Progress in research on novel BC adjuvant system / 中国生物制品学杂志

@#Vaccines with novel adjuvants have been listed abroad,while in China,except for aluminum adjuvants widely used in vaccine research and production,few other novel adjuvants have been successfully listed. This paper briefly summarized the source,development history,research progress on biological activity and immune mechanism as well as safety evaluation of the novel BC adjuvant system with independent intellectual property right which has been applied to the vaccine in clinical research stage,so as to provide theoretical support for selection of the adjuvant in the development of novel vaccine.

Vacunación de BCG en el medio rural y la importancia del conocimiento de sus beneficios / BCG vaccination in rural areas and the importance of knowledge of its benefits

Objetivo General: Establecer nivel de conocimiento sobre tuberculosis y vacuna, BCG., de padres y representantes, en Ambulatorio Gabriel Trompiz, Tucacas, Estado Falcón. Metodología: Es un estudio descriptivo de tipo transversal, con una muestra poblacional de 180 madres, padres y representantes entre octubre y diciembre de 2022. Se utilizaron encuestas, formularios elaborados y validados en estudios anteriores; la información fue procesada con el programa estadístico Microsoft Excel. Resultados: la mayor parte de la población respondió que la tuberculosis es una enfermedad producida por un virus, con respecto a la importancia de las inmunizaciones, un 20% desconocía la importancia de la vacunación. El 77% conocían información básica acerca de la vacuna BCG. En cuanto a las enfermedades prevenibles por esta vacuna, un 54% respondió que se trataba sobre la tuberculosis, mientras que casi la mitad de la población estudiada tenía la creencia que tenía que ver con el resfriado común. El 72% de la población considera que la fiebre es una contraindicación para la aplicación de la vacuna BCG. Se demostró que existía una gran desinformación con respecto a la vacunación en la población infantil en el medio rural venezolano(AU)

To establish the level of knowledge about tuberculosis and BCG vaccine., of parents and representatives in the Gabriel Trompiz outpatient clinic, Tucacas, Falcon State. Methodology: it is a descriptive cross-sectional study, with a population sample of 180 mothers, fathers and representatives between October and December 2022. Surveys, forms prepared and validated in previous studies were used, the information was processedwith the Microsoft Excel statistical program. Results: most of the population answered that tuberculosis was a disease caused by a virus, regarding the importance of immunizations, 20% were unaware of the importance of vaccination. 77% knew basic information about the BCG vaccine. Regarding the diseases preventable by this vaccine, 54% answered that it was about tuberculosis, while almost half of the population studied believed that it had to do with the common cold. 72% of the population considers that fever is a contraindication for the application of the BCG vaccine. It was demonstrated that there was a great amount of misinformation regarding vaccination in the child population in rural Venezuela(AU)

Cardiorespiratory Adverse Events after First Vaccination in Preterm Neonates With Gestational Age ?30 Weeks

Objectives: To document the adverse cardiorespiratory events following first routine immunization in preterm neonates. Methods: We retrieved records of neonates with gestational age ?30 weeks, and included those who developed cardiorespiratory events after first vaccines before discharge. Our Unit’s protocol is to administer Bacillus Calmette-Guerin (BCG), hepatitis B vaccine to those discharged at <8 weeks postnatal age. Hexavalent, BCG, pneumococcal vaccine and rotavirus vaccines are given at 8 weeks of age, if hospital stay is predicted to be longer. Unit compliance to vaccination administration at appropriate ages were also measured. Results: Data of 161 neonates ?30 weeks (17.4% <27 week) who completed care in the unit was studied. Cardio-respiratory adverse events were reported in 21(13.7%). None of these required initiation of invasive ventilation. High flow nasal cannula therapy and caffeine restart were required for these events in 14 (9.3%) and 6 (3.9%) neonates, respectively. Lower gestational age, bronchopulmonary dysplasia and sepsis were significant risk factors on univariate analysis. On multivariate analysis, continued need for respiratory support at 4 weeks of age (P=aOR 14.5 (95% CI 5-59.1) was the only independent risk factor for post-vaccination cardiorespiratory adverse events. Of 38 who were not vaccinated at recommended ages by unit policy, 25 were missed opportunities, the rest were deemed unstable for vaccinations at that age by the clinical team. Conclusion: Adverse cardiorespiratory events were uncommon after first vaccinations in very preterm neonates. Administering vaccines in this group before discharge would allow monitoring for these events, especially for those who require long-term respiratory support.

Implications of the non-specific effect induced by Bacillus Calmette-Guerin (BCG) vaccine on vaccine recommendations

Abstract Objectives: Since the beginning of its use for the prevention of tuberculosis (TB) in 1921, other uses of BCG (Bacillus Calmette-Guérin) have been proposed, particularly in the treatment of malignant solid tumors, multiple sclerosis, and other autoimmune diseases. Its beneficial impact on other infections, by nontuberculous mycobacteria, and by viruses, has been more often studied in recent years, especially after the introduction of the concept of trained immunity. The present study's objective was to review the possible indications of BCG and the immunological rationale for these indications. Data source: Non-systematic review carried out in the PubMed, SciELO and Google Scholar databases, using the following search terms: "BCG" and "history", "efficacy", "use", "cancer", "trained immunity", "other infections", "autoimmune diseases". Data synthesis: There is epidemiological evidence that BCG can reduce overall child morbidity/mortality beyond what would be expected from TB control. BCG is able to promote cross-immunity with nontuberculous mycobacteria and other bacteria. BCG promotes in vitro changes that increase innate immune response to other infections, mainly viral ones, through mechanisms known as trained immunity. Effects on cancer, except bladder cancer, and on autoimmune and allergic diseases are debatable. Conclusions: Despite evidence obtained from in vitro studies, and some epidemiological and clinical evidence, more robust evidence of in vivo efficacy is still needed to justify the use of BCG in clinical practice, in addition to what is recommended by the National Immunization Program for TB prevention and bladder cancer treatment.

Revisiting the Chingleput BCG vaccination trial for the impact of BCG revaccination on the incidence of tuberculosis disease

Background & objectives: Vaccines play a crucial role in the prevention of tuberculosis (TB). Revaccination with Bacille Calmette–Guerin (BCG) for the prevention of TB is an important strategy that is currently gaining interest. The objective of this study was to reanalyze the community-based Chingleput BCG vaccination trial for protective efficacy of BCG revaccination against incident TB disease. Methods: A retrospective analysis of the Chingleput BCG vaccination trial (conducted in 1968) data was carried out. Data on participants with evidence of prior BCG vaccination at trial intake and randomized to BCG vaccine [low dose (0.01 mg), high dose (0.1 mg)] and placebo arms were analyzed. The incidence of TB disease, which was based on sputum culture and/or chest X-ray was compared between the BCG and placebo arms over a 15 yr follow up period. Results: Of the 269,727 individuals randomized in the trial; 263,158 had no evidence of TB at baseline, of which 4436 (1.68%) had evidence of BCG vaccination at trial intake (2890 in the BCG vaccine and 1546 in the placebo arms, respectively). There were 77 (190 per 100,000) and 64 (296 per 100,000) incident TB cases in the BCG and placebo arm, respectively, at 15 yr post-vaccination. The incidence of TB disease was significantly lower in the BCG arm [Hazard ratio of BCG arm (95% confidence interval): 0.64 (0.46-0.89)]. Interpretation & conclusions: Retrospective data analysis of this community-based trial revealed that BCG revaccination in a community offered modest protection against the development of TB disease at the end of 15 years which, however, requires further evaluation.

Eventos adversos sistémicos post-vacuna BCG. Serie de casos pediátricos

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. Método: 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.

Differences in responses to the intracellular macrophage environment between Mycobacterium bovis BCG vaccine strains Moreau and Pasteur

BACKGROUND The Bacille Calmette-Guérin (BCG) vaccine comprises a family of strains with variable protective efficacy against pulmonary tuberculosis (TB) and leprosy, partly due to genetic differences between strains. OBJECTIVES Previous data highlighting differences between the genomes and proteomic profiles of BCG strains Moreau and Pasteur led us to evaluate their behaviour in the macrophage microenvironment, capable of stimulating molecular responses that can impact the protective effect of the vaccine. METHODS Strain infectivity, viability, co-localisation with acidified vesicles, macrophage secretion of IL-1 and MCP-1 and lipid droplet biogenesis were evaluated after infection. FINDINGS We found that BCG Moreau is internalised more efficiently, with significantly better intracellular survival up to 96 h p.i., whereas more BCG Pasteur bacilli were found co-localised in acidified vesicles up to 6 h p.i. IL-1β and MCP-1 secretion and lipid droplet biogenesis by infected macrophages were more prominent in response to BCG Pasteur. MAIN CONCLUSION Overall, our results show that, compared to Pasteur, BCG Moreau has increased fitness and better endurance in the harsh intracellular environment, also regulating anti-microbial responses (lower IL-1b and MCP-1). These findings contribute to the understanding of the physiology of BCG Moreau and Pasteur in response to the intraphagosomal environment in a THP-1 macrophage model.

Advances in Bacillus Calmette-Guerin / 中国生物制品学杂志

@#Tuberculosis(TB) is a chronic and debilitating infectious disease caused by Mycobacterium tuberculosis(Mtb). It is a significant health concern that poses a serious threat to human well-being. Bacillus Calmette-Guerin(BCG)is the only approved vaccine for the prevention of TB. BCG is made from attenuated bovine Mtb and is highly effective in preventing tuberculous meningitis and granulomatous TB,which are particularly lethal in infants. However,BCG provides limited protection in both children and adults,and this protective effect decreases over time. Currently,there are ongoing improvements being made to BCG,which involve modifications in immunization routes and procedures. Additionally,researchers are working on the development of new TB vaccines. BCG is primarily used for the prevention of TB and the treatment of bladder cancer,although it also has other indications. This paper reviewed the recent research progress of BCG,focusing on its development history,improvements,and indications.

Protective effects of BCG / 公共卫生与预防医学

BCG vaccine is one of the most widely used vaccines in human history, with tens of billions of doses administered annually over the past century as an important means of preventing tuberculosis. However, BCG is also used for non-traditional purposes of prevention and treatment, such as bladder cancer immunotherapy. In addition to cancer immunotherapy, BCG is increasingly found to be helpful for a variety of immune diseases, including multiple sclerosis, typeⅠdiabetes, and some atopic diseases. It also can protect against non-tuberculous mycobacterium infections, viral infections and even COVID-19. This allogenic protective effect lies in the BCG vaccine's ability to alter immune set points through allogenic T cell immunity, as well as in the epigenetic and immunological effects of metabolomic changes in innate immune cells, a process known as “training immunity”. This paper summarizes the anti-TB effect of BCG and focuses on its heterologous protection and related mechanism.

Genome sequencing and analysis of BCG strain for vaccine production in China / 上海预防医学

ObjectiveTo conduct the sequencing and preliminarily analysis of the whole genome of BCG Shanghai D2PB302 strain （hereinafter referred to as BCG Shanghai D2 strain）， which has been used exclusively for the vaccine production in China. MethodsThe DNA of of BCG Shanghai D2 strain （D2-JIA12-1） was extracted， and the whole genome was sequenced by Pacbio-RS Ⅱ. The sequence data was assembled by Smrtlink and polished with the illumina data. Genes， tRNA and rRNA were predicted based on the sequence data. The functional annotation of predicted genes was performed through BLASTP. The IVE-TB antigen gene and MTBVAC were selected as the target sequences to be compared with Mycobacterium tuberculosis H37Rv （NC_000962.3）. ResultsThe sequence length of BCG Shanghai D2 strain was 4 045 232 bp， and the GC content was 65.66%. A total of 4 259 protein-encoding genes were predicted， with an average gene size of 933 bp. 2 476 genes had biological functions and others were hypothetical proteins.144 virulence genes were obtained by comparing with the VFDB. There were 29 type Ⅶ secretion system genes and 10 PE/PPE protein family genes. ConclusionThe whole genome sequence of BCG Shanghai D2 strain is clarified. It lays a broad foundation for subsequent detection of the stability of major antigen genes.

Coinfección por helmintos y Mycobacteriumtuberculosis

Introducción: Las infecciones por helmintos y Mycobacterium tuberculosis se superponen geográficamente, en particular en los países de ingresos económicos bajos y medianos, donde son altamente endémicas. En estos, la mayoría de las personas se infectan crónicamente por uno o ambos tipos de patógenos en etapas tempranas de sus vidas. Objetivo: Incursionar en los principales aspectos inmunológicos de la coinfección helmintos-M. tuberculosis y sus consecuencias para la progresión de la infección por M. tuberculosis y la vacunación contra la tuberculosis. Métodos: Revisión de artículos sobre inmunología, diagnóstico, tratamiento y control de las infecciones por helmintos y M. tuberculosis publicados entre 2010-2022 en las bases de datos PubMed, Medline y Google Scholar. Se consultaron, además, algunas monografías y artículos originales fechados con anterioridad. Análisis y síntesis de la información: Durante la infección crónica por helmintos, la modulación de las respuestas inmunitarias Th2 y Tregs por parte de esos parásitos podría inhibir las respuestas inmunitarias Th1 y Th17 contra la infección por M. tuberculosis y conducir a su progresión desde la fase latente, de escasa expresión clínica, hasta la fase activa de la tuberculosis. La modulación inmune de los helmintos podría dar lugar a una respuesta deficiente a la vacunación con BCG. Resultados epidemiológicos demuestran que la inmunomodulación podría revertirse mediante tratamientos antihelmínticos. Conclusiones: En la infección crónica por helmintos, es importante considerar que la modulación de sus respuestas inmunitarias activa circuitos inmunorreguladores complejos que pueden conducir a formas graves de la tuberculosis en el hospedero y a respuesta deficiente a la vacunación con BCG.

Introduction: Helminth and Mycobacterium tuberculosis infections overlap geographically, particularly in low- and middle-income countries, where they are highly endemic. There, most people are chronically infected by one or both types of pathogens early in their lives. Objective: To explore the main immunological aspects of helminth-M tuberculosis coinfection and its consequences for the progression of M. tuberculosis infection and vaccination against tuberculosis. Methods: A review of articles on immunology, diagnosis, treatment, and control of helminth and M. tuberculosis infections was conducted on those published between 2010-2022 in PubMed, Medline, and Google Scholar databases. In addition, some previously dated original monographs and articles were consulted. Analysis and synthesis of information: During chronic helminth infection, modulation of Th2 and Treg immune responses by these parasites could inhibit Th1 and Th17 immune responses against M. tuberculosis infection and lead to its progression from the latent phase, with little clinical expression, to the active phase of tuberculosis. Immune modulation of helminths could lead to poor response to BCG vaccination. Epidemiological results show that immunomodulation could be reversed by anthelmintic treatments. Conclusions: In chronic helminth infection, it is important to consider that the modulation of their immune responses activates complex immunoregulatory circuits that can lead to severe forms of tuberculosis in the host and poor response to BCG vaccination.

Does BCG Or MMR Or Routine Vaccination Coverage Protect Against COVID Infection And Mortality In India?

Background: The routine vaccinations and acquired immunity by other viral infections were believed to be acting as a protective factor against severe COVID-19 outbreaks in some countries. Objective: This study is overviewing the relationship of routine BCG, MMR vaccinations and reported MMR disease outbreak with reported COVID-19 infection across the Indian states. Methods: The data on vaccination coverage and respiratory disease infection was obtained from Univer-sal immunization program and Integrated disease surveillance project reports. Spearman rank correla-tion has been used to assess the relationship of routine vaccination and COVID-19 infection. Results: The result did not find any relationship of routine vaccination with BCG and MMR or exposure to MMR infection on COVID-19 infections in India. Conclusion: The exposure to BCG or MMR vaccination did not have a non-specific protection against COVID-19 infection. The results imply that a larger proportion of the Indian population is still vulnerable to COVID-19 infection.

Producción de vacunas en el antiguo Instituto Bacteriológico de Chile

Se relata el nacimiento, auge y decadencia, de la producción de vacunas en el antiguo Instituto Bacteriológico de Chile, desde su fundación en 1929 hasta su fin en 1980, por boca de quien fuera por diecisiete años primero encargado de la fabricación de vacunas bacterianas y luego director de la institución. Las vicisitudes de la vacuna BCG, la introducción del toxoide tetánico, el fin de la vacuna antivariólica y el triunfo de vacuna antirrábica de Fuenzalida y Palacios, se narran a menudo con comentarios de quienes participaron en estos hechos.

The birth, rise and decline, of vaccine production at the Bacteriological Institute of Chile is recounted by mouth of who was for seventeen years first in charge of manufacturing and then director of the institution. The vicissitudes of the BCG vaccine, the introduction of tetanus toxoid, the end of smallpox vaccine, and the triumph of the rabies vaccine are often related with comments from those who participated in the events.

Infección diseminada por el bacilo vacunal Calmette-Guerin

RESUMEN Introducción: La infección diseminada por el bacilo vacunal Calmette-Guerin es una rara reacción adversa severa asociada a inmunodeficiencia. Objetivo: Describir una serie de cinco casos con infección vacunal diseminada. Presentación de casos: Se presentan cinco casos vacunados al nacer, predominio masculino 4 (80 %), promedio edad inicio: 8,4 meses 2 (15 %) y de edad al diagnóstico: 17,8 meses 6 (31 %). Cuadro clínico de huella vacunal ulcerada, linfadenitis axilar ipsilateral y en regiones distales, hepatosplenomegalia y afectación de otros órganos, con manifestaciones sistémicas y nutricionales. Existió consanguinidad en tres e historia familiar sospechosa de inmunodeficiencia en otros tres. Todos fallecieron: tres enfermos antes de los 3 años. Se realizaron estudios inmunológicos convencionales a todos los enfermos. Un paciente presentaba Inmunodeficiencia severa combinada, en los otros se sospechó enfermedad granulomatosa crónica en uno y síndrome de susceptibilidad mendeliana a micobacterias en tres. Conclusiones: Aunque la vacuna BCG raramente presenta diseminación del bacilo vacunal, debe sospecharse esta entidad en niños pequeños, con las características severas y sistémicas que se describen, con manifestaciones sugestivas de tuberculosis que no responden al tratamiento antituberculoso de primera línea.

ABSTRACT Introduction: The infection disseminated by the vaccine bacillus Calmette-Guerin is a rare severe adverse reaction associated with immunodeficiency. Objective: Describe a series of five cases with disseminated vaccine infection. Presentation of cases : There are five cases vaccinated at birth: predominance of the male sex in 4 (80%), average age onset: 8.4 months in 2 (15 %) and age at diagnosis: 17.8 months in 6 (31 %); clinical picture of ulcerated vaccine footprint, ipsilateral axillary lymphadenitis and in distal regions, hepatosplenomegaly, involvement of other organs, with systemic and nutritional manifestations. There was consanguinity in three of the patients and suspicious family history of immunodeficiency in three others. All died: three were sick before the age of 3. Conventional immunological studies were performed in all cases. One patient had severe combined immunodeficiency, chronic granulomatous disease was suspected in one, and Mendelian susceptibility syndrome to mycobacteria in three. Conclusions: Although the BCG vaccine rarely presents dissemination of the vaccine bacillus, this entity should be suspected in young children, with the severe and systemic characteristics described, with manifestations suggestive to tuberculosis that do not respond to first-line anti-tuberculous treatment.

Role of BCG and Measles vaccination in protection against COVID-19 infection and severity of the disease: A pilot case-control study

Background: The role of BCG and MMR/Measles vaccination in reducing the burden of COVID-19 has been based on ecological data mostly. We planned this explorative pilot case-control study to understand the role of vaccination with Bacillus Calmette朑uerin (BCG) and measles administered as part of MMR vaccine on COVID 19. Methodology: A case-control study was conducted in AIIMS Patna during December 2020 and January 2021. A total of 100 COVID-19 patients confirmed by RT-PCR test were taken as cases, and for each case, age and gender-matched SARS-COV-2 negative individual was taken as control. A study tool containing a pre-tested semi-structured questionnaire was used. Results: The unadjusted odds of COVID-19 were found to be significantly higher among BCG vaccinated [1.88(1.03-4.4)] and MMR vaccinated individuals [5.06(2.34-10.90]. BCG vaccine was not found to have an independent effect on COVID-19 after adjusting for tobacco use, MMR vaccination status, unprotected contact with SARS-COV-2 positive patients, and co-morbidities. But Measles vaccine was found to independently increase the risk of COVID-19 [AOR: 4.505(1.8-11.3)]. Conclusion: BCG vaccination status was not found to be an independent predictor of COVID-19. Further studies with large sample size and better study design (cohort, randomized trials) need to be conducted.

Causes of delayed vaccination of hepatitis B vaccine and BCG in 1 129 children with special health status in Chongqing / 公共卫生与预防医学

Objective To analyze the status of hepatitis B and BCG vaccination in children with special health status, and analyze the reasons for the delay of vaccination, so as to improve the timely vaccination rate. Methods A total of 1 129 children with special health status who were registered and vaccinated in our hospital from September 1, 2018 to January 23, 2020 were selected. All children were classified according to the major diseases based on the discharge records. The first injection time of hepatitis B and BCG vaccine was extracted, and the children were divided into different groups based on the number of people who delayed vaccination. The comparison between groups was performed by χ2 test. Results A total of 87 children without hepatitis B vaccination and 85 children without BCG vaccination were immediately vaccinated in our hospital after the establishment of the archives in our hospital. None of the 1 129 children with special health status had serious adverse reactions after vaccination. The most common diseases in the delayed hepatitis B vaccination children were premature infants, cardiovascular diseases, and nervous system diseases. The most common diseases in the delayed BCG vaccination children were premature infants, cardiovascular diseases, and neonatal disease. There was a significant difference between the number of delayed hepatitis B vaccination and the number of delayed BCG vaccination, with the number of delayed BCG vaccination being more (χ2=278.24, P<0.00). Conclusion Delayed vaccinations are common in children with special health status. Normal vaccination does not increase the incidence of adverse reactions in children with special health status. Medical staff’s understanding of diseases, types of diseases, and types of vaccines are important factors affecting the vaccination of children with special health conditions. Support from social environment, the understanding and cooperation from children's parents and guardians, and the understanding of medical workers on vaccines and diseases are the keys to truly improve the vaccination rate of children..

Clinical efficacy of Bacille Calmette-Guerin polysaccharide nucleic acid combined with montelukast in the treatment of bronchial asthma and its effect on lung function and serum inflammatory factor level / 中国基层医药

Objective:To investigate the clinical efficacy of Bacille Calmette-Guerin polysaccharide nucleic acid combined with montelukast in the treatment of bronchial asthma and its effect on lung function and serum inflammatory factor level.Methods:Eighty patients with bronchial asthma who met inclusion criteria and received treatment in The First People's Hospital of Huzhou from January 2019 to December 2020 were included in this study. They were randomly assigned to undergo either routine systematic treatment and oral montelukast (control group, n = 40) or routine systematic treatment, oral montelukast, and intramuscular injection of Bacille Calmette-Guerin polysaccharide nucleic acid in combination (combined group, n = 40). The changes in serum inflammatory factors and pulmonary function after treatment relative to before treatment, clinical efficacy and adverse reactions were compared between the two groups. Results:Total response rate in the control and combined groups was 80.00% (32/40) and 95.00% (38/40) respectively. Total response rate in the combined group was significantly higher than that in the control group ( χ2 = 4.11, P = 0.043). There were no significant differences in peak expiratory flow rate, forced expiratory volume in 1 second, maximum voluntary ventilation, forced vital capacity, airway resistance and forced expiratory volume in 1 second/forced vital capacity between the two groups before treatment (all P > 0.05). In the combined group, peak expiratory flow rate, forced expiratory volume in 1 second,forced expiratory volume in 1 second/forced vital capacity, maximum voluntary ventilation and forced vital capacity were significantly increased, and airway resistance was significantly decreased after treatment compared with before treatment ( t = -4.81, -5.09, -7.39, -4.12, -7.14, 5.17, all P < 0.001). After treatment, clinical efficacy in the combined group was superior to that in the control group. Before treatment, there were no significant differences in the St George's Respiratory Questionnaire score and Asthma Control Test score between the two groups (both P > 0.05). After treatment, St George's Respiratory Questionnaire score in the combined group was significantly decreased, while Asthma Control Test score was significantly increased compared with before treatment ( t = 9.19, -3.44, both P < 0.001). Before treatment, there were no significant differences in serum interleukin-4, interleukin-5, and interferon-γ levels between the two groups (all P > 0.05). After treatment, serum levels of interleukin-4, interleukin-5, and interferon-γ in the combined group were significantly lower than those in the control group ( t = 6.95, 4.72, -11.24, all P < 0.001). No drugs-related adverse reactions were found in each group during the treatment period. Conclusion:Bacille Calmette-Guerin polysaccharide nucleic acid combined with montelukast is highly effective on bronchial asthma. The combined therapy can improve quality of life and lung function, decrease serum inflammatory factor levels, and is safe.

Relación entre la enfermedad tuberculosa y la vacuna del bacilo de Calmette-Guérin (BCG) en niños

La tuberculosis (TB) es una enfermedad infecciosa, reemergente, ligada a condiciones de pobreza, curable, de presentación clínica variable y con formas graves de enfermedad prevenibles con la vacuna del BCG. Objetivo: Determinar las características de la enfermedad tuberculosa y su asociación con la presencia de la cicatriz de la vacuna (BCG) en los niños que asistieron a la unidad de Tisiología del Ambulatorio docente del HUC. Métodos: Se realizó un estudio de tipo descriptivo, observacional, de corte transversal mediante revisión de las históricas clínicas de todos los niños con el diagnóstico de enfermedad tuberculosa en cualquiera de sus formas clínicas que acudieron al Ambulatorio Docente del HUC durante los años 2014 al 2018, verificando la presencia de la cicatriz de la BCG y su correlación con las formas de la enfermedad. Resultados: Se incluyeron 68 pacientes que cumplieron con los criterios de inclusión y exclusión. El 57 % fue del sexo femenino, el grupo preescolar fue el más frecuente (41 %). La forma clínica predominante fue la pulmonar (63 %), seguida por ganglionar (10 %), meníngea y pleural (5,8 %), la TB miliar (2,9 %). 52 pacientes (76 %) presentaron cicatriz de BCG, siendo en este grupo la forma de presentación clínica más frecuente TB pulmonar (69 %). De los pacientes con ausencia de la cicatriz, el 43,6 % presentó formas graves y extrapulmonares. Conclusiones: La ausencia de cicatriz de BCG, se relacionó con mayoría de formas graves de TB, destacándose la importancia de realizar la vacunación con BCG para la prevención de la enfermedad o de sus formas graves.

Tuberculosis (TB) is an infectious disease, reemerging, linked to conditions of poverty, curable, with variable clinical presentation and with serious forms of disease, preventable through the BCG vaccine. Objective: To determine the characteristics of tuberculosis disease and its association with the presence of the BCG scar in children who attended the consultation of the Tisiology unit of the Teaching Outpatient HUC, in the period January 2014 to December 2018. Methods: A descriptive, observational, cross-sectional study was carried out by reviewing the clinical histories of all children with a diagnosis of tuberculosis disease in any of its clinical forms who attended the HUC Teaching Outpatient Clinic during the period of study, verifying the presence of the BCG scar and its correlation with the different forms of the disease. Results: 68 patients who met the inclusion and exclusion criteria were included. 57 % were female, the most frequent age group was preschool (41 %). The predominant clinical form was pulmonary (63 %), followed by lymph node (10 %), meningeal and pleural (5.8 %), miliary TB (2.9 %). 52 patients (76 %) presented BCG scar, being the most frequent clinical presentation of pulmonary TB (69 %) in this group. Of the patients with absence of the scar, 43.6 % presented severe and extrapulmonary forms. Conclusions: The absence of BCG scar was related to the majority of severe forms of TB, highlighting the importance of BCG vaccination for the prevention of the disease or its serious forms.

Reativação da BCG após vacina contra COVID-19: relato de caso / BCG reactivation after COVID-19 vaccine: case report

A reativação da BCG pode ocorrer em diversos contextos: associada a quadros infecciosos, imunossupressão, autoimunidade e pós-vacinações. Além disso, especialmente em crianças abaixo de 5 anos de idade, deve ser valorizada como um achando presente em cerca de 50% dos casos de Doença de Kawasaki. Neste artigo, relatamos o primeiro caso publicado na literatura de uma paciente adulta jovem, a qual manifestou uma reativação de BCG após receber a primeira dose de vacina contra COVID-19 (AztraZeneca/Oxford/Biomanguinhos). Dentro das primeiras 24h após a administração da vacina, a paciente desenvolveu febre alta, sudorese, dor local, mialgia difusa e cefaleia. Após dois dias, iniciou eritema e enduração no local da cicatriz da vacina BCG. Ela tem como comorbidade a urticária crônica espontânea, porém estava assintomática sem crises há mais de 1 ano. Tem como antecedente familiar relevante o óbito materno por síndrome complexa de sobreposição de autoimunidade (lúpus eritematoso sistêmico, síndrome de Sjögren e síndrome do anticorpo antifosfolípide). Após ser medicada com anti-inflamatórios não esteroides (AINE) e corticoterapia tópica de moderada potência por 3 dias, houve resolução completa da reativação da BCG. A paciente, após 3 meses, recebeu a segunda dose da vacina e não manifestou nenhum sintoma. Acredita-se que a reativação da BCG ocorra devido a um mecanismo de reação cruzada entre HSP do indivíduo, elicitadas como mediadores da imunidade inata frente à inflamação vacinal, com alguns epítopos do M. bovis. Recomendase que seja investigada alguma condição imunossupressora ou autoimune nos pacientes que manifestem reativação da BCG, principalmente em adultos, na qual a doença de Kawasaki é bastante rara. As vacinas, incluindo as contra COVID-19, também podem desencadear o surgimento deste fenômeno imunológico ainda pouco compreendido.

BCG reactivation can occur in different contexts: associated with infectious conditions, immunosuppression, autoimmunity and post-vaccinations. Also, especially in children below of 5 years of age, should be valued as a finding present in about 50% of cases of Kawasaki disease. In this article, we report the first case published in the literature of a young adult patient, who manifested a reactivation of BCG after receiving the first dose of vaccine against COVID-19 (AztraZeneca/Oxford/Biomanguinhos). Within the first 24 hours after the administration of the vaccine, the patient developed high fever, sweating, local pain, diffuse myalgia and headache. After 2 days, erythema and induration at the site of the BCG vaccine scar began. she has how comorbidity to chronic spontaneous urticaria, but she was asymptomatic without crises for more than 1 year. The relevant family history is maternal death due to the complex syndrome of autoimmunity overlap (systemic lupus erythematosus, Sjögrens syndrome, and anti-phospholipid antibody). After being medicated with NSAID and moderate topical corticosteroid therapy potency for 3 days, there was complete resolution of BCG reactivation. The patient, after 3 months, received the 2nd dose of the vaccine and had no symptoms. It is believed that the reactivation of BCG occurs due to a cross-reaction mechanism between the individuals HSP, elicited as mediators of innate immunity against vaccine inflammation, with some epitopes of M. bovis. It is recommended that any immunosuppressive or autoimmune condition be investigated in patients that manifest BCG reactivation, especially in adults, in which Kawasaki disease is quite rare. Vaccines, including those against COVID-19, can also trigger of this immunological phenomenon still poorly understood.

Estratégia de vacinação da BCG: unidade de saúde versus maternidade / BCG vaccination strategy: health unit versus maternity

Objetivo: comparar a estratégia atual de vacinação BCG em Unidade de Saúde com a alternativa de aplicação em maternidades/hospitais no município de Porto Alegre - Rio Grande do Sul. Metodologia: trata-se de um estudo de abordagem quantitativa, com base em dados de espelhos dos registros físicos das carteiras de vacinação e dados secundários de sistemas de informação de saúde, relativos ao período 2010 a 2014. Resultados: apenas 3,7% dos nascidos vivos foram vacinados nas primeiras 12 horas de vida, enquanto 50,1% o foram na primeira semana e 22,9% após os 15 dias de vida, aumentando o risco de exposição à tuberculose. Somente 22% das doses distribuídas às unidades de saúde foram aplicadas indicando elevado desperdício de doses e recursos financeiros. Conclusão: a estratégia de aplicação da BCG em Unidade de Saúde não corresponde à melhor alternativa de vacinação para o município sugerindo-se, portanto, a aplicação ainda na maternidade/hospital de nascimento.

Objective: To compare the current BCG vaccination strategy in Health Units with the alternative of application in maternity/hospitals in the city of Porto Alegre - Rio Grande do Sul. Methodology: This is a quantitative study based on mirror data from physical records of vaccination cards and secondary data from health information systems from 2010 to 2014. Results: Only 3.7% of live births were vaccinated in the first 12 hours of life, while 50.1% were in the first week, and 22.9% after 15 days of life, increasing the risk of exposure to tuberculosis. Only 22% of the doses distributed to the health units were applied, indicating high waste of doses and financial resources. Conclusion: The strategy of BCG application in Health Units does not correspond to the best vaccination alternative for the city, suggesting, therefore, the application still in the maternity/hospital of birth.