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OBJECTIVES: To evaluate the tuberculin skin test (TST) conversion in chronic inflammatory arthropathies (CIA) patients on TNFα inhibitors (TNFi) and without previous latent tuberculosis infection (LTBI) treatment. METHODS: Patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA) with negative LTBI were retrospectively evaluated for TST conversion and active tuberculosis (TB) after six months of exposition to TNFi. Two groups were compared: patients who repeated TST (TST-repetition) during the follow-up and patients who did not (non-TST-repetition). RESULTS: A total of 355 CIA patients on TNFi were screened and 138 (38.9%) did not fulfill the inclusion criteria. Of the remaining 217 CIA patients, 81 (37.3%) repeated TST during TNFi treatment. TST conversion rate was observed in 18 (22.2%) patients without significant differences among CIA (p = 0.578). The number of TB cases was low (n = 10; 4.6%) and was similar in TST-repetition and non-TST-repetition groups [2 (2.5%) vs. 8 (5.9%), p = 0.328]. Of note, 30% of active TB occurred early (6-12 months of TNFi exposure) and the median (full range) time to incident TB was 1.3 (0.6-10.6) years, whereas the median (full range) time to TST repetition was later [3.3 (0.5-13.4) years]. The incidence of active TB was lower among RA patients than AS patients [342 (95% CI 41 - 1446) vs. 1.454 (95% CI 594-2993)/100,000 patient-years, p = 0.049]. CONCLUSION: These results indicate that TST repetition is associated with a high conversion rate, suggesting the need for recommended treatment. The delayed repetition of TST and low number of active TB cases hampered the evaluation of this strategy effectiveness to prevent active infection. Larger studies with systematic repetition patterns are necessary. In addition, the study highlights the need for a greater surveillance for TB in AS patients.
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Artritis Psoriásica , Artritis Reumatoide , Tuberculosis Latente , Espondilitis Anquilosante , Prueba de Tuberculina , Factor de Necrosis Tumoral alfa , Humanos , Estudios Retrospectivos , Artritis Reumatoide/tratamiento farmacológico , Masculino , Femenino , Artritis Psoriásica/tratamiento farmacológico , Persona de Mediana Edad , Espondilitis Anquilosante/tratamiento farmacológico , Tuberculosis Latente/diagnóstico , Tuberculosis Latente/epidemiología , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Adulto , Antirreumáticos/uso terapéutico , Antirreumáticos/efectos adversos , Anciano , Estudios de Cohortes , Enfermedades Endémicas , Inhibidores del Factor de Necrosis Tumoral/uso terapéuticoRESUMEN
OBJECTIVE: To describe the reported cases of newborns subjected to tuberculosis preventive treatment (TPT) in the state of Paraná, Brazil, and to evaluate the safety and effectiveness in preventing the progression of TB disease in this population. METHOD: Observational, descriptive case series, with secondary data. The characteristics of the participants were analyzed from the information systems of preventive treatment of TB (of Paraná), between 2009 and 2016. To evaluate which children had developed tuberculosis later or died, we used the data from the information systems of TB (in Brazil), and mortality (in Paraná), covering the years 2009 to 2018. RESULTS: A total of 24 children underwent TPT with the age at treatment onset ranging from 0 to 87 days (median: 23 days). In 95.8 %, the exposure occurred at home, and in 33.3 % of cases, the mother was the source of the infection. A total of 20.8 % of the children tested positive for tuberculosis test at 3 months of age, 83.3 % completed treatment, and 2 experienced adverse events (gastrointestinal issues). No children developed TB or died during the minimum of a 2-year evaluation period through the official databases. CONCLUSIONS: In this case series, the adherence to the plan was high, with few adverse events and 100 % protection against infection.
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Interferon-gamma (IFN-γ) release assays play a pivotal role in tuberculosis infection (TBI) diagnosis, with QuantiFERON-TB Gold Plus-an enzyme-linked immunosorbent assay (ELISA)-among the most widely utilized. Newer QuantiFERON-TB platforms with shorter turnaround times were recently released. We aimed to evaluate these platforms' agreement in the diagnosis of TBI. Blood samples from a prospective cohort of tuberculosis household contacts were collected at baseline and after 12 weeks of follow-up, and tested with LIAISON, an automated chemiluminescence immunoassay (CLIA) system, QIAreach, a lateral flow (QFT-LF) semi-automated immunoassay, and the ELISA QuantiFERON-TB Gold Plus platform. Test concordances were analyzed. ELISA vs CLIA overall agreement was 83.3% for all tested samples (120/144) [Cohen's kappa coefficient (κ): 0.66 (95% CI: 0.54-0.77)]. Samples positive with CLIA provided consistently higher IFN-γ levels than with ELISA (P < 0.001). Twenty-four (16.7%) discordant pairs were obtained, all CLIA-positive/ELISA-negative: 15 (62.5%) had CLIA IFN-γ levels within borderline values (0.35-0.99 IU/mL) and 9 (37.5%) >0.99 IU/mL. QFT-LF showed only 76.4% (68/89) overall agreement with ELISA [κ: 0.53 (95% CI: 0.37-0.68)] with 21 (23.6%) discordant results obtained, all QFT-LF-positive/ELISA-negative. Overall concordance between ELISA and CLIA platforms was substantial, and only moderate between ELISA and QFT-LF. The CLIA platform yielded higher IFN-γ levels than ELISA, leading to an almost 17% higher positivity rate. The techniques do not seem interchangeable, and validation against other gold standards, such as microbiologically-confirmed tuberculosis disease, is required to determine whether these cases represent true new infections or whether CLIA necessitates a higher cutoff. IMPORTANCE: Tuberculosis is an airborne infectious disease caused by Mycobacterium tuberculosis that affects over 10 million people annually, with over 2 billion people carrying an asymptomatic tuberculosis infection (TBI) worldwide. Currently, TBI diagnosis includes tuberculin skin test and the blood-based interferon-gamma (IFN-γ) release assays, with Qiagen QuantiFERON-TB Gold Plus (QFT) being among those most widely utilized. We evaluated Qiagen's newer QFT platforms commercially available in a prospective cohort of tuberculosis contacts. A substantial agreement was obtained between the current QFT-enzyme-linked immunosorbent assay (ELISA) and the new QFT-chemiluminescence immunoassay (CLIA) platform, although QFT-CLIA provided higher concentrations of IFN-γ, leading to a 16.6% higher positivity rate. We highlight that both platforms may not be directly interchangeable and that further validation is required.
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Ensayo de Inmunoadsorción Enzimática , Ensayos de Liberación de Interferón gamma , Interferón gamma , Mycobacterium tuberculosis , Tuberculosis , Humanos , Estudios Prospectivos , Adulto , Mycobacterium tuberculosis/inmunología , Femenino , Masculino , Ensayos de Liberación de Interferón gamma/métodos , Tuberculosis/diagnóstico , Ensayo de Inmunoadsorción Enzimática/métodos , Persona de Mediana Edad , Interferón gamma/sangre , Adulto Joven , Composición Familiar , Adolescente , Niño , Anciano , Preescolar , Inmunoensayo/métodosRESUMEN
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.
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BACKGROUND: The duration of the protective effect of tuberculosis preventive therapy (TPT) is controversial. Some studies have found that the protective effect of TPT is lost after cessation of therapy among people with human immunodeficiency virus (HIV) in settings with very high tuberculosis incidence, but others have found long-term protection in low-incidence settings. METHODS: We estimated the incidence rate (IR) of new tuberculosis disease for up to 12 years after randomization to 4 months of rifampin or 9 months of isoniazid, among 991 Brazilian participants in a TPT trial in the state of Rio de Janeiro, with an incidence of 68.6/100 000 population in 2022. The adjusted hazard ratios (aHRs) of independent variables for incident tuberculosis were calculated. RESULTS: The overall tuberculosis IR was 1.7 (95% confidence interval [CI], 1.01- 2.7) per 1000 person-years (PY). The tuberculosis IR was higher among those who did not complete TPT than in those who did (2.9 [95% CI, 1.3-5.6] vs 1.1 [.4-2.3] per 1000 PY; IR ratio, 2.7 [1.0-7.2]). The tuberculosis IR was higher within 28 months after randomization (IR, 3.5 [95% CI, 1.6-6.6] vs 1.1 [.5-2.1] per 1000 PY between 28 and 143 months; IR ratio, 3.1 [1.2-8.2]). Treatment noncompletion was the only variable associated with incident tuberculosis (aHR, 3.2 [95% CI, 1.1-9.7]). CONCLUSIONS: In a mostly HIV-noninfected population, a complete course of TPT conferred long-term protection against tuberculosis.
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Antituberculosos , Infecciones por VIH , Isoniazida , Tuberculosis , Humanos , Masculino , Incidencia , Femenino , Tuberculosis/prevención & control , Tuberculosis/epidemiología , Adulto , Antituberculosos/uso terapéutico , Brasil/epidemiología , Isoniazida/uso terapéutico , Infecciones por VIH/epidemiología , Infecciones por VIH/prevención & control , Rifampin/uso terapéutico , Persona de Mediana Edad , Adulto Joven , AdolescenteRESUMEN
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.
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Tuberculosis Latente , Prueba de Tuberculina , Adulto , Humanos , Colombia/epidemiología , Análisis de Costo-Efectividad , Inmunocompetencia , Ensayos de Liberación de Interferón gamma/economía , Ensayos de Liberación de Interferón gamma/métodos , Ensayos de Liberación de Interferón gamma/normas , Tuberculosis Latente/diagnóstico , Tuberculosis Latente/economía , Tuberculosis Latente/epidemiología , Sensibilidad y Especificidad , Prueba de Tuberculina/métodos , Prueba de Tuberculina/economíaRESUMEN
ABSTRACT Objective: The aim of this study was to synthesize the evidence on the prevalence of latent Mycobacterium tuberculosis infection (LTBI) among undergraduate health care students. Methods: A systematic review of prevalence with meta-analysis was conducted. Prospective and retrospective cohorts and cross-sectional studies involving probable exposure to M. tuberculosis during undergraduate education, along with the tuberculin skin test (TST) or interferon-γ release assay (IGRA) for investigation of latent tuberculosis were searched. Searches were conducted in MEDLINE, CINAHL, EMBASE, LILACS, Scopus, and Web of Science databases. Independent reviewers were responsible for the selection and inclusion of studies. Data were extracted, critically appraised, and synthesized using the JBI approach. PRISMA was used to report the study. Results: Twenty-two studies were analyzed. The overall prevalence in healthcare undergraduate students was 12.53%. Conclusion: The prevalence of LTBI in undergraduate health students was high for such a highly educated population. Screening with TST and/or IGRA and chemoprophylaxis, when necessary, should be provided to undergraduate health students when in contact with respiratory symptomatic patients.
RESUMO Objetivo: O objetivo deste estudo foi sintetizar as evidências sobre a prevalência de infecção de Mycobacterium tuberculosis (ILTB) entre estudantes de graduação da área da saúde. Método: Foi realizada uma revisão sistemática de prevalência com metanálise. Coortes prospectivas e retrospectivas e estudos transversais envolvendo provável exposição a M. tuberculosis durante a graduação, juntamente com o teste tuberculínico (TT) ou ensaio de liberação de interferon-γ (IGRA) para investigação de tuberculose latente foram pesquisados. As buscas foram realizadas nas bases de dados MEDLINE, CINAHL, EMBASE, LILACS, Scopus e Web of Science. Revisores independentes foram responsáveis pela seleção e inclusão dos estudos. Os dados foram extraídos, avaliados criticamente e sintetizados utilizando a abordagem JBI. PRISMA foi usado para relatar o estudo. Resultados: Vinte e dois estudos foram analisados. A prevalência geral em estudantes de graduação da área da saúde foi de 12,53%. Conclusão: A prevalência de ILTB em estudantes de graduação em saúde foi alta para uma população com alto nível de escolaridade. Triagem com TT e/ou IGRA e quimioprofilaxia, quando necessária, deve ser fornecida aos estudantes de graduação da área da saúde quando em contato com pacientes sintomáticos respiratórios.
RESUMEN Objetivo: El objetivo de este estudio fue sintetizar la evidencia sobre la prevalencia de infección latente por Mycobacterium tuberculosis (ILTB) entre estudiantes universitarios de la salud. Métodos: Se realizó una revisión sistemática de la prevalencia con metanálisis. Cohortes prospectivas y retrospectivas y estudios transversales que involucran exposición probable a M tuberculosis durante la educación universitaria, junto con la prueba cutánea de tuberculina (TST) o el ensayo de liberación de interferón-γ (IGRA) para la investigación de tuberculosis latente. Las búsquedas se realizaron en las bases de datos MEDLINE, CINAHL, EMBASE, LILACS, Scopus y Web of Science. Revisores independientes fueron responsables de la selección e inclusión de los estudios. Los datos se extrajeron, se evaluaron críticamente y se sintetizaron utilizando el enfoque JBI. Se utilizó PRISMA para informar el estudio. Resultados: Se analizaron veintidós estudios. La prevalencia global en estudiantes universitarios en salud fue del 12,53%. Conclusión: La prevalencia de LTBI en estudiantes universitarios de salud fue alta para una población con un nivel educativo tan alto. Se debe proporcionar tamizaje con TST y/o IGRA y quimioprofilaxis, cuando sea necesario, a los estudiantes universitarios en salud cuando estén en contacto con pacientes sintomáticos respiratorios.
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Humanos , Tuberculosis Latente , Mycobacterium tuberculosis , Estudiantes , Prevalencia , Metaanálisis , Revisión SistemáticaRESUMEN
ABSTRACT Background: The treatment strategy for latent tuberculosis infection is to reduce the number of tuberculosis cases and consequently reduce the transmission of pathogenic bacteria. This study aimed to determine the safety, effectiveness, and adherence of isoniazid use for latent tuberculosis infection treatment. Methods: To identify studies on isoniazid use for latent tuberculosis infection, five electronic databases were searched. The methods and results are presented in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Results: Most studies (53) used isoniazid for 9 months. The prevalence of use and adherence to treatment varied considerably (18% to 100%), and were evaluated by participant completion of isoniazid treatment for latent tuberculosis infection. The adverse events most frequently reported were hepatotoxicity, gastric intolerance, and neuropathy; the rates of occurrence ranged from < 1% to 48%. In the studies that evaluated the effectiveness of isoniazid for latent tuberculosis infection, the rate varied from 0 to 19.7% for patients who did not have active tuberculosis after the follow-up period. Conclusions: The importance of maintaining follow up for patients using isoniazid should be emphasized due to the risk of developing adverse events. Despite the treatment challenges, the rates of patients who used isoniazid and developed active tuberculosis during the follow-up period were low. We believe that isoniazid continues to contribute to tuberculosis control worldwide, and better care strategies are required.
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Resumo Objetivo Avaliar a tuberculose latente entre pessoas vivendo com HIV e contatos de pessoas com tuberculose. Métodos Estudo transversal, quantitativo, realizado no estado do Pará, a partir dos casos de infecção tuberculosa latente notificados entre os anos 2019 e 2020. Os dados foram extraídos do Sistema de Informação de Infecção Latente por Tuberculose, na Secretaria de Estado de Saúde Pública, no período de novembro a dezembro de 2021. Para análise, utilizaram-se a estatística descritiva, o teste qui-quadrado e o teste G, além da razão de prevalência, no Bioestat 5.3, com nível de significância de 5%. Resultados Foram estudados 1.116 casos de tuberculose latente, sendo 653 em 2019 e 463 em 2020. O desfecho indicou baixa proporção de tratamentos completos (n=734). Entre os registros, 371 eram de pessoas vivendo com HIV e 416 contatos de casos de tuberculose. Observou-se associação da infecção latente em pessoas vivendo com HIV e contatos com as variáveis sexo, idade, procedência e situação de encerramento (p<0,0001). Conclusão A tuberculose latente em pessoas vivendo com HIV e contatos apresenta diferentes padrões quando associada ao perfil sociodemográfico, sendo necessário priorizar a identificação desses grupos para a adoção de ações estratégicas que impactem no controle da doença.
Resumen Objetivo Evaluar la tuberculosis latente entre personas que viven con el VIH y los contactos de personas con tuberculosis. Métodos Estudio transversal, cuantitativo, realizado en el estado de Pará, a partir de casos de infección por tuberculosis latente notificados entre los años 2019 y 2020. Los datos se extrajeron del Sistema de Información de Infección por Tuberculosis Latente, de la Secretaría de Salud Pública del Estado de Pará, en noviembre y diciembre de 2021. Para el análisis se utilizó la estadística descriptiva, la prueba ji cuadrado y la prueba G, además de la razón de prevalencia, en Bioestat 5.3, con nivel de significación de 5 %. Resultados Se estudiaron 1.116 casos de tuberculosis latente, de los cuales 653 fueron en 2019 y 463 en 2020. El resultado indicó baja proporción de tratamiento completo (n=734). Entre los registros, 371 eran de personas que viven con el VIH y 416 contactos de casos de tuberculosis. Se observó relación entre la infección latente en personas que viven con el VIH y los contactos, con las variables sexo, edad, procedencia y situación de cierre (p<0,0001). Conclusión La tuberculosis latente en personas que viven con el VIH y contactos presenta diferentes patrones al relacionarla con el perfil sociodemográfico, por lo que es necesario priorizar la identificación de estos grupos para adoptar acciones estratégicas que impacten en el control de la enfermedad.
Abstract Objective To assess latent tuberculosis among people living with HIV and contacts of people with tuberculosis. Methods This is a cross-sectional, quantitative study, carried out in the state of Pará, based on cases of latent tuberculosis infection reported between 2019 and 2020. Data were extracted from the Latent Tuberculosis Infection Information System, at the State Department of Public Health, from November to December 2021. For analysis, descriptive statistics, chi-square test and G test were used, in addition to prevalence ratio, in Bioestat 5.3, with a significance level of 5%. Results A total of 1,116 cases of latent tuberculosis were studied: 653 in 2019 and 463 in 2020. The outcome indicated a low proportion of complete treatments (n=734). Among the records, 371 were of people living with HIV and 416 were of contacts of tuberculosis cases. An association was observed between latent infection in people living with HIV and contacts with the variables sex, age, origin and termination situation (p<0.0001). Conclusion Latent tuberculosis in people living with HIV and contacts presents different patterns when associated with the sociodemographic profile, making it necessary to prioritize the identification of these groups in order to adopt strategic actions that impact disease management.
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ABSTRACT Background: Among chronic condition problems, tuberculosis still represents a serious public health problem globally. Objective: To investigate latent tuberculosis infection in patients with Crohn's disease. Retrospective, descriptive cross-sectional study of quantitative analysis. Methods: The research was conducted on diagnosed cases of Crohn's disease at the University Hospital located in a city in Northeastern Brazil. All cases of patients with Crohn's disease undergoing isoniazid or rifampicin therapy for latent tuberculosis (LTBI) were included in the study. The data obtained were subsequently subjected to statistical analysis using the Statistical Package for the Social Sciences (SPSS) program. Results: We analyzed 235 medical records, and it was observed that 56% were male, with a mean age of 42.7. Among these, 54% declared themselves as brown, 31% had completed high school, and 47% were residents of the city of Teresina. Regarding the clinical and epidemiological characteristics of the studied patients classified as having ILTB, 34% of the medical records were diagnosed by tuberculin test, 48.51% were investigated by x-ray examination, and the recent location affected the colon with 27%. Conclusion: Overall, the health profile of the participants in this study aligns with findings previously established in the literature, particularly studies conducted in other Brazilian states, as well as in other developing countries.
RESUMO Objetivo: Investigar a infecção latente por tuberculose (ILTB) em pacientes com doença de Crohn no período de janeiro de 2005 a dezembro de 2019. Métodos: Estudo retrospectivo, descritivo transversal realizado nos casos diagnosticados de doença de Crohn do hospital universitário em uma cidade do nordeste brasileiro. Foram incluídos todos os casos de pacientes com doença de Crohn em terapia com isoniazida ou rifampicina para tuberculose latente que fazem acompanhamento no HU-UFPI. Os dados sobre doença de Crohn e tuberculose latente foram obtidos do banco de dados que foi solicitado ao HU-UFPI após aprovação da proposta de pesquisa no Comitê de Ética e Pesquisa da UFPI. Foram identificados todos os casos de pacientes com doença de Crohn com ILTB diagnosticados no HU-UFPI. Os dados foram analisados estatisticamente no programa Statistical Package for the Social Sciences-SPSS. Resultados: Foram analisados 235 prontuários, observou-se que 56% eram do sexo masculino, com a média de idade 42,7. 54% se declaravam pardos, 31% tinham o ensino médio completo e 47% residentes na cidade de Teresina. As características clínico-epidemiológicas dos pacientes estudados classificados como portadores de ILTB. 34% dos prontuários tinham diagnóstico pela prova tuberculínica, 48,51% foram investigados através do exame de raio x. Houve dados semelhantes em relação ao comportamento inicial e recente da doença de Cronh sendo 62% e 47% com a doença não estenosante/não penetrante, respectivamente, ao que se refere a localização inicial 31% acometido no colón e íleo terminal/colón, e a localização recente acometido no colón com 27%. Conclusão: Em síntese observou se que, o perfil de saúde dos participantes do presente estudo assemelha-se com os resultados previamente estabelecidos pela literatura, como estudos realizados em outros estados brasileiros e outros países em desenvolvimento. Esse trabalho contribuiu para ampliar o conhecimento sobre a doença de Crohn, bem como propor estratégias na melhoria da investigação do diagnóstico de tuberculose latente e ou doença, porém sugere novos estudos nesta temática em questão.
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ABSTRACT Objective: Many biologic agents cause some degree of immunosuppression, which can increase the risk of reactivation of tuberculosis infection (TBI). This risk is variable between individual biologics. We aimed to assess current (and recommended) clinical practice of TBI screening and treatment among patients initiating treatment with biologic agents. Methods: An online questionnaire was distributed via email to members of the Global Tuberculosis Network and associated professional organisations to seek insights into the screening for and treatment of TBI in patients treated with biologics. Results: A total of 163 respondents in 27 countries answered at least one question. For all biologics described in the questionnaire, respondents advised increasing screening relative to current practice. Observed and supported TBI screening rates in patients treated with TNF-a inhibitors were high, especially for older TNF-a inhibitors. Most participants supported TBI screening in patients treated with B- or T-cell inhibitors but not in those treated with interleukin inhibitors. Guideline awareness was higher for TNF-a inhibitors than for other biologic classes (79% vs. 34%). Conclusions: Although respondents stated that TBI screening rates are lower than what they consider ideal, there was a tendency to recommend TBI screening in patients treated with biologics not known to be associated with an increased risk of TBI. As a result, there is a potential risk of over-screening and over-treatment of TBI, potentially causing harm, in patients treated with biologics other than TNF-a inhibitors. There is a need to research the risk of TBI associated with biologics and for guidelines to address the spectrum of TBI risk across all types of biologics.
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ABSTRACT Objective: To conduct a bibliographic review on tuberculosis (TB) disease in children and adolescents with rheumatic diseases, being managed with biologic therapy. Data source: An integrative review with a search in the U.S. National Library of Medicine and the National Institutes of Health (PubMed) using the following descriptors and Boolean operators: (["tuberculosis"] AND (["children"] OR ["adolescent"]) AND ["rheumatic diseases"] AND (["tumor necrosis factor-alpha"] OR ["etanercept"] OR ["adalimumab"] OR ["infliximab"] OR ["biological drugs"] OR ["rituximab"] OR ["belimumab"] OR ["tocilizumab"] OR ["canakinumab"] OR ["golimumab"] OR ["secukinumab"] OR ["ustekinumab"] OR ["tofacitinib"] OR ["baricitinib"] OR ["anakinra"] OR ["rilonacept"] OR ["abatacept"]), between January 2010 and October 2021. Data synthesis: Thirty-seven articles were included, with the total number of 36,198 patients. There were 81 cases of latent tuberculosis infection (LTBI), 80 cases of pulmonary tuberculosis (PTB), and four of extrapulmonary tuberculosis (EPTB). The main rheumatic disease was juvenile idiopathic arthritis. Among LTBI cases, most were diagnosed at screening and none progressed to TB disease during follow-up. Of the TB cases using biologics, most used tumor necrosis factor-alpha inhibitors (anti-TNFα) drugs. There was only one death. Conclusions: The study revealed a low rate of active TB in pediatric patients using biologic therapy. Screening for LTBI before initiating biologics should be done in all patients, and treatment, in cases of positive screening, plays a critical role in preventing progression to TB disease.
RESUMO Objetivo: Fazer um levantamento bibliográfico referente à tuberculose (TB) em crianças e adolescentes com doenças reumáticas, em uso de imunobiológicos. Fonte de dados: Revisão integrativa com busca na base United States National Library of Medicine (PubMed) utilizando os descritores e operadores booleanos: (["tuberculosis"] AND (["children"] OR ["adolescent"]) AND ["rheumatic diseases"] AND (["tumor necrosis fator-alpha"] OR ["etanercept"] OR ["adalimumab"] OR ["infliximab"] OR ["biological drugs"] OR ["rituximab"] OR ["belimumab"] OR ["tocilizumab"] OR ["canakinumab"] OR ["golimumab"] OR ["secukinumab"] OR ["ustekinumab"] OR ["tofacitinib"] OR ["baricitinib"] OR ["anakinra"] OR ["rilonacept"] OR ["abatacept"]), entre janeiro de 2010 e outubro de 2021. Síntese de dados: Trinta e sete artigos foram incluídos, com o total de 36.198 pacientes. Houve 81 casos de tuberculose latente (ILTB), 80 casos de tuberculose pulmonar (TBP) e quatro casos de tuberculose extrapulmonar (TBEP). A principal doença reumática foi a artrite idiopática juvenil. Entre os casos de ILTB, a maioria foi diagnosticada no rastreio e nenhum evoluiu para a TB. Dos casos de TB em uso de imunobiológicos, a maioria utilizava fármacos antiTNFα. Houve somente um caso de óbito. Conclusões: O estudo demonstrou baixa taxa de TB nos pacientes pediátricos em uso de imunobiológicos. O rastreio para ILTB antes do início da terapia com agentes biológicos deve ser realizado em todos os pacientes, e o tratamento, nos casos de rastreio positivo, é importante para evitar a progressão para TB doença.
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Background: Healthcare workers (HCWs) have a higher risk of latent tuberculosis infection (LTBI) and active tuberculosis than the general population. In HCWs, the risk of tuberculosis infection depends on the local tuberculosis prevalence, HCWs' characteristics, the healthcare facility, and prevention and control measures. We aimed to estimate the prevalence and risk factors for LTBI in HCWs at a northern Peruvian hospital. Methods: This study had two phases: (1) a cross-sectional phase involving recruitment, history taking, and sampling for the Interferon-Gamma Release Assays (IGRA test), and (2) a prospective follow-up of IGRA-positive participants. We enrolled direct and non-direct patient caregivers among HCWs. We defined an LTBI case if the IGRA test was positive and clinical, laboratory, and radiological evaluations for active tuberculosis were negative. Results: We recruited 308 participants between November 2022 and May 2023. The mean age was 38.6 ± 8.3 years. Over 75% of the participants were female. The most common job category was technicians (30.5%), physicians (22.7%), nurses (20.5%), and other HCWs groups (17.5%). Most participants worked in hospital wards (28.2%), diagnostics departments (16.9%), and critical care departments (15.6%). The LTBI prevalence among HCWs was 17.86% (95% CI 13.84-22.70). In multivariate analysis, after adjusting for age, time working in our hospital, and family history of tuberculosis, males had a higher risk of LTBI (aPR 1.69, 95% CI 1.01-2.77) than females. Working for more than 10 years increased the risk of LBTI (aPR 2.4, 95% CI 1.44-3.97) compared to working for ≤10 years. Even further, participants who had worked for more than 20 years had an aPR of 4.31 (95% CI 1.09-13.65) compared to those with ≤10 years. Similarly, occupational exposure increased the risk of LTBI (aPR 2.21, 95% CI 1.27-4.08) compared to those HCWs not occupationally exposed. Conclusion: The LTBI prevalence in HCWs at a northern Peruvian hospital was lower compared to other Peruvian cities. Males, more experienced, and occupational exposed HCWs are at higher risk of LTBI. LTBI prevalence in Peruvian HCWs is still high. More studies are needed to address some aspects this study has not examined.
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Objetivo: Objetivo: analisar na literatura científica os fatores associados à infecção latente pelo Mycobacterium Tuberculosis em profissionais da Atenção Primária à Saúde. Método: revisão integrativa da literatura, com coleta realizada entre novembro e dezembro de 2021. Considerou-se como critérios de inclusão: Estudos primários relacionados à temática e que incluam os seguintes profissionais: enfermeiros, médicos, dentistas, técnicos de enfermagem e técnicos de saúde bucal, sem delimitação temporal e de idiomas. Foram critérios de exclusão: estudos oriundos de opiniões de especialistas, editoriais, trabalhos de conclusão de curso, monografias, dissertações e teses. As bases de dados Biblioteca Virtual de Saúde, Medline, Scopus; Web of Science e Embase foram utilizadas. Resultados: foram selecionados nove estudos, que apresentaram os fatores associados idade, sexo e presença de doenças crônicas, estilo de vida e condições de trabalho. Conclusão: foi possível analisar os fatores associados à ILTB, o que poderá subsidiar a realização de políticas públicas mais assertivas e contribuir para o controle deste agravo(AU)
Objective: to analyze in the scientific literature the factors associated with latent infection by Mycobacterium Tuberculosis in Primary Health Care professionals. Method: integrative review of the literature, with collection carried out between November and December 2021. The inclusion criteria were considered: Primary studies related to the theme and which include the following professionals: nurses, doctors, dentists, nursing technicians and oral health technicians, without time or language limitations. Exclusion criteria were: studies originating from expert opinions, editorials, course completion works, monographs, dissertations and theses. The Virtual Health Library, Medline, Scopus databases; Web of Science and Embase were used. Results: nine studies were selected, which presented factors associated with age, sex and presence of chronic diseases, lifestyle and working conditions. Conclusion: it was possible to analyze the factors associated with LTBI, which could support the implementation of more assertive public policies and contribute to the control of this problem(AU)
Objetivo: analizar en la literatura científica los factores asociados a la infección latente por Mycobacterium Tuberculosis en profesionales de la Atención Primaria de Salud. Método: revisión integradora de la literatura, con recolección realizada entre noviembre y diciembre de 2021. Se consideraron como criterios de inclusión los estudios primarios relacionados con el tema y que incluyan a los siguientes profesionales: enfermeros, médicos, odontólogos, técnicos en enfermería y técnicos en salud bucal, sin limitaciones de tiempo ni de idioma. Los criterios de exclusión fueron: estudios provenientes de opiniones de expertos, editoriales, trabajos de finalización de cursos, monografías, disertaciones y tesis. Se utilizaron para las investigaciones: Biblioteca Virtual de Salud, Medline, Scopus; Web of Science y Embase. Resultados: se seleccionaron nueve estudios que presentaron factores asociados a la edad, sexo y presencia de enfermedades crónicas, estilo de vida y condiciones de trabajo. Conclusión: fue posible analizar los factores asociados a la ITBL, que podrían apoyar la implementación de políticas públicas más asertivas y contribuir al control de este problema(AU)
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Humanos , Masculino , Femenino , Atención Primaria de Salud , Personal de Salud , Tuberculosis Latente , Determinantes Sociales de la Salud , Condiciones de Trabajo , Estilo de Vida , Mycobacterium tuberculosisRESUMEN
Latent tuberculosis infection (LTBI) represents a subclinical, asymptomatic mycobacterial state affecting approximately 25% of the global population. The substantial prevalence of LTBI, combined with the risk of progressing to active tuberculosis, underscores its central role in the increasing incidence of tuberculosis (TB). Accurate identification and timely treatment are vital to contain and reduce the spread of the disease, forming a critical component of the global strategy known as "End TB." This review aims to examine and highlight the most recent scientific evidence related to new diagnostic approaches and emerging therapeutic treatments for LTBI. While prevalent diagnostic methods include the tuberculin skin test (TST) and interferon gamma release assay (IGRA), WHO's approval of two specific IGRAs for Mycobacterium tuberculosis (MTB) marked a significant advancement. However, the need for a specific test with global application viability has propelled research into diagnostic tests based on molecular diagnostics, pulmonary immunity, epigenetics, metabolomics, and a current focus on next-generation MTB antigen-based skin test (TBST). It is within these emerging methods that the potential for accurate distinction between LTBI and active TB has been demonstrated. Therapeutically, in addition to traditional first-line therapies, anti-LTBI drugs, anti-resistant TB drugs, and innovative candidates in preclinical and clinical stages are being explored. Although the advancements are promising, it is crucial to recognize that further research and clinical evidence are needed to solidify the effectiveness and safety of these new approaches, in addition to ensuring access to new drugs and diagnostic methods across all health centers. The fight against TB is evolving with the development of more precise diagnostic tools that differentiate the various stages of the infection and with more effective and targeted treatments. Once consolidated, current advancements have the potential to transform the prevention and treatment landscape of TB, reinforcing the global mission to eradicate this disease.
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Some genetic variations in cytokine genes can alter their expression and influence the evolution of Mycobacterium tuberculosis (Mtb) infection. This study aimed to investigate the association of polymorphisms in cytokine genes and variability in plasma levels of cytokines with the development of tuberculosis (TB) and latent tuberculosis infection (LTBI). Blood samples from 245 patients with TB, 80 with LTBI, and healthy controls (n = 100) were included. Genotyping of the IFNG +874A/T, IL6 -174G/C, IL4 -590C/T, and IL10 -1082A/G polymorphisms was performed by real-time PCR, and cytokine levels were determined by flow cytometry. Higher frequencies of genotypes AA (IFNG +874A/T), GG (IL6 -174G/C), TT (IL4 -590C/T), and GG (IL10 -1082A/G) were associated with an increased risk of TB compared to that of LTBI (p = 0.0027; p = 0.0557; p = 0.0286; p = 0.0361, respectively) and the control (p = <0.0001, p = 0.0021; p = 0.01655; p = 0.0132, respectively). In combination, the A allele for IFNG +874A/T and the T allele for IL4 -590C/T were associated with a higher chance of TB (p = 0.0080; OR = 2.753 and p < 0.0001; OR = 3.273, respectively). The TB group had lower levels of IFN-γ and higher concentrations of IL-6, IL-4, and IL-10. Cytokine levels were different between the genotypes based on the polymorphisms investigated (p < 0.05). The genotype and wild-type allele for IFNG +874A/T and the genotype and polymorphic allele for IL4 -590C/T appear to be more relevant in the context of Mtb infection, which has been associated with the development of TB among individuals infected by the bacillus and with susceptibility to active infection but not with susceptibility to latent infection.
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Tuberculosis Latente , Tuberculosis , Humanos , Citocinas/genética , Tuberculosis Latente/genética , Interleucina-10/genética , Interleucina-6/genética , Brasil , Interleucina-4/genética , Polimorfismo de Nucleótido Simple , Predisposición Genética a la EnfermedadRESUMEN
Is there a CD4+ and CD8+ immunity alteration in patients with pulmonary tuberculosis (TB) and diabetes (DM) that does not recover after antituberculosis treatment? This prospective comparative study evaluated CD4+ and CD8+ lymphocytic subpopulations and antituberculosis antibodies in patients with diabetes and tuberculosis (TB-DM), before and after antituberculosis treatment. CD4+ T cell counts were lower in patients with TB-DM compared to those with only TB or only DM, and these levels remained low even after two months of anti-TB treatment. Regarding the CD8+ T cell analysis, we identified higher blood values in the DM-only group, which may be explained by the high prevalence of latent tuberculosis (LTBI) in patients with DM. IgM antituberculosis antibodies levels were elevated in patients with only TB at baseline, and 2 months post-anti-TB treatment, IgG did not express any relevant alterations. Our results suggest an alteration in CD4+ immunity in patients with TB-DM that did not normalize after antituberculosis treatment.
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Tuberculosis (TB) associated with diabetes mellitus (DM) is a growing problem, particularly in low- and medium-resource countries. We conducted an open-label, parallel-group, randomized, and controlled trial in a tertiary care center in Mexico City to assess TB preventive treatment (TPT) with isoniazid (INH) or rifampicin (RIF) in people with type 2 DM. Participants were assigned six months of INH 300 mg/day plus pyridoxine 75 mg or three months of RIF 600 mg/day. The primary outcomes were adverse events resulting in permanent treatment cessation and considered possibly or probably related to study drugs. We included 130 subjects, 68 randomized to INH and 62 to RIF. We prematurely halted the study based on recommendations of the Adverse Event Safety Panel. There was no difference between arms in the overall frequency of adverse events. However, the INH group had significantly more permanent treatment interruptions due to grade 2 recurrent or grade 3 or 4 hepatoxicity. In comparison, the RIF arm had more treatment interruptions due to grade 3 or 4 gastrointestinal intolerance. TPT using INH or RIF is not safe enough to be considered a universal indication to patients with type 2 DM and TB infection. These results underline the need to search for alternative TB preventions with better safety profiles for type 2 DM patients.
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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.