e aqueles que apresentarem conversão aos testes de diagnóstico, indica-se o tratamento preventivo da tuberculose (TB) ­ TPT uma vez que pessoas com conversão recente apresentam elevada chance de progressão para a doença. Desenvolvemos, no primeiro artigo, um modelo preditivo para identificar profissionais de saúde com maior probabilidade de resultado negativo para dois testes de diagnóstico da ILTB a partir de uma análise secundária de dados publicados anteriormente de 708 profissionais de saúde da atenção primária, de cinco capitais brasileiras, submetidos à prova tuberculínica (PT) e ao Quantiferon®-TB Gold in-tube (QFT-IT®). Construímos um modelo preditivo utilizando árvore de classificação e regressão (CART, classification and regression tree). A avaliação do desempenho foi realizada por meio da análise receiver operating characteristics (ROC) e area under the curve (AUC). Utilizou-se o mesmo banco de dados para validação cruzada do modelo. Entre os 708 profissionais de saúde, 247 (34,9%) apresentaram resultado negativo para os testes. A CART identificou que os médicos e agentes comunitários de saúde apresentaram chances duas vezes maior de testes negativos (probabilidade = 0,60) do que os enfermeiros e técnicos/auxiliares de enfermagem (probabilidade = 0,28) naqueles com menos de 5,5 anos de atuação na atenção primária. Na validação cruzada, a acurácia do modelo preditivo foi de 68% [intervalo de confiança de 95% (IC95%) 65 ­ 71) ], AUC de 62% (IC95% 58 ­ 66), especificidade de 78% (IC95% 74 ­ 81) e sensibilidade de 44% (IC95% 38 ­ 50). Apesar do baixo poder preditivo do modelo, a CART permitiu identificar subgrupos com maior probabilidade de terem ambos os testes negativos. No segundo artigo, analisou-se a razão de custo-efetividade de dois testes de sensibilidade cutânea baseados em antígenos específicos do Mtb -Diaskintest® e C-TST® - e a do QFT-Plus® para o diagnóstico da ILTB comparadas com a estratégia diagnóstica atual (PT) entre profissionais de saúde. Desenvolveu-se um modelo analítico de decisão, representado por coorte hipotética de 100.000 profissionais de saúde, de ambos os sexos, com resultado negativo para a PT no ano anterior, horizonte temporal de cinco anos, na perspectiva do Sistema Único de Saúde. Avaliaram-se três regimes de tratamento para a ILTB: três meses de doses semanais de rifapentina (900 mg) e isoniazida (900 mg) (3HP), seis e nove meses de doses diárias de isoniazida (300 mg) (6H e 9H, respectivamente). Aplicou-se taxa de desconto de 5% na efetividade, medida em casos de TB ativa evitados, e nos custos das estratégias de triagem e de tratamento avaliados, estimados em dólares americanos (US$) com taxa média anual de 2021 de acordo com o Banco Central (US$ 1 = 5,39 reais). Foram realizadas análises de sensibilidade determinística univariada e probabilística. Os testes Diaskintest®, C-TST® e QFT-Plus® apresentam maior especificidade (0,98, 0,98 e 0,97, respectivamente). Os custos com QFT-Plus® foram maiores devido aos equipamentos, mão de obra e ao custo do kit. O Diaskintest® foi o teste mais econômico (US$ 7.042, US$ 5.781 e US$ 18.892 por caso de TB ativa evitado para os regimes de tratamento com 3HP, 6H e 9H, respectivamente), inclusive nas análises de sensibilidade. No cenário nacional, o Diaskintest® foi o teste de melhor custo-efetividade para avaliação anual dos profissionais de saúde.

This thesis aimed to identify screening strategies for tuberculosis infection (TBI) in healthcare workers (HCW) that enable the most efficient use of available resources. Investigation of TBI in HCWs is recommended in Brazil as part of the worker's pre-employment and periodic (annual) health visits. HCWs with a first tuberculin skin test (TST) induration < 10 mm are invited to repeat the test in one to three weeks to assess the booster effect (induration size increment of 10 mm). Those with a persistent TST < 10 mm will undergo a one-step TST every 12 months. TPT is recommended when conversion (10 mm increment over latest induration size) occurs. We developed, in the first manuscript, a predictive model to identify HCWs best targeted for TBI screening. We carried out a secondary analysis of previously published results of 708 HCWs working in primary care services in five Brazilian State capitals who underwent two TBI tests: tuberculin skin test and Quantiferon®-TB Gold in-tube. We used a classification and regression tree (CART) model to predict HCWs with negative results for both tests. The performance of the model was evaluated using the receiver operating characteristics (ROC) curve and the area under the curve (AUC), cross-validated using the same dataset. Among the 708 HCWs, 247 (34.9%) had negative results for both tests. CART allowed us to identify that physicians or a community health agents were twice more likely to be uninfected (probability = 0.60) than registered or aid nurse (probability = 0.28) when working less than 5.5 years in the primary care setting. In cross validation, the predictive accuracy was 68% [95% confidence interval (95%CI): 65 ­ 71], AUC was 62% (95%CI 58 ­ 66), specificity was 78% (95%CI 74 ­ 81), and sensitivity was 44% (95%CI 38 ­ 50). Despite the low predictive power of this model, CART allowed to identify subgroups with higher probability of having both tests negative. In the second manuscript, we analyzed the cost-effectiveness of two TB antigen-based skin tests (TBST) using the recombinant ESAT-6 and CFP-10 immunogens (Diaskintest® and C-TST®) and of QFT-Plus® for TBI diagnosis compared with the current standard of care, TST, among HCWs in Brazil. A state-transition Markov model was created, simulating a cohort of 100,000 HCWs (five annual cycles) for TBI treatment scenarios with 3 months of weekly doses of rifapentine (900 mg) and isoniazid (900 mg) (3HP). We adopted the Brazilian public health system perspective. Effects [tuberculosis disease (TBD) averted) and costs for screening and treating TBI were discounted at 5%. Incremental cost-effectiveness per TBD averted was calculated. Hypothetical cohort of 100,000 HCWs of both sexes with a negative result of TST in the previous year. Diaskintest®, C-TST® and QFT-Plus® tests have higher specificity (0.98, 0.98 and 0.97, respectively). Costs with QFT-Plus® were higher due to equipment, human labor and cost of the kit by test. Diaskintest® was the most cost-effective test (US$ 7,042, US$ 5,781, and US$18,892 per case of TBD averted for the 3HP, 6H, and 9H treatment regimens, respectively), including sensitivity analyses. In the Brazilian scenario, Diaskintest® is the most cost-effective test for sequential testing of HCWs.

Terapias biológicas y tuberculosis en pediatría / Biological therapies and tuberculosis in pediatrics

En los últimos años, ha habido un aumento sostenido del uso de terapias inmunomoduladoras como las terapias biológicas y en un período más reciente, de las terapias con moléculas pequeñas. Estos tratamientos constituyen un factor de riesgo más para enfermar de tuberculosis en adultos y aunque en menor grado, también en niños, especialmente con el uso de anti TNF-α, por lo que antes de iniciar una terapia biológica, hay que descartar la tuberculosis activa y la latente. En el tratamiento de una tuberculosis activa producida por un biológico se debe prolongar la etapa de continuación a 9 meses. Es importante el seguimiento clínico prolongado en años de quienes usan o han completado el uso de estas terapias. Hay que posponer la vacunación BCG en los hijos de madres que usaron terapias biológicas durante la gestación hasta la edad 6 a 12 meses de los niños. El foco de esta revisión está centrado en la tuberculosis por progresión de una forma latente a una activa o por un contacto estrecho con una persona con tuberculosis pulmonar en pacientes que reciben terapias biológicas anti TNF alfa de uso inmunoreumatológico.

In recent years, there has been a sustained increase in the use of immunomodulatory therapies such as biologic therapies and, more recently, small molecule therapies. Those therapies have become another risk factor for tuberculosis in adults and, although to lesser degree, also in children, especially some of them, such as anti-TNF α. Before starting biological therapy, active tuberculosis and latent tuberculosis must be ruled out. In the treatment of active tuberculosis caused by a biologic, the continuation stage should be extended to 9 months. Long-term clinical follow-up in years of those who use them or have completed their use, is important. BCG vaccine should be postponed in children of mother who used biologic therapies during pregnancy until the children ́s age 6 to 12 months. The focus of this review is centered on tuberculosis due to progression from a latent to an active form or due to close contact with a person with pulmonary tuberculosis in patients receiving anti-TNF alpha biological therapies for immunorheumatology use.

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.

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.

Incrementando o impacto do diagnóstico e do tratamento da infecção latente tuberculosa na saúde pública: um estudo de efetividade, sustentabilidade, viabilidade e custo-efetividade / A public health approach to increase treatment of latent tuberculosis infection: a study of effectiveness, sustainability, feasibility and cost-effectiveness

O tratamento da infecção latente da tuberculose (ILTB) é crucial para eliminar a doença. Esta tese, apresentada em dois artigos, avalia a efetividade, a sustentabilidade, a viabilidade, a razão de custo-efetividade e o impacto orçamentário de um programa de investigação para detecção e tratamento da ILTB em contatos intradomiciliares de pacientes com tuberculose no Brasil. No primeiro artigo, dois ensaios controlados consecutivos foram conduzidos. Avaliamos a efetividade, a sustentabilidade, e a viabilidade de uma intervenção em saúde pública que teve o objetivo de aumentar a proporção de início do tratamento para ILTB entre os contatos intradomiciliares de pacientes com tuberculose pulmonar ativa. No primeiro ensaio clínico controlado, 12 clínicas foram submetidas a uma avaliação padronizada, incluindo questionários administrados a pacientes com tuberculose, seus contatos intradomiciliares e profissionais de saúde, e uma análise da cascata do cuidado da ILTB. Seis clínicas foram então randomizadas para receber atividades para fortalecer o manejo da ILTB, incluindo treinamento em serviço, organização do processo de trabalho e soluções adicionais específicas de cada clínica de acordo com resultados da avaliação padronizada. No segundo ensaio, uma avaliação semelhante, mas simplificada, foi realizada em duas clínicas, que então receberam treinamento intensivo inicial e treinamento em serviço fornecido por um médico. No segundo artigo, avaliamos a razão de custo-efetividade e o impacto orçamentário ao expandir um programa fortalecido de investigação e tratamento da ILTB entre contatos intradomiciliares no Brasil. Duas estratégias otimizadas sobre o manejo dos contatos intradomiciliares foram comparadas com a situação atual (status quo) no Brasil: 1) detecção de tuberculose ativa apenas e 2) detecção de tuberculose ativa e investigação e tratamento de ILTB. Nos dois ensaios controlados, na fase de avaliação, foram observadas lacunas de conhecimento entre todos os grupos de entrevistados e, embora muitos contatos tenham sido identificados, poucos iniciaram o tratamento de ILTB. Após a implementação das soluções, o número de contatos que iniciaram o tratamento da ILTB por 100 pacientes com tuberculose aumentou em 10 [intervalo de 95% de confiança (IC): -11, 30] no primeiro estudo, em comparação com 44 (IC 95%: 26, 61), no segundo ensaio controlado. Em nossas avaliações econômicas, na estratégia otimizada de investigação e tratamento da ILTB os custos para ter um contato intradomiciliar completando o tratamento da ILTB seriam a metade daqueles para encontrar um paciente com TB ativa (158,6 vs. 299,7 dólares norte-americanos). Resultariam ainda em um importante impacto na endemia, 4.001 casos de TB seriam evitados e custariam 12% do orçamento nacional para TB. Uma abordagem de saúde pública com avaliação padronizada, seguida por treinamento inicial e treinamento em serviço intensivo mostrou-se promissora para expandir o tratamento da ILTB no Brasil.

This thesis, presented in two articles, evaluates the effectiveness, sustainability, feasibility, cost-effectiveness and budgetary impact of a program that investigates and treats latent tuberculosis infection (LTBI) among household contacts (HHC) of patients with active tuberculosis in Brazil. In the first article, we presented the results of two consecutive control trials, where we evaluated the effectiveness, sustainability and feasibility a public health intervention that aimed to increase the proportion of initiation of treatment for ILTB among HHC of patients with active tuberculosis. In the first trial, twelve clinics underwent a standardized evaluation, including questionnaires administered to tuberculosis-patients, contacts and healthcare workers and clinical data on the cascade-of-care for contacts. Six clinics were then randomized to receive LTBI strengthening activities, including monthly in-service training work process organization, and implementation of specific local solutions. In the second trial, a similar but streamlined evaluation was conducted in two clinics, who then received initial and subsequent intensive in-service training provided by a physician. In the second article, we evaluated the cost-effectiveness and budget impact of scaling-up an enhanced tuberculosis HHC program in Brazil. Two enhanced HHC management strategies were compared to the current HHC management situation in Brazil (status quo). HHC cascades-of-care were conceptualized for the status quo and for two enhanced HHC strategies: 1) active tuberculosis detection only and 2) active tuberculosis detection and LTBI investigation and treatment. In both studies, at the evaluation phase, knowledge gaps among all interviewee groups were observed, and although many contacts were identified, few started LTBI treatment. Following the implementation of solutions, the number of contacts initiating treatment per 100 TB patients increased by 10 [95% confidence interval (CI): -11, 30] in the first study, compared to 44 (95%CI: 26, 61), in the second study. In our economic evaluation, we found that for an enhanced HHC management cascade-of-care, the costs to have one additional HHC to complete LTBI treatment would be half of those to find one additional active TB patient (united states dollars,158.6 vs USD 299.7). Considering the current epidemiologic TB situation in Brazil, the enhanced HHC management that would include LTBI investigation beyond active TB case finding would result in 4,001 averted cases utilizing 12% of the Brazilian TB budget. A public health approach with standardized evaluation, local decisions for improvements, followed by intensive initial and in-service training appears promising to scale up LTBI management.

Mycobacterium tuberculosis latency-associated antigen Rv1733c SLP improves the accuracy of differential diagnosis of active tuberculosis and latent tuberculosis infection / 中华医学杂志(英文版)

BACKGROUND@#Differential diagnosis of active tuberculosis (ATB) and latent tuberculosis infection (LTBI) has been a challenge for clinicians in high TB burden countries. The purpose of this study was to improve the accuracy of differential diagnosis of ATB and LTBI by using fluorescent immunospot (FluoroSpot) assay to detect specific Th1 cell immune responses. The novel mycobacterium tuberculosis (MTB) latency-associated antigens Rv1733c and synthetic long peptides derived from Rv1733c (Rv1733c SLP) were used based on virulence factors early secreting antigen target-6 (ESAT-6) and culture filtrate protein-10 (CFP-10).@*METHODS@#Fifty-seven ATB cases, including 20 pathogen-confirmed ATB and 37 clinically diagnosed ATB, and 36 LTBI cases, were enrolled between January and December 2017. FluoroSpot assay was used to detect the interferon γ (IFN-γ) and interleukin 2 (IL-2) secreted by the specific T cells after being stimulated with MTB virulence factors ESAT-6 and CFP-10, MTB latency-associated antigens Rv1733c and Rv1733c SLP. The receiver operating characteristic (ROC) curve was used to define the best cutoff value of latency-associated antigens in the use of differentiating ATB and LTBI. The sensitivity, specificity, predictive value, and likelihood ratio of ESAT-6 and CFP-10-FluoroSpot combined with latency-associated antigen in the differential diagnosis of ATB and LTBI were also calculated.@*RESULTS@#Following the stimulation with Rv1733c and Rv1733c SLP, the frequency of single IL-2-secreting T cells stimulated by Rv1733c SLP had the largest area under the ROC curve, which was 0.766. With a cutoff value of 1 (spot-forming cells [SFCs]/2.5 × 105 peripheral blood mononuclear cells) for frequency, the sensitivity and specificity of distinguishing ATB from LTBI were 72.2% and 73.7%, respectively. ESAT-6 and CFP-10-FluoroSpot detected the frequency and proportion of single IFN-γ-secreting T cells; the sensitivity and specificity of distinguishing ATB from LTBI were 82.5% and 66.7%, respectively. Combined with the frequency of single IL-2-secreting T cells stimulated by Rv1733c SLP on the basis of ESAT-6 and CFP-10-FluoroSpot, the sensitivity and specificity increased to 84.2% and 83.3%, respectively.@*CONCLUSION@#Rv1733c SLP, combined with ESAT-6 and CFP-10, might be used as a candidate antigen for T cell-based tuberculosis diagnostic tests to differentiate ATB from LTBI.

Ankylosing spondylitis and psoriatic arthritis: revisiting screening of latent tuberculosis infection and its follow-up during anti-tumor necrosis factor therapy in an endemic area

OBJECTIVES: To retrospectively evaluate the performance and distinctive pattern of latent tuberculosis (TB) infection (LTBI) screening and treatment in patients with ankylosing spondylitis (AS) and psoriatic arthritis (PsA) under anti-tumor necrosis factor (TNF) therapy and determine the relevance of re-exposure and other risk factors for TB development. METHODS: A total of 135 and 83 patients with AS and PsA, respectively, were evaluated for LTBI treatment before receiving anti-TNF drugs via the tuberculin skin test (TST), chest radiography, and TB exposure history assessment. All subjects were evaluated for TB infection at 3-month intervals. RESULTS: The patients with AS were more often treated for LTBI than were those with PsA (42% versus 30%, p=0.043). The former also presented a higher frequency of TST positivity (93% versus 64%, p=0.002), although they had a lower frequency of exposure history (18% versus 52%, p=0.027) and previous TB (0.7% versus 6%, p=0.03). During follow-up [median, 5.8 years; interquartile range (1QR), 2.2-9.0 years], 11/218 (5%) patients developed active TB (AS, n=7; PsA, n=4). TB re-exposure was the main cause in seven patients (64%) after 12 months of therapy (median, 21.9 months; IQR, 14.2-42.8 months) and five LTBI-negative patients. TB was identified within the first year in four patients (36.3%) (median, 5.3 months; IQR, 1.2-8.8 months), two of whom were LTBI-positive. There was no difference in the TB-free survival according to the anti-TNF drug type/class; neither synthetic drug nor prednisone use was related to TB occurrence (p>0.05). CONCLUSION: Known re-exposure is the most critical factor for incident TB cases in spondyloarthritis. There are also some distinct features in AS and PsA LTBI screening, considering the higher frequency of LTBI and TST positivities in patients with AS. Annual risk reassessment taking into consideration these peculiar features and including the TST should be recommended for patients in endemic countries.

Latent tuberculosis infection in patients with rheumatic diseases / Infecção latente por tuberculose em pacientes com doenças reumatológicas

ABSTRACT Most people infected by Mycobacterium tuberculosis (Mtb) do not have any signs or disease symptoms, a condition known as latent tuberculosis infection (LTBI). The introduction of biological agents, mainly tumor necrosis factor (TNF) inhibitors, for the treatment of immune-mediated diseases such as Rheumatoid Arthritis (RA) and other rheumatic diseases, increased the risk of reactivation of LTBI, leading to development of active TB. Thus, this review will approach the aspects related to LTBI in patients with rheumatologic diseases, especially those using iTNF drugs. For this purpose it will be considered the definition and prevalence of LTBI, mechanisms associated with diseases and medications in use, criteria for screening, diagnosis and treatment. Considering that reactivation of LTBI accounts for a large proportion of the incidence of active TB, adequate diagnosis and treatment are crucial, especially in high-risk groups such as patients with rheumatologic diseases.

RESUMO A maioria das pessoas infectadas por Mycobacterium tuberculosis (Mtb) não possui sinais ou sintomas da doença, quadro conhecido como infecção latente por tuberculose (ILTB). A introdução de agentes biológicos, sobretudo inibidores do fator de necrose tumoral (iTNF), para o tratamento de doenças imunomediadas, como artrite reumatoide (AR) e outras doenças reumatológicas, aumentou o risco de reativação de ILTB, levando ao desenvolvimento de tuberculose (TB) ativa. Assim, esta revisão abordará os aspectos relacionados à ILTB em pacientes com doenças reumatológicas, especialmente naqueles em uso de medicamentos iTNF. Para tanto, serão considerados a definição e a prevalência de ILTB, os mecanismos associados às doenças e às medicações em uso, bem como os critérios para rastreamento, diagnóstico e tratamento da ILTB. Como a reativação da ILTB é responsável pela grande proporção de casos de TB ativa, o diagnóstico e o tratamento adequados são cruciais, principalmente em grupos de alto risco, como os pacientes com doenças reumatológicas.

Neutrophil CD64 expression levels in IGRA-positive individuals distinguish latent tuberculosis from active disease

BACKGROUND CD64 (FcγR1) is a high-affinity receptor for monomeric IgG1 and IgG3. Circulating neutrophils express very low amounts of CD64 on their surface. OBJECTIVES Our primary aim was to investigate the utility of neutrophil CD64 surface expression as a biomarker of active pulmonary tuberculosis (TB). We hypothesised that elevated neutrophil CD64 expression in TB infection would be associated with interferon gamma (IFN-γ) as an inducer of CD64 expression. METHODS The expression level of CD64 per neutrophil (PMN CD64 index) was quantitatively measured with flow cytometry using a Leuko64 kit in samples from patients with TB and latent TB infection (LTBI) as well as healthy controls, as part of a prospective cohort study in Brazil. FINDINGS The PMN CD64 index in patients with TB was higher than that in healthy controls and LTBI. Receiver operating characteristic curve analyses determined that the PMN CD64 index could discriminate patients with TB from those with LTBI and healthy individuals. PMN CD64 index levels returned to baseline levels after treatment. CONCLUSIONS The positive regulation of CD64 expression in circulating neutrophils of patients with active TB could represent an additional biomarker for diagnosis of active TB and could be used for monitoring individuals with LTBI before progression of TB disease.

Evaluation of the transcriptional immune biomarkers in peripheral blood from warao indigenous associate with the infection by mycobacterium tuberculosis

Abstract INTRODUCTION: Biomarkers are critical tools for finding new approaches for controlling the spread of tuberculosis (TB), including for predicting the development of TB therapeutics, vaccines, and diagnostic tools. METHODS: Expression of immune biomarkers was analyzed in peripheral blood cells stimulated and non-stimulated with M. tuberculosis antigens ESAT-6, CFP10 and TB7.7. in Warao indigenous individuals. These biomarkers may be able to differentiate TB states, such as active tuberculosis (ATB) cases and latent tuberculosis infection (LTBI) from non-infected controls (NIC). A real-time reverse transcription polymerase chain reaction (RT-qPCR) assay was performed on 100 blood samples under non-stimulation or direct ex vivo conditions (NS=50) and stimulation conditions (S=50). RESULTS: The findings are shown as the median and interquartile range (IQR) of relative gene expression levels of IFN-γ, CD14, MMP9, CCR5, CCL11, CXCL9/MIG, and uPAR/PLAUR immune biomarkers. MMP9 levels were significantly higher in the LTBI-NS and LTBI-S groups compared with the NIC-NS and NIC-S groups. However, CCR5 levels were significantly lower in the LTBI-S group compared with both NIC-NS and NIC-S groups. CCL11 levels were significantly lower in the LTBI-S group compared with the NIC-NS group. CONCLUSIONS: Preliminary findings showed that MMP9 immune biomarkers separated LTBI indigenous individuals from NIC indigenous individuals, while CCR5, CCL11, CD14, and IFN-γ did not differentiate TB states from NIC. MMP9 may be useful as a potential biomarker for LTBI and new infected case detection among Warao indigenous individuals at high risk of developing the disease. It may also be used to halt the epidemic, which will require further validation in larger studies.

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.

Prevalence of latent Mycobacterium tuberculosis infection in renal transplant recipients / Prevalência da infecção latente por Mycobacterium tuberculosis em transplantados renais

ABSTRACT Objective: To estimate the prevalence of latent Mycobacterium tuberculosis infection (LTBI) in renal transplant recipients and to assess sociodemographic, behavioral, and clinical associations with positive tuberculin skin test (TST) results. Methods: This was a cross-sectional study of patients aged ≥ 18 years who underwent renal transplantation at the Renal Transplant Center of the Federal University of Minas Gerais Hospital das Clínicas, located in the city of Belo Horizonte, Brazil. We included renal transplant recipients who underwent the TST between January 2011 and July 2013. If the result of the first TST was negative, a second TST was administered. Bivariate and multivariate analyses using logistic regression were used to determine factors associated with positive TST results. Results: The sample included 216 patients. The prevalence of LTBI was 18.5%. In the multivariate analysis, history of contact with a tuberculosis case and preserved graft function (estimated glomerular filtration rate ≥ 60 mL/min/1.73 m2) were associated with positive TST results. TST induration increased by 5.8% from the first to the second test, which was considered significant (p = 0.012). Conclusions: The prevalence of LTBI was low in this sample of renal transplant recipients. The TST should be administered if renal graft function is preserved. A second TST should be administered if the first TST is negative.

RESUMO Objetivo: Estimar a prevalência da infecção latente por Mycobacterium tuberculosis (ILTB) em transplantados renais e avaliar as associações sociodemográficas, comportamentais e clínicas com a prova tuberculínica (PT) positiva. Métodos: Estudo transversal, com pacientes com idade ≥ 18 anos, transplantados renais no Centro de Transplante Renal do Hospital das Clínicas da Universidade Federal de Minas Gerais, em Belo Horizonte (MG). Foram incluídos os pacientes submetidos a transplante renal que realizaram a PT no período entre janeiro de 2011 e julho de 2013. Quando o resultado da primeira PT foi negativo, uma segunda PT foi realizada. As análises bivariada e multivariada, por meio de regressão logística, foram utilizadas para determinar os fatores associados com PT positiva. Resultados: A amostra incluiu 216 pacientes. A taxa de prevalência para ILTB foi de 18.5%. Na análise multivariada, história de contato com caso de tuberculose e função do enxerto preservada (taxa de filtração glomerular estimada ≥ 60 ml/min/1,73 m2) foram associadas com PT positiva. O incremento da primeira PT para a segunda PT foi de 5,8%, considerado significante (p = 0,012). Conclusões: A prevalência da ILTB foi baixa nessa amostra de pacientes transplantados renais. A PT deve ser efetuada quando a função do enxerto renal estiver preservada. Uma segunda PT deve ser realizada quando a primeira PT for negativa.

Tuberculosis en otorrinolaringología. Reporte de 3 casos / Tuberculosis in otolaryngology. Report of 3 cases / Tuberculose em otorrinolaringología. Relatório de 3 casos

La tuberculosis extrapulmonar suele ser una presentación poco frecuente. Aunque la vía respiratoria alta es la vía de entrada del Mycobacterium tuberculosis, su afectación es rara (menos del 2%), siendo la localización ótica, laríngea y nasofaríngea de carácter excepcional, pudiéndose presentar tanto de forma primaria como secundaria a una lesión pulmonar. Se describen tres formas de presentación de tuberculosis extrapulmonar, resaltando la importancia de su sospecha clínica; fundamental para el diagnóstico. Se reporta un caso de tuberculosis laríngea como presentación primaria; un caso de tuberculosis faríngea como presentación secundaria y un caso de presentación ótica en un paciente inmunocomprometido. Debido al aumento en los últimos años de esta enfermedad es necesario tenerla presente como diagnóstico diferencial. Se destacan las dificultades en su detección, ya que no existen características exclusivas de la tuberculosis. La importancia del diagnóstico precoz radica en que es una enfermedad con buena evolución si es tratada oportunamente.

Extrapulmonary tuberculosis is usually an uncommon presentation. Although the upper respiratory tract is the entry route of the Mycobacterium tuberculosis, its involvement is rare (less than 2%), being the otic, laryngeal and nasopharyngeal localization exceptional, being able to present both primary and secondary to a lung injury. Three forms of presentation of extrapulmonary tuberculosis are described highlighting the importance of their clinical suspicion; fundamental for the diagnosis. A case of laryngeal tuberculosis is reported as primary presentation; a case of pharyngeal tuberculosis as a secondary presentation and a case of otic presentation in an immunocompromised patient. Due to the increase in recent years of this disease it is necessary to keep it in mind as a differential diagnosis. The difficulties in its detection are highlighted, since there are no exclusive characteristics of tuberculosis. The importance of early diagnosis lies in the fact that it is a disease with good evolution if it is treated opportunely.

A tuberculose extrapulmonar é geralmente uma apresentação incomum. Embora a via aérea superior é o Mycobacterium tuberculosis porta de entrada, o seu envolvimento é rara (menos do que 2%), a localização ótica, da laringe e da nasofaringe excepcional, sendo possível que tanto na forma primária como secundária à lesão do pulmão. Três formas de apresentação da tuberculose extrapulmonar são descritas, destacando a importância de sua suspeita clínica; fundamental para o diagnóstico. Um caso de tuberculose laríngea é relatado como apresentação primária; um caso de tuberculose faríngea como apresentação secundária e um caso de apresentação ótica em paciente imunocomprometido. Devido ao aumento nos últimos anos desta doença é necessário ter isto em mente como um diagnóstico diferencial. As dificuldades em sua detecção são destacadas, uma vez que não existem características exclusivas da tuberculose. A importância do diagnóstico precoce reside no fato de ser uma doença com boa evolução se tratada oportunamente.