Avaliação das estratégias de busca ativa de casos de tuberculose / Evaluation of active case-finding strategies for tuberculosis

Introdução - As estratégias de busca ativa de casos (BAC) têm por objetivo aumentar a detecção de casos de tuberculose (TB) e agilizar o início do tratamento adequado. Objetivos - O objetivo geral da tese foi avaliar as estratégias de BAC de casos de TB. Os objetivos específicos foram: (artigo 1) estimar o efeito das estratégias de detecção de casos no prognóstico de paciente com TB; (artigo 2) avaliar o rendimento da investigação de contatos, bem como estimar a probabilidade de os contatos serem submetidos a exame, determinar a prevalência da doença entre os contatos e identificar quais características dos casos índices estariam associadas à infecção entre os contatos; e (artigo 3) investigar a associação entre as estratégias de BAC e a taxa de detecção da TB, e explorar a modificação do seu efeito devido a desigualdades sociais. Métodos - Para responder ao primeiro objetivo foi realizado um estudo de coorte retrospectiva dos casos novos de pacientes diagnosticados com TB. Nesse estudo, foi estimado o impacto das estratégias de detecção de casos de TB sobre o risco de óbito e desfechos desfavoráveis do tratamento, utilizando modelos de regressão logística com efeitos aleatórios a nível municipal. Para o segundo objetivo foi realizado um estudo transversal de base comunitária, no qual, analisou-se todos os contatos de casos novos de pacientes com TB. Uma investigação de contato que resultou na detecção de um novo caso de TB foi designada como um rendimento positivo. Utilizou-se a regressão de Poisson Inflacionada de Zero para estimar a probabilidade de os contatos rastreados serem examinados para TB com base nas características dos casos índices. De acordo com esse modelo, calculou-se pesos amostrais que foram aplicados para obter estimativas ponderadas da prevalência de infecção entre os contatos rastreados e calcular a subnotificação de casos. Além disso, empregou-se a regressão Poisson multinível para avaliar as características dos casos índices associadas ao diagnóstico de TB entre os contatos. Para o terceiro objetivo, mediante um estudo ecológico longitudinal, relacionou-se as taxas de detecção de TB de 5.033 municípios brasileiros com a proporção de equipes da atenção básica (eAB) que relataram realizar estratégias de BAC. Além disso, avaliou-se a modificação de efeito devido à presença de desigualdades sociais, utilizando o modelo de Equações de Estimação Generalizada com distribuição binomial negativa. Resultados - No artigo 1, em comparação com a busca passiva ambulatorial, os pacientes detectados de forma passiva em pronto-socorro e ambiente hospitalar apresentaram maiores chances óbito (Odds Ratio ajustada [OR] 3,69; intervalo de confiança de 95% [IC95%]: 3,47-3,93; e OR 4,47; IC95%: 4,22-4,74, respectivamente) e desfechos desfavoráveis de tratamento (OR 1,92; IC95%: 1,84-1,99; e OR 2,06; IC95%: 1,98-2,14, respectivamente). Em contraste, os pacientes detectados através da BAC na comunidade e investigação de contatos exibiram menores chances de óbito (OR 0,77; IC95%: 0,61-0,97; e OR 0,71; IC95%: 0,54-0,92, respectivamente) e de desfechos desfavoráveis de tratamento (OR 0,85; IC95%: 0,77-0,95; e OR 0,82; IC95%: 0,74-0,91, respectivamente). No artigo 2, dos 186.466 casos índices de TB, 70,3% tiveram uma investigação de contato realizada, totalizando 652.286 contatos rastreados. Desses, 69,2% foram submetidos a exames, resultando em 12.243 novos casos de TB identificados (rendimento de 2,0%). A prevalência ponderada para o total de contatos rastreados foi de 2,8% (IC95%: 2,7%-2,9%) o que sugere uma possível subnotificação de 6.021 (IC95%: 5.269-6.673) casos de TB. As características dos casos índices estiveram associadas a diagnóstico de TB entre seus contatos. No artigo 3, a realização da BAC de TB e de investigação de contatos domiciliares por parte das eAB estiveram associadas a uma maior taxa de deteção de TB. No entanto, observou-se uma redução dessa associação com o aumento do desenvolvimento humano municipal (razão de taxas de incidência ajustada [RTI] para o termo de interação 0,95; IC95%: 0,90-0,98; e RTI 0,93; IC95% 0,89-0,96, respectivamente). Por outro lado, a força da associação foi maior com o aumento da vulnerabilidade social no município (RTI 1,11, IC95%: 1,02-1,22; e RTI 1,17, IC95%: 1,08- 1,27, respectivamente). Conclusões - Pacientes descobertos por estratégias de BAC apresentaram um melhor prognóstico de tratamento quando comparado aos identificados por estratégias de busca passiva. Além disso, a investigação de contatos de casos novos de TB contribuiu para o aumento da taxa de detecção, embora estimemos que quase um terço dos casos de TB entre os contatos de casos índices possam estar sendo subnotificados. Por fim, destacamos que as desigualdades sociais presentes nos municípios brasileiros têm o potencial de modificar o efeito das estratégias de BAC na taxa de detecção da TB.

Introduction - Active case-finding (ACF) strategies aim to enhance the detection of tuberculosis (TB) cases and expedite the initiation of appropriate treatment. Objectives The overall objective of the thesis was to evaluate ACF strategies for TB cases. The specific objectives of the articles were: (Article 1) to estimate the effect of case detection strategies on the prognosis of TB patients; (Article 2) to evaluate the yield of contact investigations, as well as to estimate the probability of contacts being examined, determine the disease prevalence among contacts, and identify which characteristics of index cases are associated with infection among the contacts; and (Article 3) to investigate the association between ACF strategies and the TB detection rate, and explore their effect modification due to social inequalities. Methods - To address the first objective, we conducted a retrospective cohort study of newly diagnosed TB patients. In this study, we estimated the impact of TB case detection strategies on the risk of death and unfavourable treatment outcomes using logistic regression models with random effects at the municipal level. For the second objective, we carried out a community-based cross-sectional study, analysing all contacts of newly diagnosed TB patients. We defined contact investigations that resulted in the detection of a new TB case as a positive yield. We employed Zero-Inflated Poisson regression to estimate the probability that contacts screened during the investigation being examined for TB based on the characteristics of the index cases. Using this model, we calculated sampling weights, which were applied to obtain weighted estimates of infection prevalence among screened contacts and to estimate underreporting of cases. Additionally, we used multilevel Poisson regression to assess the characteristics of index cases associated with TB diagnosis among contacts. For the third objective, through a longitudinal ecological study, we analysed TB detection rates across 5,033 Brazilian municipalities in relation to the proportion of primary care teams (PCTs) that reported conducting ACF strategies. Furthermore, we assessed the effect modification due to social inequalities using a marginal model of Generalised Estimating Equations (GEE) with a negative binomial distribution. Results - In Article 1, compared to passive case-finding (PCF) in outpatient clinics, patients detected in PCF emergency rooms and hospital settings had higher odds of death (adjusted Odds Ratio [OR] 3.69; 95% confidence interval [CI]: 3.47-3.93; and OR 4.47; 95% CI: 4.22-4.74, respectively) and unfavourable treatment outcomes (OR 1.92; 95% CI: 1.84-1.99; and OR 2.06; 95% CI: 1.98-2.14, respectively). In contrast, patients detected through community-based ACF and contact investigation showed lower odds of death (OR 0.77; 95% CI: 0.61-0.97; and OR 0.71; 95% CI: 0.54-0.92, respectively) and unfavourable treatment outcomes (OR 0.85; 95% CI: 0.77-0.95; and OR 0.82; 95% CI: 0.74-0.91, respectively). In Article 2, of the 186,466 index TB cases, 70.3% underwent contact investigation, resulting in 652,286 contacts being traced. Of these, 69.2% were examined, leading to the identification of 12,243 new TB cases (yield of 2.0%). The weighted prevalence for the total screened contacts was 2.8% (95% CI: 2.7%-2.9%), suggesting a potential underreporting of 6,021 (95% CI: 5,269-6,673) TB cases. The characteristics of the index cases were associated with TB diagnosis among their contacts. In Article 3, the implementation of community-based ACF and household contact investigation by PCTs was associated with higher TB detection rates in municipalities. However, we observed a reduction in this association with higher municipal human development (adjusted incidence rate ratio [IRR] for the interaction term 0.95; 95% CI: 0.90-0.98; and IRR 0.93; 95% CI: 0.89-0.96, respectively). Conversely, the strength of the association was greater with increasing social vulnerability in the municipality (IRR 1.11; 95% CI: 1.02-1.22; and IRR 1.17; 95% CI: 1.08-1.27, respectively). Conclusion - Patients detected through ACF strategies showed a better treatment prognosis compared to those identified by PCF methods. Additionally, contact investigation for new TB cases contributed to increased detection rates, although we estimate that nearly one-third of TB cases among contacts of index cases may be underreported. Finally, we highlight that social inequalities in Brazilian municipalities have the potential to modify the effect of ACF strategies on TB detection rates.

Uso profiláctico de antimicrobianos fuera de la práctica quirúrgica y de procedimientos invasivos: bases conceptuales y operativas / Prophylactic use of antimicrobials outside surgical and invasive-procedure settings: conceptual and operational basis

El uso preventivo de antimicrobianos es de larga data y no se restringe a antibacterianos. Lo más consensuado y estructurado es la profilaxis antimicrobiana perioperatoria y ante procedimientos invasivos. Fuera de este contexto hay gran cantidad de situaciones, menos caracterizadas, con riesgo de infecciones en que se usan ampliamente, muchas veces con menor sistematización. Esta presentación presenta las bases conceptuales y operativas de este segundo tipo de profilaxis. Conceptualmente la profilaxis primaria pretende evitar la infección por agente único conocido o variados, por exposición ambiental o susceptibilidad específica de ese hospedero y es implementable antes o después de la exposición. Producida esta infección la meta de la profilaxis secundaria intenta evitar la enfermedad y puede tomar dos modalidades, en infecciones sin evidencias de enfermedad clínica o daños, la profilaxis corresponde a "tratamiento de infección latente" y, si aún en ausencia de manifestaciones clínicas, hay elementos de laboratorio precoces premonitorios de progresión, la profilaxis se denomina "tratamiento anticipatorio". Se presentan operacionalmente y resumidas las situaciones en contexto médico no invasivo con uso potencial preventivo de antimicrobianos en base a agentes posibles, situaciones ambientales de riesgo, vulnerabilidad del hospedero, medicamentos a usar, su duración y efectividad con enfoque mayoritario en medicina de adultos.

Antimicrobial use with preventive purpose probably began shortly after its therapeutic use, especially antibiotics. More consensus and sistematization exist with perioperative and invasive procedures prophylaxis. However, beyond that context, there is great number of non invasive medical situations with high risk of secondary infections either by acquisition of pathogens or activation of latent ones, in which antimicrobials are routinely used with preventive purpose, albeit with less sistematization and consensus. This presentation aims to lay down the conceptual and operational basis for antimicrobial prophylaxis in these settings, whose objective is preventing an infection (primary prophylaxis) by a known or a variety of pathogens, either by person to person transmission, enviromental exposure or particular susceptibility of the host, and can be implemented before or after exposure. If already infected, the antimicrobial prophylaxis goal is to avoid progression to disease (secondary prevention) and may take two conceptual approaches; first, without clinical disease but significant risk of progression, the modality can be called "treatment of latent infection". In the second, also clinically asymptomatic, but with premonitory laboratoy signs of impending progression present, early use of antimicrobial is called "preemptive treatment". This presentation will describe the most frequent medical situations where preventive use of antimicrobials is employed, together with the medications most consensually used, according to the host, the agent(s) and medical situation, with emphasis in adults.

Perguntas e respostas sobre tuberculose para educadores comunitários - Elaboração participativa de material educativo / Questions and answers about tuberculosis for community educators - Participatory development of educational material

Esta cartilha é resultado de um processo de construção participativa de material educativo entre educadores e lideranças comunitárias do Fórum TB/RJ e profissionais de saúde.

Eventos adversos sistémicos post-vacuna BCG. Serie de casos pediátricos / Systemic adverse events post-BCG vaccine. Pediatric case series

La vacuna BCG es clave para el control de la tuberculosis. En ocasiones se observan eventos adversos sistémicos causados por Mycobacterium bovis BCG; usualmente asociados a inmunodeficiencia. Describimos seis casos clínicos de niños vacunados con BCG al nacer, con complicaciones sistémicas post-vacunación. M{ETODO: Revisión de historias clínicas de pacientes con infección por M. bovis BCG atendidos en un hospital pediátrico, entre 2010 y 2019. RESULTADOS: De 400 casos confirmados de infecciones por complejo Mycobacterium tuberculosis; ocho fueron identificados como M. bovis BCG; seis casos correspondieron a eventos adversos sistémicos post-vacuna BCG: dos con lesiones cutáneas a distancia, dos osteomielitis y dos infecciones generalizadas. En cinco de los seis pacientes se detectó una alteración de la respuesta inmune. Un paciente falleció por falla multiorgánica, uno se derivó y cuatro completaron 12 meses de tratamiento: dos meses de isoniacida, rifampicina, etambutol, y moxifloxacina, y 10 meses de isoniacida y rifampicina. Tuvieron buena tolerancia a los medicamentos, sin recaída a los dos años. CONCLUSIÓN: La infección grave por M. bovis BCG es una rara complicación sistémica de la vacunación. Es razonable buscar defectos inmunológicos en los niños que desarrollan este tipo de eventos adversos.

The BCG vaccine is key to tuberculosis control. Systemic adverse events caused by Mycobacterium bovis BCG are occasionally observed; usually associated with immunodeficiency. In this report we describe six cases of children vaccinated with BCG at birth, with post-vaccination systemic complications. METHOD: retrospective review of medical records of patients with M. bovis BCG infection treated in a pediatric hospital between 2010 and 2019. RESULTS: Of 400 confirmed cases of Mycobacterium tuberculosis complex infection, eight identified as M. bovis BCG, six corresponded to systemic adverse events post-BCG vaccine: two distant skin lesions, two osteomyelitis and two generalized infections. An altered immune response was detected in five of the six patients. One patient died of multiorgan failure, one was referred and four completed 12 months of treatment: two months of isoniazid, rifampin, ethambutol, and moxifloxacin, and 10 months of isoniazid and rifampin. They had good tolerance to medications, without relapse at two years. CONCLUSION Serious M. bovis BCG infection is a rare systemic complication of vaccination. It is reasonable to look for immunological defects in children who develop these types of adverse events.

Population-based active screening strategy contributes to the prevention and control of tuberculosis / 浙江大学学报·医学版

Despite the achievements obtained worldwide in the control of tuberculosis in recent years, many countries and regions including China still face challenges such as low diagnosis rate, high missed diagnosis rate, and delayed diagnosis of the disease. The discovery strategy of tuberculosis in China has changed from "active discovery by X-ray examination" to "passive discovery by self-referral due to symptoms", and currently the approach is integrated involving self-referral due to symptoms, active screening, and physical examination. Active screening could help to identify early asymptomatic and untreated cases. With the development of molecular biology and artificial intelligence-assisted diagnosis technology, there are more options for active screening among the large-scale populations. Although the implementation cost of a population-based active screening strategy is high, it has great value in social benefits, and active screening in special populations can obtain better benefits. Active screening of tuberculosis is an important component of the disease control. It is suggested that active screening strategies should be optimized according to the specific conditions of the regions to ultimately ensure the benefit of the tuberculosis control.

Cooperación social y ofertas terapéuticas en la lucha contra la tuberculosis en la Ciudad de México, década de 1940 / Social cooperation and therapeutic offers in the fight against tuberculosis in Mexico City, the 1940s decade

Resumen En México, la decidida y sistemática participación de la sociedad civil en la lucha contra la tuberculosis inició en 1939, al crearse el Comité Nacional de Lucha contra la Tuberculosis. Su plural conformación y las labores que desempeñó le distinguieron de las asociaciones y de ligas antituberculosas creadas en décadas previas en diferentes países de las Américas. En este artículo se presentará un primer acercamiento a la plural conformación de ese organismo y se estudiarán algunas de las acciones que impulsó durante su primera década de funcionamiento, un momento en el que también fue particularmente prolífica la coexistencia de diferentes terapéuticas para tratar a los individuos con esa enfermedad.

Abstract The determined and systematic participation of civil society in the fight against tuberculosis in Mexico began in 1939 when the National Committee for the Fight against Tuberculosis was created. Its plural conformation and tasks distinguished it from the anti-tuberculosis associations and leagues created in previous decades in different countries of the Americas. This article will present a first approach to the plural conformation of this organism and will study some of the actions that it promoted during its first decade of operation, in which the coexistence of different therapeutics to treat individuals was also particularly prolific with that disease.

Questões éticas sobre o tratamento da tuberculose: o Programa Nacional de Controle da Tuberculose do Brasil / Ethical issues about tuberculosis treatment: the Brazilian National Tuberculosis Control Program

A tuberculose (TB) é uma doença infecciosa, causada pelo bacilo Mycobacterium tuberculosis (MTB), que atinge os pulmões durante o contágio inicial e que pode ser transmitida através da tosse, fala ou espirro. A Organização Mundial da Saúde (WHO, 2019) classificou a TB como a principal causa de morte no mundo por único agente etiológico, à frente do Vírus da Imunodeficiência Humana (HIV), sendo ainda considerada como grave problema de Saúde Pública, e declarou, em 1993, a TB como estado de emergência mundial, diante dos altos índices de incidência e mortalidade existentes à época. Em 1999, o Brasil normatizou seu Programa Nacional de Controle da Tuberculose (PNCT) e isso aconteceu diante da permanência do "problema da TB", com índices elevados de abandono do tratamento, redução na taxa de cura e de identificação dos casos. O PNCT introduziu: a extensão da cobertura (com a distribuição de medicamentos gratuitamente), o tratamento diretamente observado (no qual o paciente deve tomar a medicação diante de um agente de saúde) e a busca ativa por pessoas portadoras de infecção latente da TB (ILTB). Há, de fato, questões sociais, políticas e econômicas que ainda influenciam na permanência da TB, considerada como Determinante Social de Saúde (DSS). Contudo, há questões éticas envolvidas na maneira como a TB é abordada pela Saúde Pública, tanto pelo PNCT quanto pela OMS, e que também influenciam nas altas taxas de casos de TB na sociedade e na diferenciação desta sociedade. Mesmo com medicamentos eficazes (incluindo o tratamento da ILTB), a TB permanece como um desafio ético para o governo pois, na prática, foi o governo que permitiu que o indivíduo ficasse doente. O principialismo, por ser uma das referências bioéticas da prática médica no Brasil, será a base dessa reflexão, com o intuito de ajudar na compreensão de como as políticas públicas de saúde são feitas no Brasil e quais devem ser suas prioridades, conciliando os interesses da sociedade e do indivíduo. A comparação com outras realidades que enfrentam o mesmo problema, como a Inglaterra, o debate sobre as justificativas da OMS para sua estratégia pelo Fim da TB e os direitos dos pacientes com TB igualmente contribuirão pela busca de quais são essas questões éticas e como podem colaborar na abordagem e erradicação da TB no mundo, mudando a narrativa e a perspectiva de como "enxergar" a doença e o doente. (AU)

Tuberculosis (TB) is an infectious disease caused by the bacillus Mycobacterium tuberculosis (MTB), which affects the lungs during the initial contagion and can be transmitted through coughing, talking, or sneezing. The World Health Organization (WHO, 2019) classified TB as the leading cause of death in the world by a single etiological agent, ahead of the Human Immunodeficiency Virus (HIV), still being considered a serious Public Health problem and, in 1993, declared TB a global state of emergency, given the high incidence and mortality rates existing at the time. In 1999, Brazil standardized its National Tuberculosis Control Program (PNCT) and this happened in the face of the permanence of the "TB problem", with high rates of treatment abandonment, reduction in the cure rate, and identification of cases. The PNCT introduced: the extension of coverage (with free distribution of medication), directly observed treatment (in which the patient must take the medication in front of a health agent), and the active search for people with latent TB infection (LTBI). There are, in fact, social, political, and economic issues that still influence the permanence of TB, considered a Social Determinant of Health (SDH). However, there are ethical issues involved in the way TB is approached by Public Health, both by the PNCT and the WHO, which also influence the high rates of TB cases in society and the differentiation of this society. Even with effective drugs (including LTBI treatment), TB remains an ethical challenge for the government because, in practice, it was the government that allowed the individual to get sick. Principlism, as one of the bioethical references of medical practice in Brazil, will be the basis of this reflection, to help understand how public health policies are carried out in Brazil and what their priorities should be, reconciling the interests of society and the individual. In comparison with other realities that face the same problem, such as England, the debate on the justifications of the WHO for its End TB Strategy and the rights of patients with TB will also contribute to the search for what these ethical issues are and how they can collaborate in the approach and eradication of TB in the world, changing the narrative and perspective of how to "see" the disease and the sick person. (AU)

Factors of abandonment of tuberculosis treatment in the public health network / Factores de abandono al tratamiento de la tuberculosis en la red pública de salud

ABSTRACT This study determines the factors of abandonment of tuberculosis treatment in the public health network of Cali, Colombia, during years 2016 to 2018. We conducted an operational case-control investigation including 224 patients with tuberculosis (112 abandoned treatment and 112 completed it). We found that treatment abandonment for tuberculosis is driven by factors related to the individuals and health services that facilitate non-adherence and drive them away from the care provided in medical institutions.

RESUMEN Este estudio determina los factores de abandono al tratamiento de la tuberculosis en la red pública de salud de Cali, Colombia, durante los años 2016 a 2018. Se realizó una investigación operativa de casos y controles en la que se incluyeron 224 pacientes con tuberculosis (112 abandonaron el tratamiento y 112 lograron completarlo). Se encuentra que el abandono del tratamiento para la tuberculosis está impulsado por factores relacionados con el individuo y los servicios de salud que facilitan la no adherencia y los alejan de la atención brindada en las instituciones médicas.

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.

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.

Discursos dos gestores relacionados às barreiras de acesso ao diagnóstico e tratamento da tuberculose / Discursos de los gestores relacionados con las barreras de acceso al diagnóstico y tratamiento de la tuberculosis / Discourses of managers related to barriers to access tuberculosis diagnosis and treatment

Objetivo: identificar no discurso dos gestores aspectos relacionados às barreiras de acesso e de tratamento das pessoas com tuberculose em serviços da Atenção Primária à Saúde. Método: trata-se de um estudo qualitativo, contou com a participação de seis gestores coordenadores do programa de controle de tuberculose. A coleta dos dados foi realizada utilizando a entrevista e para análise dos dados foi utilizada a fundamentação teórico-metodológica na Análise de Discurso de matriz francesa. Resultados: barreiras que têm dificultado o acesso dos pacientes são organizacionais, falta de profissional, horário de atendimento, realização de busca ativa, demora na marcação e entrega dos exames. Informação: desconhecimento dos sintomas e estigma. Alem disso, a acessibilidade geográfica que dificulta o deslocamento até os serviços de saúde. Considerações finais: o acesso ao diagnóstico da tuberculose nos serviços da Atenção Primária à Saúde apresenta fragilidades. É necessário conscientizar todos os envolvidos nas ações de cuidado à tuberculose, que voltem seus olhares para o agravo.

Objetivo: identificar en el discurso de los gestores aspectos relacionados a las barreras de acceso y de tratamiento de las personas con tuberculosis en servicios de la Atención Primaria de la Salud. Método: se trata de un estudio cualitativo, contó con la participación de seis gestores coordinadores del programa de control de tuberculosis. La recolección de los datos fue realizada utilizando la entrevista y para análisis de los datos fue utilizada la fundamentación teórico-metodológica en el Análisis de Discurso de matriz francesa. Resultados: barreras que han dificultado el acceso de los pacientes son organizacionales, falta de profesional, horario de atención, realización de búsqueda activa, demora en la cita y entrega de los exámenes. Información: desconocimiento de los síntomas y estigma. Además, la accesibilidad geográfica que dificulta el desplazamiento hacia los servicios de salud. Consideraciones finales: el acceso al diagnóstico de la tuberculosis en los servicios de la Atención Primaria de Salud presenta fragilidades. Es necesario concientizar a todos los involucrados en las acciones de cuidado a la tuberculosis, que vuelvan sus miradas hacia el agravio.

Objective to identify in the discourse of managers aspects related to barriers to access and treatment of people with tuberculosis in Primary Health Care services. Method: this is a qualitative study, with the participation of six coordinating managers of the tuberculosis control program. Data collection was performed using the interview and for data analysis was used the theoretical-methodological basis in French Discourse Analysis. Results: barriers that have hindered the access of patients are organizational, lack of professional, service hours, active search, delay in marking and delivery of tests. Information: lack of awareness of symptoms and stigma. In addition, the geographical accessibility that makes it difficult to move to health services. Final considerations: access to the diagnosis of tuberculosis in Primary Health Care services has weaknesses. It is necessary to make aware all those involved in the actions of care for tuberculosis, to turn their eyes to the aggravation.

Levantamento epidemiológico dos casos de tuberculose no Brasil e ações alternativas para auxiliar no tratamento / Epidemiological survey of tuberculosis cases in Brazil and alternative actions to aid in treatment / Estudio epidemiológico de los casos de tuberculosis en Brasil y acciones alternativas para ayudar al tratamiento

tuberculose é uma das doenças infectocontagiosas de maior importância no Brasil e no mundo. Afeta de forma importante populações em situação de vulnerabilidade social e econômica. O objetivo deste estudo foi realizar um levantamento do número de casos notificados de tuberculose no Brasil nos últimos 10 anos (2011 a 2021), avaliar os fatores que afetam a transmissão, bem como discutir o tratamento padrão e com fitoterápicos. O levantamento epidemiológico dos casos de tuberculose no Brasil de janeiro de 2011 a dezembro de 2021 foi realizado dentre os notificados pelo Sistema de Informação de Agravos de Notificação (SINAN). Os resultados indicaram um aumento linear de casos a partir de 2017 com 90.776 casos diagnosticados, em 2018 (94.720) e 2019 (96.655). Acredita-se que o aumento linear da tuberculose neste período pode estar relacionado principalmente com o aumento da pobreza, contudo o compartilhamento de utensílios durante o uso de narguilé podem representar fatores de risco para tuberculose. Seis plantas medicinais afetam diretamente as micobactérias (Chenopodium ambrosioides, Tetradenia riparia, Physalis angulata, Origanum vulgare, Eucalyptus globulus, Mikania glomerata) e cinco plantas com atividade antibacteriana auxiliam no trato respiratório (Nasturtium officinale, Allium sativum, Schinus terebinthifolius, Adiantum capillus-veneris, Allium cepa). Contudo, a tuberculose é uma doença reemergente sendo necessária a adoção de políticas públicas que intensifiquem e implementem medidas sócio-educativas para a implantação do uso de fitoterápicos como medida complementar.

Tuberculosis is one of the most important infectious diseases in Brazil and worldwide. It significantly affects populations in situations of social and economic vulnerability. This study aimed to survey the number of reported tuberculosis cases in Brazil in the last 10 years (2011 to 2021) to assess the factors that affect the transmission and discuss standard and herbal treatments. The epidemiological survey of tuberculosis cases in Brazil from January 2011 to December 2021 was carried out among those notified by the Notifiable Diseases Information System (SINAN). The results indicated a linear increase in cases from 2017, with 90,776 diagnosed cases, in 2018 (94,720) and 2019 (96,655). It is believed that the linear increase in tuberculosis in this period may be mainly related to the increase in poverty. However, the sharing of utensils during the use of hookah may represent risk factors for tuberculosis. Six medicinal plants directly affect mycobacteria (Chenopodium ambrosioides, Tetradenia riparia, Physalis angulata, Origanum vulgare, Eucalyptus globulus, Mikania glomerata), and five plants with antibacterial activity help in the respiratory tract (Nasturtium officinale, Allium sativum, Schinus terebinthifolius, Adiantum capillus-veneris, Allium cepa). However, tuberculosis is a re-emerging disease, and it is necessary to adopt public policies that intensify and implement socio-educational measures for using herbal medicines as a complementary measure.

La tuberculosis es una de las enfermedades infecciosas más importantes en Brasil y en el mundo. Afecta significativamente a las poblaciones en situación de vulnerabilidad social y económica. El objetivo de este estudio fue realizar una encuesta sobre el número de casos notificados de tuberculosis en Brasil en los últimos 10 años (2011 a 2021), para evaluar los factores que afectan a la transmisión, así como para discutir el tratamiento estándar y con fitoterapias. La encuesta epidemiológica de los casos de tuberculosis en Brasil desde enero de 2011 hasta diciembre de 2021 se realizó entre los notificados por el Sistema de Informação de Agravos de Notificação (SINAN). Los resultados indicaron un aumento lineal de casos desde 2017 con 90.776 casos diagnosticados, en 2018 (94.720) y 2019 (96.655). Se cree que el aumento lineal de la tuberculosis en este periodo puede estar relacionado principalmente con el aumento de la pobreza, aunque el hecho de compartir los utensilios durante el uso de la shisha puede representar factores de riesgo para la tuberculosis. Seis plantas medicinales afectan directamente a las micobacterias (Chenopodium ambrosioides, Tetradenia riparia, Physalis angulata, Origanum vulgare, Eucalyptus globulus, Mikania glomerata) y cinco plantas con actividad antibacteriana ayudan a las vías respiratorias (Nasturtium officinale, Allium sativum, Schinus terebinthifolius, Adiantum capillus-veneris, Allium cepa). Sin embargo, la tuberculosis es una enfermedad reemergente siendo necesaria la adopción de políticas públicas que intensifiquen e implementen medidas socioeducativas para la implementación del uso de fitoterápicos como medida complementaria.

Estudo do perfil epidemiológico da tuberculose na população idosa no estado de São Paulo entre os anos de 2018-2020 / Study of the epidemiological profile of tuberculosis in the elderly population in the state of São Paulo between the years 2018-2020 / Estudio del perfil epidemiológico de la tuberculosis en la población anciana del estado de São Paulo entre los años 2018- 2020

A tuberculose e um doença que causa preocupação para as autoridades de saúde pública. Quando analisamos o envelhecimento da população, os idosos são mais susceptíveis a várias doenças, entre elas a tuberculose. Um dos motivos dessa fragilidade na saúde e devido a sua imunossenescência, além das comorbinadas frequentes nesse grupo etário. Desta forma, objetivou realizar uma pesquisa quantitativa, descritiva, realizada por bases secundárias de dados online, no qual foram utilizados o Serviço de Informação do Sistema Único de Saúde (DATASUS). Na pessquisa, foram inclusas pessoas de ambos os sexos com idade igual ou superior a 60 anos e com diagnóstico de Tuberculose no Estado de São Paulo entre os anos de 2018 a 2020. Nesta pesquisa pode se observar uma elevada ocorrência de tuberculose na população idosa principalmente no sexo masculino. Em relação a faixa etária com maior contaminados pela tuberculose foi entre 60-64 anos já a faixa etária com grande número de óbitos ocorreu 70-79 anos, por causa dessa doença.

Tuberculosis is a disease of concern to public health authorities. When we analyze the aging of the population, the elderly are more susceptible to several diseases, including tuberculosis. One of the reasons for this fragility in health is due to its immunosenescence, in addition to the frequent co-morbidities in this age group. In this way, it aimed to carry out a quantitative, descriptive research, carried out by secondary online databases, in which the Information Service of the Unified Health System (DATASUS) was used. In the research, people of both sexes aged 60 years or older and diagnosed with tuberculosis in the State of São Paulo between the years 2018 to 2020 were included. in male. Regarding the age group with the highest number of tuberculosis infections, it was between 60-64 years old, while the age group with a large number of deaths occurred between 70-79 years old, because of this disease.

La tuberculosis es una enfermedad que preocupa a las autoridades de salud pública. Cuando analizamos el envejecimiento de la población, los ancianos son más susceptibles de padecer diversas enfermedades, entre ellas la tuberculosis. Una de las razones de esta fragilidad en la salud se debe a su inmunosenescencia, además de las frecuentes comorbilidades en este grupo de edad. De esta forma, se pretendía realizar una investigación cuantitativa, descriptiva, realizada por bases secundarias de datos online, en las que se utilizó el Servicio de Información del Sistema Único de Salud (DATASUS). En la investigación se incluyeron personas de ambos sexos con 60 años o más y diagnosticadas de Tuberculosis en el Estado de São Paulo entre los años 2018 y 2020. En esta investigación se puede observar una alta ocurrencia de tuberculosis en la población de edad avanzada, especialmente en los varones. En relación con el grupo de edad con mayor contaminación por tuberculosis fue entre 60-64 años ya el grupo de edad con un gran número de muertes se produjo 70- 79 años, a causa de esta enfermedad.

Tuberculosis: el contrapunto del progreso / Tuberculosis: the counterpoint of progress

Resumen A lo largo de la historia, las enfermedades infecciosas han influido directamente en el desarrollo de la humanidad y en este proceso, la tuberculosis ha tenido un rol protagónico. Esta enfermedad mata más seres humanos que cualquier otra de causa infecciosa y, a pesar de esto, continúa siendo una entidad olvidada y un grave problema de salud pública, sobre todo en las naciones más pobres. La trascendencia de la tuberculosis va más allá del ámbito médico y una visión holística de ella nos permite comprender el grado de desarrollo económico y social de un Estado. Si bien Chile mantenía un programa de control históricamente exitoso, las cifras actuales no son auspiciosas y obligan a analizar el problema desde una mirada multidisciplinaria. Es en este marco que planteamos que el médico clínico, para aportar en el control de la enfermedad, debe poner nuevamente en práctica uno de los principios básicos de la Medicina: la semiología.

Abstract Along history, infectious diseases have had a direct influence in the development of humanity, with tuberculosis showing a leading role. Despite this disease being the main cause of mortality among infectious diseases, it remains neglected and constitutes a serious public health problem, especially among the poorest countries in the world. Tuberculosis greatest importance goes beyond Medicine, and a holistic view of the disease allows us to comprehend the economic and social development of a nation. Despite a historically successful control program in Chile, current figures are not auspicious and force upon us the need to address this problem with a multidisciplinary approach. The medical physician is required to put again into practice the fundamental principle of Medicine, Semiology to contribute to the control of tuberculosis.

Factores asociados a la distribución espacial de la tuberculosis en La Habana, 2015 / Factors associated with the spatial distribution of tuberculosis in Havana, 2015

Introducción: El año 2015 es el marco de referencia temporal internacional para evaluar las acciones de la estrategia Fin a la tuberculosis. La eliminación de la enfermedad como problema de salud requiere de la identificación de poblaciones y territorios en mayor riesgo, y de los determinantes de su distribución geográfica. Objetivo: Determinar la influencia de factores socioeconómicos, demográficos y geoespaciales en la distribución espacial de la tuberculosis en La Habana en el año 2015. Métodos: Se realizó un estudio ecológico. Se describió la distribución espacial del total de casos de tuberculosis, la confección TB/VIH y los casos TB/reclusos a nivel de municipio; así como de variables socioeconómicas, demográficas y geoespaciales con datos disponibles de todos los municipios de la provincia. Se realizaron mapas temáticos para cada una de las variables. Posteriormente, se realizó un análisis de superposición de capas. Resultados: Se observó una mayor concentración de casos en el centro-sur de la provincia; principalmente en los municipios Centro Habana, Habana Vieja, Diez de Octubre y Boyeros, a excepción de este último, estos municipios son los más densamente poblados, los que tienen mayor ocupación del suelo y condiciones de vida más desfavorables. Conclusiones: La distribución espacial de la tuberculosis en La Habana está estrechamente relacionada al comportamiento de variables socioeconómicas, demográficas y geoespaciales en sus diferentes municipios. Estas variables deben ser tomadas en cuenta en intervenciones de salud dirigidas a la eliminación de la enfermedad en la provincia(AU)

Introduction: The year 2015 constitutes the international time frame of reference to evaluate the actions of the End tuberculosis strategy. The elimination of the disease as a health problem requires the identification of populations and territories at greatest risk, and the determinants of their geographical distribution. Objective: Determine the influence of socio-economic, demographic and geospatial factors on the spatial distribution of tuberculosis in Havana in 2015. Methods: An ecological study was conducted. The spatial distribution of total TB cases, TB/HIV and TB/inmate cases at the municipality level was described; as well as socio-economic, demographic and geospatial variables with data available from all municipalities in the province. Thematic maps were made for each of the variables. Subsequently, a layer overlap analysis was performed. Results: A higher concentration of cases was observed in the center-south of the province; mainly in the municipalities of Centro Habana, Habana Vieja, Diez de Octubre and Boyeros ; with the exception of the latter, these municipalities are the most densely populated, those with the highest land occupation and the most unfavorable living conditions. Conclusions: The spatial distribution of tuberculosis in Havana is closely related to the behavior of socio-economic, demographic and geospatial variables in its different municipalities. These variables should be taken into account in health interventions aimed at eliminating the disease in the province(AU)

Impacto sobre la incidencia de la tuberculosis en Cuba, 1994-2015 / Impact on the incidence of tuberculosis in Cuba, 1994-2015

Introducción: La incidencia es fundamental para evaluar la carga de tuberculosis. Objetivo: Valorar el impacto del Programa Nacional de Control de la Tuberculosis en la incidencia de la tuberculosis en Cuba en el periodo 1994-2015. Métodos: Estudio de series temporales de la incidencia de tuberculosis en el periodo 1994-2015. Se estimó la tendencia exponencial y las variaciones de las tendencias de casos nuevos notificados en Cuba y sus provincias; los totales y medias anuales de los periodos 1994-1999, 1999-2015 y 1994-2015. Se calcularon las diferencias absolutas y relativas entre las provincias cubanas desde 1994-2015. Resultados: La tendencia general de la tasa fue descendente. El periodo de 1994-1999 visualizó una reducción de -0,33x100 000(-505 casos) y entre 1999 y 2015 fue de -0,42(-448 casos). La reducción media anual entre 1994-1999 fue de -0,07 y de 1999-2015 fue de -0,03. En 1994, 1999 y 2015 se notificaron 1616 casos (14,7), 1111(10,0) y 651(5,8), respectivamente. En 1994 la mayor tasa correspondió a la provincia de Cienfuegos (23,1) con riesgo atribuible poblacional porcentual del 65,8 por ciento. En 1999 y 2015 las mayores tasas se presentaron en Ciego de Ávila (18,3) y (9,5), respectivamente (riesgo atribuible poblacional porcentual del 60,7 por ciento en 1999 y del 75,8 por ciento en 2015). En 1994 y 1999 todas las provincias tuvieron tasas > 5,0. En 2015, ocho provincias mostraron tasas < 5,0. En 1999 la provincia con mayor variación de su tasa anual fue Cienfuegos (-0,65) y en 2015 Camagüey (-0,73). Conclusiones: El Programa Nacional de Control de la Tuberculosis en Cuba obtuvo hasta el 2015 una discreta disminución sostenida de la incidencia de la enfermedad en el país; pero no es suficiente para lograr su eliminación, por lo que se requieren nuevas intervenciones diferenciadas y priorizadas(AU)

Introduction: Incidence is critical to assess the burden of tuberculosis. Objective: Assess the impact of the National Program of Tuberculosis Control on the incidence of tuberculosis in Cuba in the period 1994-2015. Methods: Study of time series of tuberculosis incidence in the period 1994-2015. The exponential trend and variations in the trends of new cases reported in Cuba and its provinces were estimated; also the annual totals and averages for the periods 1994-1999, 1999-2015 and 1994-2015. The absolute and relative differences between the Cuban provinces from 1994-2015 were calculated. Results: The overall trend of the rate was downward. The period from 1994-1999 had a reduction of -0.33x100 000 (-505 cases) and between 1999 and 2015 it was -0.42 (-448 cases). The average annual reduction between 1994-1999 was -0.07 and from 1999-2015 it was -0.03. In 1994, 1999 and 2015, 1616 cases (14.7), 1111 (10.0) and 651 (5.8) were reported, respectively. In 1994 the highest rate corresponded to the province of Cienfuegos (23.1) with a percentage population attributable risk of 65.8percent. In 1999 and 2015, the highest rates occurred in Ciego de Ávila (18.3) and (9.5), respectively (percentage population attributable risk of 60.7percent in 1999 and 75.8percent in 2015). In 1994 and 1999 all provinces had rates > 5.0. In 2015, eight provinces showed rates < 5.0. In 1999 the province with the greatest variation in its annual rate was Cienfuegos (-0.65) and in 2015 Camagüey (-0.73). Conclusions: The National Program of Tuberculosis Control in Cuba obtained until 2015 a discreet sustained decrease in the incidence of the disease in the country; but it is not enough to achieve its elimination, so new differentiated and prioritized interventions are required(AU)

Tendencias y desigualdades de la tuberculosis en provincias cubanas para potenciar intervenciones diferenciadas / Tuberculosis trends and inequalities in Cuban provinces to promote differentiated interventions

Introducción: El análisis de tendencias y desigualdades en la ocurrencia de la tuberculosis en Cuba resulta importante para realizar intervenciones diferenciadas. Objetivo: Valorar las tendencias y desigualdades del comportamiento de la tuberculosis en las provincias La Habana, Mayabeque y Ciego de Ávila. Métodos: Estudio ecológico de series temporales de las tasas de notificaciones de tuberculosis en el periodo 2009-2017. Se utilizó la base de datos de vigilancia de tuberculosis del Ministerio de Salud Pública. Se analizaron las tendencias de las tasas de notificación en periodos trienales mediante regresión lineal simple. Se calcularon variaciones totales y anuales de las tasas, proporciones de tuberculosis por trienios en personas con VIH y privados de libertad, medias geométricas y desigualdades de las tasas. Se categorizaron las provincias y municipios según metas hacia la eliminación de la enfermedad. Resultados: La tendencia en Mayabeque y La Habana fue ascendente, la variación total fue del 70,0 por ciento y del 9,0 por ciento, respectivamente. Ciego de Ávila mostró valores relativos dos veces más que Cuba. En La Habana predominaron personas con VIH (38 por ciento); en Mayabeque se incrementaron los dos grupos vulnerables, mientras que en Ciego de Ávila fueron los privados de libertad. La Habana y Mayabeque categorizaron en ultra control avanzado; Ciego de Ávila en control satisfactorio consolidado; del total de los 36 municipios estudiados, 8 (22,2 por ciento) se encontraban en ultracontrol muy avanzado y ninguno en preeliminación. Conclusiones: Los resultados sobre la tendencia de las tasas de tuberculosis y sus desigualdades en las tres provincias sugieren la realización de intervenciones diferenciadas para avanzar hacia la eliminación de esta enfermedad(AU)

Introduction: The analysis of trends and inequalities in the occurrence of tuberculosis in Cuba is important for differentiated interventions. Objective: Assess the trends and inequalities of tuberculosis in the provinces of Havana, Mayabeque and Ciego de Ávila. Methods: Ecological study of time series of tuberculosis. notification rates in the period 2009-2017. The Tuberculosis surveillance database of the Ministry of Public Health was used. Trends in reporting rates in triennial periods were analyzed using simple linear regression. The following were calculated: total and annual variations in rates, proportions of tuberculosis by triennium in people with HIV and deprived of liberty, geometric means and inequalities of rates. The provinces and municipalities were categorized according to goals towards the elimination of the disease. Results: The trend in Mayabeque and Havana was upward, the total variation was 70.0percent and 9.0percent, respectively. Ciego de Ávila showed relative values twice as much as Cuba. In Havana, people with HIV predominated (38percent); in Mayabeque the two vulnerable groups increased, while in Ciego de Ávila they were those deprived of liberty. Havana and Mayabeque categorized in advanced ultra control; Ciego de Ávila in consolidated satisfactory control; of the total of the 36 municipalities studied, 8 (22.2percent) were in very advanced ultracontrol and none in pre-elimination. Conclusions: The results obtained on the trend of tuberculosis rates and their inequalities in the three provinces suggest the realization of differentiated interventions to advance towards the elimination of this disease(AU)

Estratificación espacial de la tuberculosis en menores de 15 años de edad en las provincias occidentales de Cuba, 2011-2015 / Spatial stratification of tuberculosis in the western provinces of Cuba, 2011-2015 in children under 15 years

Introducción: La tuberculosis infantil posee baja incidencia en Cuba, no obstante, se considera un indicador de transmisión reciente de la enfermedad. Objetivo: Estratificar espacialmente la tuberculosis en menores de 15 años de edad en la región occidental de Cuba en el periodo 2011-2015, según las metas progresivas hacia la eliminación de la enfermedad. Métodos: Se realizó un estudio ecológico de series temporales. La estatificación espacial de la tuberculosis se realizó a partir de técnicas geoespaciales que asignan a cada territorio valores ponderados graduados con respecto a los rangos establecidos de las medias geométricas de las tasas de notificación en el periodo. Los estratos se corresponden con las metas progresivas hacia la eliminación de la tuberculosis. Resultados: Se encontraron en la categoría de ultracontrol muy avanzado las provincias La Habana [municipios Plaza de la Revolución (2,4), Centro Habana (3,7), San Miguel del Padrón (2,1), Diez de Octubre (1,6) y Marianao (1,0)], Mayabeque [Melena del Sur (3,5) y San José de las Lajas (1,4)] y Matanzas [Unión de Reyes (1,1)]. Conclusiones: La presencia de diferentes estratos geoespaciales de la tuberculosis en menores de 15 años de edad en la región occidental de Cuba constata la necesidad de diseñar estrategias que se adecuen a la realidad de los diferentes territorios. El abordaje geoespacial fortalece la estratificación epidemiológica de acuerdo a las metas progresivas hacia la eliminación de la tuberculosis(AU)

Introduction: Children tuberculosis has a low incidence in Cuba, however, it is considered an indicator of recent transmission of the disease. Objective: Spatially stratify tuberculosis in children under 15 years of age in the western region of Cuba in the period 2011-2015, according to the progressive goals towards the elimination of the disease. Methods: An ecological time series study was conducted. The spatial stratification of tuberculosis was carried out from geospatial techniques that assign to each territory weighted values graded with respect to the established ranges of the geometric means of the notification rates in the period. The strata correspond to the progressive goals towards the elimination of tuberculosis. Results: The provinces of Havana [municipalities : Plaza de la Revolución (2.4), Centro Habana (3.7), San Miguel del Padrón (2.1), Diez de Octubre (1.6) and Marianao (1.0)], Mayabeque (municipalities : Melena del Sur (3.5) and San José de las Lajas (1.4)] and Matanzas [municipalities : Unión de Reyes (1.1)] were found in the category of very advanced ultracontrol. Conclusions: The presence of different geospatial strata of tuberculosis in children under 15 years of age in the western region of Cuba confirms the need to design strategies that adapt to the reality of the different territories. The geospatial approach strengthens the epidemiological stratification according to the progressive goals towards the elimination of tuberculosis(AU)

Heparin-binding hemagglutinin as a composition antigen of tuberculosis vaccine exerts protective immune effects by inducing IL-17 / 中华预防医学杂志

To explore the protective immune effect induced by mucosal delivery heparin-binding hemagglutinin (HBHA)-a candidate vaccine antigen of Mycobacterium tuberculosis. Female C57BL/6 mice were between 6 and 8 weeks of age before experimental use. Thirty mice received different immunization strategies and were randomly divided into the control group, the early secreting antigen target-6 (ESAT-6) intranasal immunization group, the HBHA intranasal immunization group, the BCG priming PBS control group, or BCG priming HBHA boost group, 6 mice in each group. In order to analyzed the immune effect, the concentrations of plasma Interleukin-17A (IL-17A) and other cytokines were measured by ELISA. Quantitative real-time PCR analyses were performed to detect the relative quantity (RQ) mRNA of IL-17A in the lung. The lung tissue sections were stained to detect the formation of the tertiary lymphoid structures. The chemokines contributed to formation of the tertiary lymphoid structures were also measured. Flow cytometry was used to detect the frequency of Th1 and Th17 cells in the system. Sixty mice in the BCG priming PBS control group and the BCG priming HBHA boost group were sacrificed at different time points after infection to count the lung bacterial burden. The concentrations of plasma IL-17A and relative quantity of lung IL-17A mRNA were highest in the BCG priming HBHA boost group [(14.76±4.73) pg/mL,RQ (12.27±6.71)], which was significantly higher than the control group [(5.57±2.95) pg/mL,RQ (1.30±0.97)] (t=4.213, P<0.001; t=5.984, P<0.001), and also significantly higher than the BCG priming PBS control group [(6.81±2.18) pg/mL,RQ (1.44±1.16)] (t=3.646 P=0.001; t=6.185 P<0.001). Compared with the BCG priming PBS control group (0.38±0.38)% the frequency of spleen Th17 cells were also significantly increased (t=-0.280 , P=0.048) in the BCG-primary HBHA boost group (1.02±0.34)%. In addition, HBHA boosting could promote better formation of the tertiary lymphoid structures in the lung, and decrease the bacterial load on the early stage after BCG challenge. Collectively, mucosal delivery of HBHA can effectively enhance the protective effect after BCG vaccination, and it is a potential candidate vaccine component.

Repurposing of Metformin for the prevention and treatment of Tuberculosis

Abstract The bidirectional relationship between tuberculosis (TB) and diabetes mellitus (DM) is a major concern for medical professionals and epidemiologists as DM affects the severity, progress and outcome of TB and vice versa. Patients affected with TB have a higher rate of morbidity, treatment failure and mortality. Likewise, DM triples the risk of contracting TB and therefore poses a threat to the progress made in the reduction of TB incidence. Hence, it is pivotal to address both the diseases keeping in mind the each other. It is known that adjunct therapy with immunomodulatory drugs can enhance TB immunity among diabetic patients. Metformin, a commonly used anti-diabetic drug with adenosine monophosphate-activated protein kinase (AMPK) activation property, has shown the capacity to reduce the growth of Mycobacterium tuberculosis within the cell. This drug inhibits the mitochondrial complex and possesses anti-inflammatory action. Therefore, Metformin can be considered as an ideal molecule for host-directed or host-targeted therapy for TB.