Mycobacterium tuberculosis latent infection in healthcare students: systematic review of prevalence / Infecção latente por Mycobacterium tuberculosis em estudantes da área da saúde: revisão sistemática de prevalência / Infección latente por Mycobacterium tuberculosis en estudiantes de la salud: revisión sistemática de la prevalencia

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.

Isoniazid use, effectiveness, and safety for treatment of latent tuberculosis infection: a systematic review

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.

Fatores associados à Infecção latente pelo Mycobacterium Tuberculosis em Profissionais de Saúde da Atenção Primária / Factors associated with latent Mycobacterium Tuberculosis infection in primary care health professionals / Factores asociados a la Infección Latente por Mycobacterium Tuberculosis en Profesionales de Salud de Atención Primaria

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.

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.

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.

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.

Factors associated with tuberculosis disease in children from a hospital in Western Mexico / Factores asociados con enfermedad tuberculosa en niños de un hospital del occidente de México

Abstract Background: This study aimed to describe the clinical and demographic characteristics of children with confirmed tuberculosis disease and identify associated factors. Methods: We conducted a retrospective and observational study at the Hospital Civil de Guadalajara Dr. Juan I. Menchaca. Inpatient and outpatient children under 18 years of age who were reported to the National Epidemiological Surveillance System (SINAVE, for its Spanish acronym) for suspected tuberculosis and who had molecular or microbiological tests for mycobacteria were included in the study. Multivariate analysis with logistic regression was used to analyze associated factors. Results: One hundred and nine patients under 18 years of age with suspected tuberculosis were included in the study. About 50.5% (55/109) were male, and the median age was 11 years. Tuberculosis was confirmed in 55% (n = 60): 15% (9/60) had a pulmonary infection, and the rest (51/60) had an extrapulmonary infection. The diagnostic tests used were histopathological study (n = 26), expectoration or gastric aspirate stains (n = 17), polymerase chain reaction (n = 12), and cultures (n = 5). Positive purified protein derivative (PPD) or interferon-gamma release assay (IGRA) tests were found in 33.9%. Malnutrition (odds ratio [OR] 15.9, 95% confidence interval [CI]: 2.3-109), and consumption of unpasteurized products (OR 7.45, 95% CI: 1.02-54.3) were associated with tuberculosis disease in children. Conclusions: Malnutrition and consumption of unpasteurized dairy products are associated with tuberculosis.

Resumen Introducción: El objetivo de este estudio fue describir las características clínicas y demográficas de niños con enfermedad tuberculosa confirmada e identificar los factores asociados. Métodos: Se realizó un estudio observacional retrolectivo en el Hospital Civil de Guadalajara Dr. Juan I. Menchaca. Se incluyeron menores de 18 años hospitalizados y ambulatorios que se notificaron al Sistema Nacional de Vigilancia Epidemiológica (SINAVE) por sospecha de tuberculosis y que contaron con pruebas moleculares o microbiológicas para micobacterias. El estudio de los factores asociados se realizó mediante análisis multivariado con regresión logística. Resultados: Se incluyeron en el estudio 109 menores de 18 años con sospecha de tuberculosis. El 50.5% (55/109) fueron de sexo masculino y la mediana de edad fue de 11 años. Se confirmó enfermedad tuberculosa en el 55% (n = 60) de los casos: el 15% (9/60) presentaron infección pulmonar y el resto extrapulmonar. Las pruebas diagnósticas utilizadas fueron el estudio histopatológico (n = 26), tinciones de expectoración o aspirado gástrico (n = 17), reacción en cadena de la polimerasa (n = 12) y cultivos (n= 5). 33.9% de los pacientes presentaron prueba de derivado proteico purificado (PPD) o ensayo de liberación de interferón gamma (IGRA) positiva. Se observó que la desnutrición (razón de momios (RM) 15.9, intervalo de confianza (IC) 95% 2.3 - 109) y el consumo de productos no pasteurizados (RM 7.45, IC 95% 1.02 - 54.3) se asociaron con enfermedad tuberculosa en niños. Conclusiones: La desnutrición y el consumo de lácteos no pasteurizados se asocian con la enfermedad tuberculosa.

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

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

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

Progress on diagnosis and treatment of latent tuberculosis infection / 浙江大学学报·医学版

One fourth of the global population has been infected with Mycobacterium tuberculosis, and about 5%-10% of the infected individuals with latent tuberculosis infection (LTBI) will convert to active tuberculosis (ATB). Correct diagnosis and treatment of LTBI are important in ending the tuberculosis epidemic. Current methods for diagnosing LTBI, such as tuberculin skin test (TST) and interferon-γ release assay (IGRA), have limitations. Some novel biomarkers, such as transcriptome derived host genes in peripheral blood cells, will help to distinguish LTBI from ATB. More emphasis should be placed on surveillance in high-risk groups, including patients with HIV infection, those using biological agents, organ transplant recipients and those in close contact with ATB patients. For those with LTBI, treatment should be based on the risk of progression to ATB and the potential benefit. Prophylactic LTBI regimens include isoniazid monotherapy for 6 or 9 months, rifampicin monotherapy for 4 months, weekly rifapentine plus isoniazid for 3 months (3HP regimen) and daily rifampicin plus isoniazid for 3 months (3HR regimen). The success of the one month rifapentine plus isoniazid daily regimen (1HP regimen) suggests the feasibility of an ultra-short treatment strategy although its efficacy needs further assessment. Prophylactic treatment of LTBI in close contact with MDR-TB patients is another challenge, and the regimens include new anti-tuberculosis drugs such as bedaquiline, delamanid, fluoroquinolone and their combinations, which should be carefully evaluated. This article summarizes the current status of diagnosis and treatment of LTBI and its future development direction.

Percepção e experiência de profissionais da saúde sobre prevenção da tuberculose latente na atenção primária

Objetivo: Analisar a percepção e a experiência de profissionais da saúde sobre prevenção da Infecção Latente por Tuberculose (ILTB) no contexto da Atenção Primária. Material e Método: Estudo exploratório, descritivo, de abordagem qualitativa, realizado com oito profissionais de saúde da atenção primária, de três regiões do Brasil (Centro-Oeste, Sudeste e Sul) e do Distrito Federal. Os dados foram coletados por entrevista coletiva semiestruturada com a questão norteadora: Quais é a percepção e a experiência dos profissionais da atenção primária à saúde na prevenção da Infecção Latente por Tuberculose? Realizou-se análise de conteúdo pela técnica do Discurso do Sujeito Coletivo. Resultados: Agrupamento dos discursos coletivos: 1) experiência e supervisão de tratamento da ILTB para pessoas em situação de vulnerabilidade; 2) cuidados familiares e a importância da Estratégia Saúde da Família no tratamento da ILTB; 3) campanhas de prevenção da ILTB; e 4) fragilidade na integração com serviços especializados e ausência de fluxos assistenciais/linha de cuidado. Conclusão: As ideias do discurso coletivo expressam a necessidade de mudanças na gestão do trabalho em saúde no nível de atenção primária, a fim de potencializar as ações de prevenção e tratamento existentes, considerando a educação permanente, a definição de fluxos assistenciais e de linhas de cuidado, com destaque para a população em situação de vulnerabilidade.

Objective: To analyze the perception and experiences of Primary Health Care professionals regarding the prevention of Latent Tuberculosis Infection (LTBI). Material and Method: Exploratory, descriptive study, with a qualitative approach, carried out with eight primary care health professionals, from three states of Brazil (midwest, southeast and south) and the Federal District. Data were collected through a semi-structured collective interview with the guiding question: What is the perception and experience of primary health care professionals in preventing Latent Tuberculosis Infection? Content analysis was performed using the Collective Subject Discourse technique. Results: Grouping of collective discourses: 1) experience and supervision of LTBI treatment for vulnerable people; 2) Family care and the importance of the Family Health Strategy in the treatment of LTBI; 3) LTBI prevention campaigns and 4) fragility in integration with specialized services and absence of care flows/line of care. Conclusion: The ideas of the collective discourse express the need for changes in the management of health work at the primary care level, in order to enhance existing prevention and treatment actions, considering permanent education, the definition of assistance flows and lines of care, with emphasis on the vulnerable population.

Objetivo: Analizar la percepción y experiencia de los profesionales de la Atención Primaria en Salud sobre la prevención de la Infección de Tuberculosis Latente. Material y Método: Estudio exploratorio, descriptivo, de abordaje cualitativo, realizado con ocho profesionales de salud de la atención primaria, de tres estados de Brasil (centro-oeste, sureste y sur) y del Distrito Federal. Los datos fueron recolectados a través de una entrevista colectiva semiestructurada con la pregunta orientadora: ¿Cuál es la percepción y experiencia de los profesionales de salud de la atención primaria para la prevención de la Infección de Tuberculosis Latente? Se realizó el análisis de contenido mediante la técnica del Discurso del Sujeto Colectivo. Resultados: Agrupación de los discursos colectivos: 1) experiencia y supervisión del tratamiento de la tuberculosis latente para personas vulnerables; 2) Cuidados de la familia y la importancia de la Estrategia de Salud Familiar en el tratamiento de la tuberculosis latente; 3) campañas de prevención de infección de tuberculosis latente y 4) fragilidad para la integración con los servicios especializados y ausencia de líneas de cuidado. Conclusión: El discurso colectivo expresa la necesidad de cambios en la gestión del trabajo en salud en la atención primaria para potenciar acciones de prevención y tratamiento existentes, teniendo en consideración la educación permanente, la definición de líneas asistenciales y de cuidados, con énfasis en la población vulnerable.

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.

Avances en tuberculosis en el 54º congreso chileno de enfermedades respiratorias. 2ª parte: nuevas normas técnicas chilenas para el control y eliminación de la tuberculosis / New Chilean technical standards for the control and elimination of tuberculosis

La incidencia de la tuberculosis (TBC) en Chile se ha ido incrementando en el último quinquenio, excepto al inicio de la pandemia de Covid-19, donde la pesquisa de TBC se redujo en forma importante. El escenario epidemiológico actual dista del objetivo propuesto en la Estrategia Nacional de Salud (ENS) de la década 2011-2020 (un plan nacional de gobierno para enfermedades relevantes en la población) que consistía en alcanzar una tasa de incidencia de todas las formas de TBC menor a 5 / 100.000 habitantes. La nueva ENS para la década 2021-2030 propone reducir la incidencia de la enfermedad mediante el diagnóstico oportuno y precoz focalizando las intervenciones en las poblaciones de riesgo de la enfermedad (grupos vulnerables), a modo de pesquisa activa y no solo como pesquisa por consultas espontáneas de sintomáticos respiratorios, o tamizajes masivos que pueden no seleccionar a la población de riesgo. También propone intervenir en la prevención priorizando el estudio y tratamiento de la población con Infección Tuberculosa Latente (ITL) de mayor riesgo de progresión hacia la enfermedad. Por último, se pretende mejorar la eficiencia del proceso de tratamiento de la TBC, optimizando el acceso y adherencia a las terapias de los casos activos de TBC como medida de incrementar la proporción de curación. Una nueva norma ministerial para el manejo y control de la TBC puede ayudar enormemente a esta propuesta. Esta norma entrada plenamente en vigencia el año 2022 entrega las herramientas operacionales para cumplir el objetivo señalado para la nueva ENS. La norma incorpora actividades tendientes a lograr una mayor cobertura de estudio y tratamiento de la ITL en grupos específicos, donde se incluyen, además de los contactos infantiles, a los contactos adultos y a otros grupos vulnerables. La terapia para esta condición se realizará utilizando la asociación de Isoniazida con Rifapentina de preferencia. Esta terapia se aplica bajo supervisión en una dosis semanal durante 3 meses (12 dosis) y ha demostrado mejor adherencia y menor toxicidad hepática. Para el diagnóstico oportuno de TBC la pesquisa se ha focalizado en los sintomáticos respiratorios (tos con expectoración) de más de 2 semanas en personas que pertenecen a alguno de los grupos vulnerables, o que tienen rasgos clínicos muy sugerentes de la enfermedad (fiebre, sudoración vespertina, hemoptisis, compromiso del estado general). Como herramienta diagnóstica deja de utilizarse la baciloscopía por su baja sensibilidad y es sustituida por pruebas moleculares, siendo la plataforma automatizada de amplificación de ADN del complejo M. tuberculosis más utilizada y disponible en los servicios de salud públicos el GeneXpert MTB/RIF Ultra, que además entrega información de la susceptibilidad a la rifampicina a través de la identificación de una mutación específica del genoma (gen rpoB). Con esta tecnología se agiliza el proceso diagnóstico (puede obtener resultados durante el día de ejecución, habitualmente no demoraría más de 2 horas) y es de alta sensibilidad (sensibilidad muy similar al cultivo). El tratamiento de la TBC sensible a los fármacos del esquema primario (rifampicina = R, isoniazida = H, etambutol = E y pirazinamida = Z) consiste en la administración diaria en la fase inicial (con los 4 fármacos) durante 2 meses y en la fase de continuación (con isoniazida y rifampicina) durante 4 meses, totalmente supervisado. La TBC con resistencia a rifampicina tiene tratamiento con un esquema acortado oral de 9 meses con nuevos fármacos: bedaquilina, linezolid, clofazimina y levofloxacino (6 meses con los 4 fármacos, seguido de 3 meses con clofazimina y levofloxacino). Estas terapias de alta calidad son seguras y prometen mejores resultados de curación. La nueva norma significa una mayor cobertura para la erradicación de los reservorios de la enfermedad y una mayor precisión en el diagnóstico de las fuentes de trasmisión comunitaria de la enfermedad, siendo un aporte significativo hacia la eliminación de la TBC en el país.

The incidence of tuberculosis (TB) in Chile has been increasing in the last five years except at the beginning of the Covid-19 pandemic where TB screening has clearly decreased. The current epidemiological scenario is far from the goal proposed in the National Health Strategy (NHS) of the decade 2011-2020 (a national government plan for relevant diseases in the population) which was to achieve an incidence rate of all forms of TB less than 5/100,000 inhabitants. The new NHS for the decade 2021-2030 proposes to reduce the incidence of the disease through timely and early diagnosis by focusing interventions on populations at risk of the disease (vulnerable groups), as an active screening and not only as screening for spontaneous consultations of respiratory symptomatic or mass screenings that may not select the population at risk. It also proposed to intervene in prevention prioritizing the study and treatment of the population with Latent Tuberculosis Infection (LTI) at higher risk of progression to the disease. Finally, it intends to improve the efficiency of the TB treatment process, optimizing access and adherence to therapies of active TB cases as a measure to increase the cure rate. A new ministerial standard for the management and control of TB can greatly help this proposal. This standard, fully effective in 2022, provides the operational tools to meet the objective set for the new NHS. The standard incorporates activities aimed at achieving greater coverage of study and treatment of LTI in specific groups, which include, in addition to child contacts, adult contacts and other vulnerable groups. Therapy for this condition will be performed using the combination of isoniazid with rifapentine preferably. Therapy is administered under supervision and patients receive therapy once a week for 12 doses for 3 months. This therapy has shown better adherence and lower liver toxicity. For the timely diagnosis of TB, case finding has focused on respiratory symptoms (cough and expectoration) for more than 2 weeks, in individuals that belong to one of the vulnerable groups, or that have additional clinical features very suggestive of the disease (fever, afternoon sweats, hemoptysis, compromise of the general condition). Smear sputum as a diagnostic tool is no longer used due to low sensitivity and it was replaced by molecular tests in automated platform for DNA amplification of the mycobacterium TB complex. The more used and available in public health services is GeneXpert MTB / RIF Ultra, which also provides information on susceptibility to rifampicin through the identification of a specific genome mutation (rpoB gene). With this technology, the diagnostic process is streamlined (you can obtain results during the day of execution, usually it would not take more than 2 hours) and sensitivity is high (sensitivity very similar to culture). Treatment of TB sensitive to first line drugs (rifampicin, isoniazid, ethambutol and pyrazinamide) consists of daily administration in the initial phase (with four drugs) for 2 months and in the continuation phase (with isoniazid and rifampicin) for 4 months, fully supervised. In rifampicin resistant TB, the treatment is a shortened oral regimen of 9 months with new drugs: bedaquiline, linezolid, clofazimine and levofloxacin (six months with four drugs, followed by three months with clofazimine and levofloxacin). These high-quality therapies are safe and promise better healing results. The new national standards mean a greater coverage for the eradication of the reservoirs of the disease and a greater precision in the diagnosis of the sources of community transmission of tuberculosis, being a significant contribution towards the path of control and elimination of TB in the country.

Tuberculosis in children and adolescents with rheumatic diseases using biologic agents: an integrative review / Tuberculose em crianças e adolescentes com doenças reumáticas em uso de medicamentos biológicos: revisão integrativa

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.

QuantiFERON-TB Gold Plus and QuantiFERON-TB Gold In-tube assays for detecting latent tuberculosis infection in Thai healthcare workers

ABSTRACT Detecting latent tuberculosis infection (LTBI) is important, especially in high-risk populations including healthcare workers (HCWs). QuantiFERON-TB Gold Plus (QFT-Plus) is a new version of the interferon-gamma release assays (IGRAs) to replace the QuantiFERON-TB Gold In-tube (QFT-GIT). However, data on the use of QFT-Plus for LTBI detection in high TB-burden countries are limited. This study was conducted in a TB-endemic setting in Thailand. HCWs were enrolled in the study and underwent both tests during the annual health screening. The testing results were compared and the concordance was determined. Of 102 HCWs, 11 (10.78%) were positive according to both tests, and 15 (14.71%) were positive according to QFT-Plus. The overall agreement between assays was 96.08%, with Cohen's kappa coefficient (k) at 0.82. All four discordant results occurred with QFT-GIT negative and QFT-Plus positive. The comparison between QFT-GIT and QFT-Plus based on each antigen tube (TB1 or TB2) exhibited similar concordance with 99.02% and 95.10% agreement, respectively. The intra-comparison between TB1 and TB2 of QFT-Plus also showed good concordance at 96.08%. Among this group of HCWs, the LTBI prevalence of any positive results in both tests was low. Overall, the study showed good agreement between QFT-Plus and QFT-GIT (k = 0.82) with a minimal difference, suggesting similar assay performance to that mainly carried out in TB-low incidence countries. The results support the use of QFT-Plus for detecting LTBI in a format similar to QFT-GIT.

Tuberculosis preventive treatment in children and adolescents: an observational study of secondary data

Abstract Objective To analyze the effectiveness, safety, outcomes, and associated factors of tuberculosis preventive treatment (TPT) in children and adolescents in Paraná, southern Brazil. Method This was an observational cohort study with a retrospective collection of secondary data from the TPT information systems of the state of Paraná from 2009 to 2016, and tuberculosis in Brazil from 2009 to 2018. Results In total, 1,397 people were included. In 95.4% of the individuals, the indication for TPT was a history of patient-index contact with pulmonary tuberculosis. Isoniazid was used in 99.9% of the cases with TPT, and 87.7% completed the treatment. The TPT protection was 98.7%. Among the 18 people who had TB, 14 (77.8%) became ill after the second year of treatment, and four (22.2%) in the first two years (p < 0.001). Adverse events were reported in 3.3% of cases, most of them were gastrointestinal and medication was discontinued in only 2 (0.1%) patients. No risk factors associated with the illness were observed. Conclusions The authors observed a low rate of illness in pragmatics routine conditions in TPT for children and adolescents, especially within the first two years after the end of treatment, with good tolerability and a good percentage of adherence to the treatment. TPT should be encouraged to achieve the goals of the End TB Strategy of the World Health Organization as an essential strategy to reduce the incidence rate of the disease, but studies with new schemes must continue to be carried out in real-life scenarios.

Evaluation of screening methods for the students who had close contact with pulmonary tuberculosis patients in Shanghai / 上海预防医学

ObjectiveTo evaluate the current screening methods for the students who were in close contact with tuberculosis patients， that could accurately identify the preventive treatment subjects， and to improve the tuberculosis prevention and control in Shanghai schools. MethodsThe freshman/sophomore who were in close contact with active tuberculosis patients in the colleges in 2019 were recruited. All the subjects underwent both tuberculin skin test （TST） and QuantiFERON-TB gold in-tube （QFT） test at the enrollment. After signed the informed consent， all of the participants filled in a questionnaire and determined their baseline tuberculosis infection status. They were followed up for 2 years to monitor the conversion of infection status and the incidence of tuberculosis. ResultsFour of 9 （44.4%） positive participants had conversion to negative results， and 5 of 300 （1.7%） negative participants had conversion to positive during the 2-year follow-up， one of which was diagnosed with active tuberculosis. We assessed diagnostic agreement between QFT and TST at different cut-off values. The highest coincidence rate was 94.0% when choosing 15 mm as the cut-off value， with Kappa coefficient of 0.45 （95%CI： 0.32‒0.59）. ConclusionAlthough stricter than the national work requirements， the prevention and control of tuberculosis in Shanghai schools still need to be carried out meticulously. It's necessary to strengthen daily prevention and control measures， and improve the ability of management.

Latent tuberculosis infection status and its risk factors among tuberculosis-related health-care workers in Shanghai / 上海预防医学

ObjectiveTo obtain the status of latent tuberculosis infection （LTBI） among tuberculosis （TB）-related health-care workers （HCWs） in Shanghai， and to explore the risk factors related to TB infection. MethodsA multi-center cross-sectional study was conducted by recruiting medical workers from multiple designated TB hospitals， centers for disease control and prevention， and community health service centers in Shanghai. Each subject was required to complete a questionnaire and to provide a blood sample for TB infection test. Univariate and multivariate analysis ware made in order to find risk factors relating to TB infection. ResultsA total of 165 medical workers were recruited， and the proportion of TB infection was 16.36% （95%CI： 11.49%‒22.76%）. Multivariate logistic analysis showed that clinical doctors and nurses （adjusted OR=9.756， 95%CI： 1.790‒53.188）， laboratory staffs （adjusted OR=78.975， 95%CI： 8.749‒712.918）， and nursing and cleaning workers （adjusted OR=89.920， 95%CI： 3.111‒2 598.930） had higher risk of TB infection. ConclusionThe overall LTBI prevalence among TB-related HCWs is low. However， working as doctors， nurses， laboratory staffs， nursing workers and cleaning workers are risk factors of TB infection. TB-related HCWs who work at hospitals are at risk of TB infection comparing to medical staffs who work outside hospitals.

Strengthening management of latent tuberculosis infection and accelerating the elimination of the tuberculosis epidemic / 上海预防医学

Screening and preventive treatment for latent tuberculosis infection （LTBI） are important measures to reduce the incidence of active tuberculosis （TB） and its global burden. This paper discusses the current status of LTBI prevalence and preventive treatment， risk of incidence in high-risk groups， screening methods， and other interventions， emphasizing the importance of prevention and control as early as possible in a scientific strategy， so as to lay a solid foundation for eliminating TB by 2030.

Latent tuberculosis infection and screening method among close contacts in schools in Xuhui District，Shanghai from 2020 to 2022 / 上海预防医学

ObjectiveTo investigate the latent tuberculosis infection （LTBI） of close contacts in schools of Xuhui District， and to explore the tuberculin skin test （TST）- interferon-γ release assay （IGRA） two-step method in order to discover the screening strategy of tuberculosis in Xuhui District. MethodsClose contacts of tuberculosis in schools of Xuhui District from 2020 to 2022 were selected as research subjects. Screening was conducted using symptom questionnaire， TST， chest X-rays， IGRA， and the information including the etiological results and grade of the index cases， as well as gender， age， and relationship with the index cases of the research subjects were collected. ResultsTotally 615 close contacts of 32 tuberculosis cases occurred in the schools were finally included. Of the 609 close contacts who completed tuberculosis infection screening and underwent TST testing， 153 TST（+） individuals underwent IGRA testing. The final LTBI rate was 4.6%， and the pulmonary tuberculosis detection rate was 163 per 100 000. The relationship with the index cases was an influencing factor for LTBI. The IGRA positivity rate was higher among close contacts with TST ≥15 mm than among those with 10 mm≤ TST <15 mm （χ2=14.41， P<0.05）. ConclusionThe latent tuberculosis infection among close contacts of school tuberculosis cases in Xuhui District remains serious. TST-IGRA two-step method can assist in the accurate diagnosis of LTBI and pulmonary tuberculosis cases.

Novel biomarkers combination in the application of discriminating active tuberculosis and latent tuberculosis infection / 中华传染病杂志

Objective:To evaluate the expressions of three biomarkers combination of CD27, CD38 and human leucocyte antigen (HLA)-DR in the application of discrminating active tuberculosis (ATB) and latent tuberculosis infection (LTBI).Methods:Sixty cases of ATB and 44 cases of LTBI were enrolled from March 2021 to February 2022 in Huashan Hospital, Fudan University and Wuxi Fifth People′s Hospital. Freshly isolated peripheral blood mononuclear cells (PBMC) from patients were stimulated with 6 kDa early secretory antigenic target/culture filtrate protein 10 peptide pools. The expressions of CD27, CD38 and HLA-DR on Mycobacterium tuberculosis-specific CD4 + T lymphocytes were evaluated by polychromatic flow cytometry. Mann-Whitney U test was used for statistical analysis. The area under the receiver operator characteristic curve (AUROC) was used to evaluate the diagnostic value of biomarkers in discriminating ATB and LTBI. Results:The frequencies of CD27 -, CD38 +, HLA-DR +, CD27 -CD38 +, CD27 -HLA-DR + and CD38 + HLA-DR + in ATB group were all higher than those in LTBI group, and the differences were all statistically significant ( U=26.00, 451.00, 384.00, 8.00, 7.00 and 184.00, respectively, all P<0.001). The AUROC of CD27 -CD4 + interferon-γ(IFN-γ) + T lymphocytes was 0.71 with a cut-off value of 52.31%, with the sensitivity of 50.00% and specificity of 87.20%. The AUROC of CD38 + CD4 + IFN-γ + T lymphocytes was 0.82 with a cut-off value of 30.25%, with the sensitivity of 73.40% and specificity of 89.70%. The AUROC of HLA-DR + CD4 + IFN-γ + T lymphocytes was 0.85 with a cut-off value of 36.60%, with the sensitivity of 66.00% and specificity of 94.90%. The AUROC of CD27 -CD38 + CD4 + IFN-γ + T lymphocytes was 0.80 with a cut-off value of 8.82%, with the sensitivity of 90.60% and specificity of 61.50%. The AUROC of CD27 -HLA-DR + CD4 + IFN-γ + T lymphocytes was 0.83 with a cut-off value of 18.62%, with the sensitivity of 75.00% and specificity of 79.50%. The AUROC of CD38 + HLA-DR + CD4 + IFN-γ + T lymphocytes was 0.93 with a cut-off value of 22.35%, with the sensitivity of 79.70% and specificity of 100.00%. Conclusions:The expressions of CD27 -, CD38 + and HLA-DR + in Mycobacterium tuberculosis-specific CD4 + T lymphocytes are higher in ATB group compared to LTBI group. ATB and LTBI could be well discriminated by detecting the expressions of CD27, CD38 and HLA-DR on CD4 + IFN-γ + T lymphocytes with flow cytometry.

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

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

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

To study the prevalence of latent tuberculosis infection among medical students

Background: Risk of developing latent tuberculosis infection increases in medical students with their higher exposure to TB care facilities. Objective: To study the prevalence of latent TB infection among students attending professional degrees MBBS, BDS, MD, MS, MDS at King George’s Medical University, India. Methods: This study was carried out with Tuberculin skin testing among students and active TB cases were excluded. A standard dose of 0.1?mL of purified protein derivative was slowly injected intra dermally into non-dominant forearm. After 48-72 hours, the reaction was estimated by measuring the transverse diameter of the induration. Results: Total 561 students had given consent to get enrolled. Prevalence of latent tuberculosis infection was significant with period of clinical exposure (p-value < 0.05), average size of induration (p-value < 0.001), and history of prior Tuberculin Skin Test (p-value < 0.001). However it was not significant with the age (p-value > 0.05), gender (p-value > 0.05), and history of contact with active cases of TB (p-value > 0.05). Conclusion: The prevalence of latent tuberculosis infection is higher in post graduate students followed by interns and final year students due to more exposure to patients in wards and clinics at King George’s Medical University, India.