Cien años de vacuna BCG / One hundred years of BCG vaccine

Resumen La vacuna BCG fue administrada por primera vez en 1921, en París, a un recién nacido de madre tuberculosa. Entre 1924 y 1960, el Instituto Pasteur entregó cultivos de BCG a más de 50 labora torios de todo el mundo. En 1925, el Dr. Andrés Arena lo introdujo en Argentina, donde se comenzó a producir y aplicar la vacuna a recién nacidos por vía oral. La cepa original sufrió múltiples cambios genéticos que no parecen haber afectado su eficacia protectora, establecida aun sin que se conociera el mecanismo de acción. En Argentina, un estudio (1978-1985) demostró que la BCG previene la TB primaria en general, y en un 100% la meningitis y otras localizaciones extrapulmonares. Su efecto es independiente de las medidas de control de la TB (detección de casos y tratamiento). Además, BCG provee protección inespecífica contra diversas enfermedades infecciosas y se la usa en el tratamiento del cáncer de vejiga. En 2020 ya se habían establecido por lo menos cinco tecnologías para el desarrollo de vacunas anti-TB: vacunas celulares, de subunidades proteicas, de ácidos nucleicos, con vector adenovirus, y con virus influenza recombinante como vector. Actualmente hay más de 20 vacunas candidatas anti-TB en evaluación. La historia enseña, y la pandemia de COVID-19 ha confirmado que la vacunación es un instrumento fundamental para el control de las enfermedades infecciosas. Y hasta que haya disponible otra más eficaz, BCG seguirá figurando en el Calendario de Vacunación Nacional, para ser aplicada al recién nacido.

Abstract The BCG vaccine was given for the first time in 1921, in Paris, to a newborn of a mother with tuberculosis. Between 1924 and 1960, the Pasteur Institute delivered BCG cultures to more than 50 laboratories around the world. In 1925, Dr Andrés Arena introduced the BCG seed to Argentina, where the vaccine began to be produced and applied orally to newborns. The original strain underwent diverse genetic changes in different parts of the world, which did not seem to affect its protective efficacy. In Argentina, a study (1978-1985) showed that BCG prevents primary TB in general, and has 100% ef ficacy in meningitis and other extra-pulmonary TB locations. BCG effect is independent of TB control measures (case detection and treatment). Furthermore, BCG provides nonspecific protection from various infections and is used in the treatment of bladder cancer. By 2020, at least five technologies had already been established for the future development of anti-TB vaccines: cellular vaccines, protein subunits, nucleic acids, with adenovirus vector, and with recombinant influenza virus as a vector. There are currently more than 20 TB vaccine candidates under evaluation. History teaches, and the COVID-19 pandemic has confirmed, that vaccination is a fundamental instrument for the control of infectious diseases. Until a more effective vaccine becomes available, BCG will continue to be included in the Argentine National Vaccination Calendar for application to newborns.

Candidatos vacunales contra Mycobacterium tuberculosis: una actualización del tema / Mycobacterium tuberculosis vaccine candidates: an update on the topic

Fundamento: la eficacia protectora de la actual vacuna contra la tuberculosis, sirve para contrarrestar las formas pulmonares de esta enfermedad, su reactivación resulta variable o poco eficiente, lo cual impone la búsqueda urgente de nuevas alternativas profilácticas contra la enfermedad. El avance en la obtención de vacunas y de nuevas drogas más efectivas, depende en gran medida del conocimiento de las características del microorganismo, así como la respuesta del sistema inmune en función del agente patógeno. Objetivo: realizar una revisión actualizada en bases de datos médicas sobre los candidatos vacunales contra Mycobacterium tuberculosis. Métodos: se realizó una revisión bibliográfica acerca del tema de un total de 60 artículos publicados en bases de datos médicas, se escogieron 38 artículos correspondientes a la última década para conformar la investigación. Se mostraron los temas más usados referentes al agente patógeno, Mycobacterium tuberculosis, candidato vacunal y los mecanismos de acción sobre el sistema inmune. Se profundizó sobre los tipos de vacunas y las potencialidades terapéuticas específicas para el Mycobacterium tuberculosis, además de evaluar la implicación inmunológica con relación al candidato vacunal. Conclusiones: la simulación de la infección y los eventos inmunes que le suceden en el establecimiento de la inmunidad natural sin causar la enfermedad, son condiciones esenciales de una vacuna clásica.

Background: The tuberculosis constitutes a serious sanitary problem. The vaccination is a powerful method to prevent the infections. The effectiveness protector of the current vaccine against the tuberculosis, to counteract the lung forms of this illness and its reactivation, is variable or not very efficient, that which imposes the urgent search of new alternative prophylaxes against this illness. The advance in the obtaining of bovine and of new more effective drugs, it depends in great measure of the knowledge of the characteristics of the microorganism as well as the answer of the immune system in the pathogen agent's function. Objectives: to carry out an up-to-date revision on the Candidates vaccinates them against Mycobacterium tuberculosis. Methods: you real it hoisted a bibliographical revision of a total of 60 published articles, of them 40 articles corresponding to the last decade were chosen to conform the investigation. The relating more used topics were shown to pathogen agent Mycobacterium tuberculosis candidate vacunal and the mechanisms of action on the immune system. It was deepened on the types of vaccine and the therapeutic potentialities, specific for the M. tuberculosis, besides, to evaluate the immunologic implication with relationship to the candidate vacunal. Conclusions: The simulation of the infection and the immune events that happen him in the establish ment of the natural immunity, without causing the illness are essential conditions of a classic vaccine.

Effect ofFeitai capsule combined with mycobacterium vaccae on immune function in elderly patients with pulmonary tuberculosis / 国际中医中药杂志

t=2.331,P=0.022) T cell levels and CD4+/CD8+ ratio (1.1 ± 0.2vs. 0.9 ± 0.2;t=4.488,P<0.001) showed significant difference between post-treatment and pretreatment. CD3+, CD4+, CD8+ T cell levels and CD4+/CD8+ ratio after treatment showed significant different between the two groups (t values were 3.920, 11.966, 5.573, 10.700,P<0.01). After the treatment, the cure rate in treatment group was significantly higher than that in the control group (80%vs. 56%;χ2=5.561,P=0.018). The rates of sputum conversion from positive to negative (72.0%vs. 50.0%;χ2=5.086,P=0.024)and cavity closure (36.0%vs. 16.0%;χ2=5.198,P=0.023) 6 months after treatment in the treatment group were higher than those in the control group.ConclusionFeitai capsule combined with mycobacterium vaccae can significantly improve the immune function in elderly patients with pulmonary tuberculosis.

Tuberculosis, Bacillus Calmette-Guérin (BCG) y vacunas de tuberculosis: análisis de patentes / Tuberculosis, Bacillus Calmette-Guérin (BCG) and tuberculosis vaccines: a patent analysis

La relación de la tuberculosis, el Bacillus Calmette-Guérin y las vacunas de tuberculosis como dominio bajo estudio, parte del hecho de que la única vacuna disponible hoy para prevenir la tuberculosis en humanos es la BCG, y el mejoramiento de ella o el desarrollo de nuevas vacunas es estratégico para el control de esta enfermedad. Este estudio pretende contribuir con estas importantes investigaciones a partir de los estudios patentométricos, y tiene como objetivo realizar un análisis métrico que permita describir la productividad de patentes sobre tuberculosis, Bacillus Calmette-Guérin y vacunas de tuberculosis en un determinado periodo de tiempo. Para el estudio de la productividad se analizó el comportamiento de indicadores temporales y geográficos en el dominio, en el que se utilizaron técnicas y herramientas apropiadas para los documentos de patentes. A la investigación de la tuberculosis como enfermedad infecciosa transmisible se le han dedicado grandes esfuerzos. La tuberculosis fue considerada hasta hace poco un problema de salud de los países en desarrollo, mientras hoy, con la reemergencia de la enfermedad, los países desarrollados han acaparado su investigación; sin embargo, estos esfuerzos no han sido proporcionales con la investigación dedicada a una nueva generación de vacunas contra esta enfermedad y no existen nuevas patentes que lo demuestren...

As an object of study, the relationship between tuberculosis, Bacillus Calmette-Guérin and tuberculosis vaccines starts from the fact that the only vaccine currently available to prevent tuberculosis in humans is BCG, and its improvement or the development of new vaccines is a key strategy to control the disease. The present study intends to make a contribution to such important research from a patent metrics perspective. Its purpose is to conduct a metric analysis allowing to describe the productivity of patents for tuberculosis, Bacillus Calmette-Guérin and tuberculosis vaccines in a given time period. For the productivity study, an analysis was carried out of the behavior of temporal and geographic indicators in the domain, using techniques and tools suitable for patent documents. Research into tuberculosis as an infectious communicable disease has received great attention. Until recently, tuberculosis was considered to be a health problem in the developing world. However, after its re-emergence, research has been mainly conducted in developed countries. But such efforts have not been in proportion to research aimed at developing a new generation of vaccines against the disease, and there are no new patents supporting them...

The Importance of Animal Models in Tuberculosis Vaccine Development

Research, development, and production of vaccines are still highly dependent on the use of animal models in the various evaluation steps. Despite this fact, there are strong interests and ongoing efforts to reduce the use of animals in vaccine development. Tuberculosis vaccine development is one important example of the complexities involved in the use of animal models for the production of new vaccines. This review summarises some of the general aspects related with the use of animals in vaccine research and production, as well as achievements and challenges towards the rational use of animals, particularly in the case of tuberculosis vaccine development.

Tratamento diretamente supervisionado: estratégia para o controle da tuberculose / Directly observed treatment: strategy to tuberculosis control

Em 1991, a Organização Mundial de Saúde (OMS) reconheceu que a persistência da tuberculose era resultado da má administração dos programas de controle, do descuido dos governos, da pobreza, do crescimento populacional e do incremento das migrações. Dessa forma, propôs um novo direcionamento para o controle da tuberculose através do Tratamento Diretamente Supervisionado (Directly Observed Treatment, Short-course - DOTs). O Ministé-rio da Saúde brasileiro incorporou o DOTs ao Programa Nacional de Controle da Tuberculose (PNCT) como estratégia para o alcance das metas de cura, diminuição da taxa de abandono e prevenção do surgimento de bacilos--resistentes. Entretanto, os resultados da implementação do DOTs têm sido diversos entre países e entre regiões de um mesmo país, originando questionamentos sobre a efetividade da supervisão do tratamento. Estudos focados na forma de administração dos medicamentos apresentam resultados desfavoráveis ao DOTs e se contrapõem àqueles que descrevem as mudanças provocadas no controle da doença após a implantação da estratégia como um todo. O PNCT brasileiro, atualmente, tem como objetivo a expansão da cobertura DOTs e busca oferecer e realizar o teste anti-HIV para todos os pacientes maiores de 15 anos. Isso corrobora a persistente orientação da OMS pela adoção do DOTs apesar dos divergentes resultados encontrados ao redor do planeta. A utilização dessa estratégia mostra a importância da participação conjunta dos diferentes atores governamentais e da sociedade civil na diversificação e ampliação do controle da tuberculose e o necessário alcance das metas propostas.

In 1991, the World Health Organization (WHO) has recognized that tuberculosis pandemic was a common result of bad Health System Administration efforts, government careless, poorness, population growth and enhancing migration. WHO has proposed new directions to tuberculosis control through Directly Observed Treatment - Short course Therapy (DOTs). Brazilian Ministry of Health has made DOTs a priority in National Programs for Tuberculosis Control (NPTC) in order to achieve goals for cure and abandon rates and prevention for multi-drug resistant bacilli. DOTs results have been different across countries and regions within the same country all over the world, raising questions about the effectiveness of the supervision of the treatment. Studies focused on medicine administration reached results that have discouraged DOTs adoption. These results contradict the changes promoted by DOTs implementation as a whole Program for disease control. The objectives of Brazilian NPTC include expansion of DOTs program and offer HIV testing for every tuberculosis patient over age 15. This strategy is in accordance with WHO guidance for DOTs adoption despite its diverging results over the planet and shows the importance of the participation of government and society for the achievement of the goals proposed for Tuberculosis Control.