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.

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.

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.

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.

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.

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.

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.

The diagnostic value of PSA and multi-parameter MRI in granulomatous prostatitis after intravesical Bacillus Calmette-Guérin therapy / 中华泌尿外科杂志

Objective:To evaluate the diagnostic value of serum prostate-specific antigen (PSA) levels and multi-parameter magnetic resonance imaging (mpMRI) in patients with granulomatous prostatitis after intravesical Bacillus Calmette-Guérin (BCG) therapy.Methods:The medical records of eight patients with pathologically proven granulomatous prostatitis in Shandong Provincial Hospital Affiliated to Shandong University from January, 2015 to June, 2020, were enrolled and analyzed in this retrospective study. All 8 patients (ages 47-76, mean 63.6) underwent pelvic mpMRI and serum tPSA levels before TURBT, which showed the results of tPSA, f/t and mpMRI were normal before TURBT (0.45-3.62 ng/ml, 0.20-0.51 and normal signal intensities on T1WI and T2WI, respectively). All patients underwent intravesical BCG therapy after post-TURBT 4-6-weeks’ intravesical gemcitabine therapy as a result of pathologically proven middle and high risk NMIBC via cystoscopy.Results:The results of tPSA levels in all 8 patients were elevated after intravesical BCG therapy after 9-15 months (mean 10.5 months), with 4 patients above 4 (6.77-12.89)ng/ml and 4 patients within the normal ranges(2.02-2.68)ng/ml, and f/t levels decreased to lower than 0.16 (0.09-0.15)in all patients. The mpMRI abnormal signals in all patients were all located in the peripheral zone of prostate. All nodular lesions of prostate mpMRI showed lower signal intensity (SI) on T2WI, higher SI on DWI and lower SI on ADC after BCG therapy. All patients underwent prostate biopsy for abnormal signal on prostate mpMRI. The biopsy pathologic results of all patients were granulomatous prostatitis.Conclusions:When elevated PSA and abnormal signals on prostate mpMRI after intravesical BCG therapy occurred, prostate biopsy may not be required for secondary granulomatous prostatitis patients with non-muscle invasive bladder cancer in combination of clinical history.

Vacuna BCG e indicadores de mortalidad y morbilidad por COVID-19 en países con curva epidémica consolidada / TB vaccine and indicators of mortality and morbidity from COVID-19 in countries with a consolidated epidemic curve / Vacina BCG e indicadores de mortalidade e morbidade por COVID-19 em países com curva epidêmica consolidada / Vaccin BCG et indicateurs de mortalité et de morbidité dus au COVID-19 dans les pays à courbe épidémique consolidée

Resumen Objetivo: Señalar posible influencia de coberturas de vacunación con bacilos Calmette-Guérin (BCG) en indicadores de mortalidad y morbilidad por COVID-19, en países con curva epidémica consolidada. Materiales y Métodos: Se trata de un estudio ecológico mixto, del total de países que integran la Organización Mundial de la Salud (OMS).Se eligieron aquellos con curva epidémica consolidada por COVID-19, actualizada al 1 de junio 2020 e información tomada de base de datos de vacunación 1980-2018 Estimates of National Immunization Coverage, ambas fuentes de OMS, contrastando las coberturas y políticas de vacunación universal e ingreso per cápita con letalidad, mortalidad e incidencia en 45 países que cumplieron con los criterios, aplicando medidas de asociación e impacto potencial: riesgo relativo(RR) reducción de riesgo(RDR), muertes prevenibles en vacunados(MEV%), casos prevenibles en vacunados(CEV%) con intervalo de confianza para tasas con 99% de significancia. Resultados: Países con coberturas mayor de 60% y política actual de vacunación universal, en contraste con países con cero% coberturas, con reducción de indicadores de mortalidad y morbilidad: Letalidad 5.8-9.7%, mortalidad 883.8-937 por 106 (p<0.01) habitantes, incidencia 4,260-4,351.6 por 105 (p<0.01) habitantes; incremento de: MEV% 94.1-99.8%(p<0.01) y CEV% 96.9-99.6%(p<0.01). El mayor contraste de indicadores fue para países con ingreso medio bajo e ingreso medio alto. Países con coberturas menor de 60% contra cero % coberturas (ambos grupos con altos ingresos) con reducción (excepto Letalidad): Letalidad-1.861 a -4.703 %(p>0.01), mortalidad 774.3- 827.8 por 106 (p<0.01) habitantes, incidencia 4,193.13- 4,212.93 por 105 (p<0.01) habitantes, incremento de: MEV% 82.5-88.2%(p<0.01), CEV% 96.0-96.5%(p<0.01). También mayor diferencia de indicadores para países con coberturas cercanas al 60%, con política de vacunación universal actual. Conclusiones: Los países con coberturas de vacunación con BCG superior a 60% con mantenimiento de políticas de vacunación universal, tienen mayor reducción de indicadores de mortalidad, morbilidad por COVID-19 e incremento significativo de casos y muertes evitadas sugiriendo posible influencia por vacunación entre otros factores.

Abstract Objective: Indicate the possible influence of vaccination coverage with Calmette-Guérin bacilli (BCG) on indicators of mortality andmorbidity from COVID-19 in countries with a consolidated epidemic curve. of association and potential impact: relative risk (RR) Materials and methods: This is a mixed ecological study of all the countries that make up the World Health Organization (WHO). Those with an epidemic curve consolidated by COVID-19 updated to June 1, 2020 and information taken from the vaccination database 1980-2018 Estimates of National Immunization Coverage, both sources of WHO, were chosen, contrasting the coverage and policies of universal vaccination and income per capita with lethality, mortality and incidence in 45 countries that met the criteria applying measures of association and potential impact: relative risk (RR), risk reduction (RDR), preventable deaths in vaccinated (MEV%), preventable cases in vaccinated (CEV%) with confidence interval for rates with 99% significance. Results: Countries with coverage greater than 60% and current universal vaccination policy in contrast to countries with zero% coverage, with reduction in mortality and morbidity indicators: Mortality 5.8-9.7%, mortality 883.8-937 per 106 (p <0.01) inhabitants, incidence 4,260-4,351.6 per 105 (p <0.01) inhabitants; Increase of: MEV% 94.1-99.8% (p <0.01) and CEV% 96.9-99.6% (p <0.01). The greatest contrast of indicators were for countries with lower middle income and upper middle income. Countries with coverage less than 60% versus zero% coverage (both groups with high incomes) with reduction (except case fatality): case fatality-1.861 to -4.703% (p> 0.01), mortality774.3-827.8 per 106 (p <0.01) inhabitants, incidence 4,193.13- 4,212.93 per 105 (p <0.01) inhabitants, increase of: MEV% 82.5- 88.2% (p <0.01), CEV% 96.0-96.5 (p <0.01) .Also greater difference of indicators for countries with coverage close to 60% with current universal vaccination policy. Conclusions: Countries with BCG vaccination coverage greater than 60% with maintenance of universal vaccination policies, have a greater reduction in mortality indicators, morbidity from COVID-19 and a significant increase in cases and deaths, suggesting possible influence by vaccination among other factors.

Resumo Objetivo: Indique a possível influência da cobertura vacinal com bacilos de Calmette-Guérin (BCG) nos indicadores de mortalidade e morbidade do COVID-19 em países com uma curva epidêmica consolidada. Materiais e métodos: É um estudo ecológico misto do número total de países que compõem a Organização Mundial da Saúde (OMS). Aqueles com uma curva epidêmica consolidada pelo COVID-19 atualizada para 1º de junho de 2020 e informações retiradas do banco de dados de vacinação 1980-2018, foram escolhidas as Estimativas de Cobertura Nacional de Imunizações, ambas as fontes da OMS, contrastando a cobertura e as políticas de vacinação universal e renda. per capita com letalidade, mortalidade e incidência em 45 países que atenderam aos critérios de aplicação de possíveis medidas de associação e impacto: risco relativo(RR),redução de risco (RDR), mortes evitáveis em vacinados (MEV%), casos evitáveis em vacinados (CEV%) com intervalo de confiança para taxas com significância de 99%. Resultados: Países com cobertura superior a 60% e política atual de vacinação universal em contraste com países com cobertura zero, com redução nos indicadores de mortalidade e morbidade: Mortalidade 5,8-9,7%, mortalidade 883.8-937 por 106 (p <0,01) habitantes, incidência 4,260-4,351.6 por 105 (p <0,01) habitantes; Aumento de: MEV% 94.1-99.8% (p <0,01) e CEV% 96.9-99.6% (p <0,01). O maior contraste de indicadores ocorreu nos países com renda média baixa e renda média alta. Países com cobertura inferior a 60% versus zero% (ambos os grupos com renda alta) com redução (exceto casos fatais): casos fatalidade -1.861 a -4.703 % (p> 0,01), mortalidade 774.3-827.8 por 106 habitantes (p <0,01), incidência 4,193.13- 4,212.93 por 105 (p <0,01) habitantes, aumento de: MEV% 82.5-88.2 % (p<0,01), CEV% 96.0-96.5% (p <0,01). Também maior diferença de indicadores para países com cobertura perto de 60% com a atual política universal de vacinação. Conclusões: Os países com cobertura vacinal para BCG superior a 60% com manutenção de políticas universais de vacinação apresentam maior redução nos indicadores de mortalidade, morbidade por COVID-19 e um aumento significativo de casos e mortes evitaram sugerir uma possível influência através da vacinação, entre outros fatores.

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Inmunodeficiencia Combinada Severa, reporte de pacientes chilenos diagnosticados durante el período 1999-2020

Introducción: La inmunodeficiencia combinada severa (IDCS) corresponde a una de las formas más graves de inmunodeficiencia primaria, existiendo escasos datos nacionales sobre ésta. Objetivo: describir la epidemiología, complicaciones, pronóstico y uso de la vacuna BCG en pacientes chilenos con IDCS. Pacientes y Método: Estudio retrospectivo de pacientes diagnosticados con IDCS entre los años 1999 y 2020 por médicos inmunólogos a lo largo de Chile. El diagnóstico de IDCS se realizó conforme a los criterios propuestos por Shearer: linfocitos T (CD3+) < 300 células/μL y prolife ración 10% del límite de normalidad en respuesta a fitohemaglutinina o presencia de linfocitos T de origen materno. Se obtuvieron de la ficha clínica los datos correspondientes a: sexo, edad al diagnóstico, consanguinidad, región de origen, subpoblaciones linfocitarias, diagnóstico genético, complicaciones infecciosas y no infecciosas, vacunación BCG y sus complicaciones, edad de deriva ción al centro de TPH y causa de mortalidad no relacionada al TPH. Resultados: se diagnosticaron 25 casos de IDCS en 22 familias entre los años 1999-2020. 78% varones, la edad media a la primera manifestación fue 2.3 meses (0-7), mientras que la edad media al diagnóstico fue de 3.4 meses (0 7). Un 16% de los casos tenía un antecedente familiar de IDCS. Un 40% de los casos fueron diag nosticados en la Región Metropolitana. El inmunofenotipo más frecuente fue T-B-NK+ (48%). Se realizaron estudios genéticos en 69,5% de los casos, siendo los defectos genéticos en RAG2 (39%) la causa más frecuente. Un 88% de los casos recibió la vacuna Bacillus Calmette-Guerin (BCG) previo al diagnóstico, incluidos 2 pacientes con historia familiar positiva, 36% de los vacunados experimentó complicaciones de la BCG. La edad media a la derivación a trasplante fue de 7,4 meses (5-16). De los 25 pacientes, 11 fallecieron previo a la derivación a un centro de trasplante. Conclu sión: En Chile existe un retraso clínicamente significativo entre las primeras manifestaciones y el diagnóstico de IDCS, así como un importante retraso en la derivación a centros de trasplante. La mayoría de los pacientes con IDCS reciben la vacuna BCG, pese a tener antecedentes familiares, y experimentan frecuentemente complicaciones de la vacuna.

Introduction: Severe combined immunodeficiency (SCID) is the most severe form of primary immunodeficiency. To date, there is little local information about this disease. Objective: To describe the epidemiology, complications, prognosis, and use of the BCG vaccine in Chilean patients with SCID. Patients and Method: Retrospective review of the clinical records of patients diagnosed with SCID by clinical immunologists between 1999 and 2020 throughout Chile. SCID was diagnosed according to the cri teria proposed by Shearer: T lymphocytes (CD3+) < 300 cells/μL and proliferation 10% of the limit of normality in response to phytohemagglutinin or presence of T lymphocytes of maternal origin. Data collected from the clinical records were: sex, age at diagnosis, consanguinity, region of origin, lymphocyte subpopulations, genetic diagnosis, infectious and non-infectious complications, BCG vaccination and its complications, age at referral to the bone marrow transplant (BMT) center, and cause of non-BMT-related mortality. Results: Between 1999 and 2020, 25 patients were diagnosed with SCID. 78% of them were male, mean age at first manifestation of the disease was 2.3 months (0-7), while the mean age at diagnosis was 3.4 months (0-7). 16% of patients had a family history of SCID. 40% of cases were diagnosed within the Metropolitan Region. The most frequent immuno- phenotype was T-B-NK+ SCID (48%). Genetic studies were done in 69.5% of cases, mutations in the RAG2 gene were the most common etiology of SCID (39%). 88% of SCID patients received the Bacillus Calmette-Guerin (BCG) vaccine before diagnosis, including 2 cases with a known family history of SCID. 36% of those who received the vaccine had BCG-related complications. The mean age at referral to a bone marrow transplant center was 7.4 months (5-16). 11/25 patients died before being transferred to a transplant center. Discussion: There is a clinically significant delay between the first manifestations and the diagnosis of SCID in Chilean patients, as well as an important time gap between the diagnosis of SCID and referral to a center for BMT. Most SCID cases in Chile receive the BCG vaccine, despite a known family history of the disease, and frequently develop vaccine-related complications.

Bladder Cancer at the time of COVID-19 Outbreak

ABSTRACT The COVID-19 outbreak has led to the deferral of a great number of surgeries in an attempt to reduce transmission of infection, free up hospital beds, intensive care and anaesthetists, and limit aerosol-generating procedures. Guidelines and suggestions have been provided to categorize Urological diseases into risk groups and recommendations are available on procedures that can be or cannot be deferred. We aim to summarise updates on diagnosis, treatment and follow up of bladder cancer during the COVID-19 outbreaks.

Importance of epidemiological surveillance of leprosy: analysis of the occurrence of leprosy in intra-domiciliary contacts in a capital in the Brazilian northeast region

Abstract INTRODUCTION Intra-domiciliary contacts are a group with the highest risk of developing leprosy. METHODS A cross-sectional study of intra-domiciliary contacts of new leprosy cases was conducted. A descriptive analysis of the variables was performed. RESULTS Among 190 contacts, 63% were invited to visit the health unit, and 54.2% received the BCG vaccine. The prevalence of leprosy among the contacts was 4.7%. CONCLUSIONS The occurrence of leprosy among the contacts was high and similar to that found previously. There were failures in surveillance actions carried out by health units. Never-before treated cases were found.

Vacunación BCG e inmunodeficiencias primarias: ¿es momento de un cambio? / BCG vaccine administration schedule and primary immunodeficiencies: Is it time for a change?

Resumen: Los pacientes con Inmunodeficiencias primarias (IDP) tienen un riesgo elevado de complicaciones severas por la vacuna BCG, incluso mortalidad. Es necesario evaluar periódicamente el riesgo versus beneficio de la vacunación universal BCG en el periodo neonatal. Chile es un país con baja incidencia de tuberculosis (TB) pero cuya epidemiología ha cambiado recientemente con un aumento de los casos. Cambios en esquemas de vacunación BCG en países con incidencias mayores o similares de TB y con coberturas de vacunación menores han sido posibles sin aumento de los casos graves de TB que son los que previene la BCG. El cambio ha evitado complicaciones graves en pacientes con IDP. Creemos que un análisis crítico de la fecha de vacunación BCG debe realizarse hoy en Chile. Más aún dada la posibilidad técnica de realizar screening neonatal de IDP.

Abstract: Patients with Primary Immunodeficiencies (PID) are at a higher risk of developing severe morbidities and mortality due to the administration of BCG vaccine. Risk-to-benefit of universal BCG vaccina tion of newborns must be assessed periodically. Chile has a low incidence of tuberculosis (TB) but the local epidemiology has recently changed with an increase of TB cases. Changes in the BCG vaccine schedule have been made in countries with similar or higher TB incidences and lower BCG vaccine coverage, with no increase in the severe TB cases, which are prevented by BCG. These changes have prevented serious complications in PID patients. We propose a critical analysis of the BCG adminis tration date in Chile due to the technical possibility of performing neonatal PID screening.

Cross Sectional Comparative Study Of Awareness Of Bcg Vaccine And Tuberculosis Among Urban And Rural Population

The cross sectional comparative study was aimed at assessing the awareness BCG Vaccine and Spread of tuberculosis among Urban and Rural Population. AIM:-1. To Study the awareness of BCG Vaccine among urban and rural study population and compare between urban and rural study population. 2. To study the knowledge of spread of tuberculosis and compare among Urban and Rural Population. 200 odd patients from Urban and Rural area were included. 87 participants out of 200 were of the opinion that BCG gives complete protection. Out of which, 74.72%participants were from urban and 25.28% were from rural area. 79 participants were in the opinion of partial protection. Out of which, 62.02% (49) were rural participants and 37.98% (30) were urban participants. Regarding knowledge of tuberculosis, misconception was seen more or less in both the population. It is a need of time to increase awareness of knowledge of tuberculosis.

Infección diseminada por Bacilo Calmette-Guérin en un lactante con inmunodeficiencia: reporte de caso / Disseminated infection by Bacillus Calmette-Guérin in an immunodeficient infant: case report

RESUMEN La vacuna Bacillus Calmette-Guerin (BCG) que se administra a los recién nacidos de países con alta incidencia de tuberculosis puede ocasionar reacciones locales hasta infección diseminada en pacientes inmunocomprometidos. Reportamos el caso de un lactante varón de seis meses con antecedente de haber recibido vacuna BCG al nacer, y presentar cuadros infecciosos a repetición, nódulos violáceos blandos en tronco y extremidades con presencia de bacilos ácido alcohol resistentes (BARR) en la histopatología y en cultivo de piel; el estudio molecular reportó la presencia de Micobacterium bovis BCG. En la tomografía se observó opacidades intersticiales en pulmones y en el lavado gástrico se identificó BAAR. El estudio genético del paciente y de la madre reveló la presencia de mutación en el gen IL2RG confirmando el diagnóstico de inmunodeficiencia combinada severa, recibe tratamiento con inmunoglubolina humana y esquema antituberculosis con isoniacida, rifampicina y etambutol. Presentamos el caso por la implicancia en el pronóstico de vida de estos pacientes y por la necesidad de un diagnóstico preciso y oportuno.

ABSTRACT The Bacillus Calmette-Guerin (BCG) vaccine given to newborns in countries with a high incidence of tuberculosis may cause local reactions up to disseminated infection in immunocompromised patients. We report the case of a six-monthold male infant with a history of having received the BCG vaccine at birth, and presenting repeated infectious, soft violet nodules in the trunk and extremities with the presence of acid-alcohol-resistant bacilli (BAAR) in histopathology and skin culture; the molecular study reported the presence of Mycobacterium bovis BCG. In the tomography, interstitial opacities were observed in the lungs and in the gastric lavage BAAR was identified. The genetic study of the patient and the mother revealed the presence of a mutation in the IL2RG gene confirming the diagnosis of severe combined immunodeficiency. Received treatment with human immunoglobulin and anti-tuberculosis scheme with isoniazid, rifampicin, and ethambutol. We present the case because of the implication in the life prognosis of these patients and because of the need for an accurate and timely diagnosis

PPD results after 3-6 years of BCG vaccination and its effect on latent tuberculosis infection in children / 中国学校卫生

Objective@#To understand the results of tuberculin skin test (PPD) in preschool children after the vaccination of BCG, and to analyze the effect of BCG vaccination on latent tuberculosis infection in children.@*Methods@#From January to November 2018, a total of 1 359 preschool children from 14 kindergartens in 8 districts and cities of Jiangsu Province were selected for tuberculin test(PPD), and chest X-ray examination was performed on children with strong PPD results.@*Results@#The positive rate of PPD in preschool children in Jiangsu Province was 23.33%, of which strong positive and moderate positive (PPD≥10 mm) were totaled 6.47%. There were 149 boys (21.29%) with PPD positive reactions and 168 girls(25.50%) with PPD positive reactions, and differences of PPD positive reactions with different genders were of no statistical significance (χ2=3.36, P>0.05) And there were 201 children (25.35%) with PPD positive reactions in northern Jiangsu, 116 children (20.50%) with PPD positive reactions in southern Jiangsu. There were significant differences in the results of PPD positive and negative reactions between different regions(χ2=4.35, P<0.05). There was 1 case of PPD positive reactions among 3-year-old children(0.71%), 19 cases among 4-year-old children(3.89%), 31 cases among 5-year-old children(8.96%), and 37 cases among 6-year-old children(9.63%), and the differences of PPD positive reactions of different age groups were of statistical significance(χ2=21.69, P<0.01).@*Conclusion@#The positive rate of PPD in preschool children in Jiangsu Province is very low, indicating that PPD can be used as a detection method for latent infection in children. The overall positive rate of PPD in preschool children in Jiangsu Province is also low, and appropriate measures should be taken to protect susceptible children and effectively prevent and control childhood tuberculosis.

Evaluation of EZplex MTBC/NTM Real-Time PCR kit: diagnostic accuracy and efficacy in vaccination

PURPOSE: Tuberculosis (TB) is mainly caused by Mycobacterium tuberculosis, which is a pathogenic mycobacterial species grouped under Mycobacterium tuberculosis complex (MTBC) with four other pathogenic mycobacterial species. The mycobacteria not included in MTBC are known as nontuberculous mycobacteria (NTM), and cause several pulmonary diseases including pneumonia. Currently, NTM occurrences in TB-suspected respiratory specimens have increased, due to which, precise detection of MTBC and NTM is considered critical for the diagnosis and vaccination of TB. Among the various methods available, real-time PCR is frequently adopted for MTBC/NTM detection due to its rapidness, accuracy, and ease of handling. In this study, we evaluated a new real-time PCR kit for analytical and clinical performance on sputum, bronchial washing, and culture specimens. MATERIALS AND METHODS: For assessing its analytical performance, limit of detection (LOD), reactivity, and repeatability test were performed using DNA samples. To evaluate clinical performance, 612 samples were collected and clinically tested at a tertiary hospital. RESULTS: LOD was confirmed as 0.584 copies/µL for MTBC and 47.836 copies/µL for NTM by probit analysis (95% positive). For the reactivity test, all intended strains were detected and, in the repeatability test, stable and steady results were confirmed with coefficient of variation ranging from 0.36 to 1.59. For the clinical test, sensitivity and specificity were 98.6%–100% and 98.8%–100% for MTBC and NTM, respectively. CONCLUSION: The results proved the usefulness of the kit in TB diagnosis. Furthermore, it could be adopted for the assessment of vaccine efficacy.

Expression of miRNA-29a in U937 macrophages infected with Mycobacterium tuberculosis and its regulation of target genes / 中华临床感染病杂志

Objective To analyze the expression of miRNA-29a in U937 macrophages infected with Mycobacterium tuberculosis and its regulation of target genes.Methods The target genes of miRNA-29a were predicted with softwares miRnada,RNAhybrid and targetscan.The differentiation of U937 macrophages was induced by phorbol ester(PMA), the induced U937 cells were infected with bacilli calmette guerin (BCG).The expression levels of miRNA-29a and its target genes in U937 cells were detected with real-time fluorescence quantitative PCR(RT-fqPCR).The miRNA-29a over-and low-expression U937 macrophage cell lines were constructed and the levels of miRNA-29a and its garget genes were detected.The SPSS 18.0 software was used to analyze the data.Results As predicted by relevant softwares,the miRNA-29a regulate the expression of VEGFA,NFATC3 and TSC22D3 genes.After BCG infection,the expression of miRNA-29a increased to 1.33 fold(P <0.05), and the expression levels of VEGFA, NFATC3 and TSC22D3 were increased to 5.34,99.25 and 2.12 fold,respectively(P<0.01).In the miRNA-29a over-expressing U937 macrophages,the expression levels of VEGFA,NFATC3 and TSC22D3 were up-regulated to 1.35,1.29 and 3.38 fold,respectively(P<0.05 or <0.01).While in the U937 macrophages with miRNA-29a knock-down,the expression levels of VEGFA, NFATC3 and TSC22D3 were down-regulated to 0.07, 0.08 and 0.55 fold, respectively(P <0.01).Conclusion The results suggest that Mycobacterium tuberculosis infection can increase the expression of miRNA-29a in U937 macrophages,further targeting the regulation of VEGFA, NFATC3 and TSC22D3 gene expression, which may participate in the pathogenesis and development of tuberculosis.

Bacillus Calmette-Guerin vaccine promotes human dendritic cell miRNA-99b to regulate CD4 +initial T cells differentiation to Th17/Treg imbalance / 中华临床感染病杂志

Objective To investigate the effects of human dendritic cells ( DCs) infected by bovine Mycobacterium tuberculosis attenuated live bacteria ( BCG) on differentiation of CD4 +naive T cells from neonate cord blood .Methods After infected with BCG , human DCs were cultured with CD 4 +naive T cells from neonate cord blood, the expression of miRNA-99b in DCs and the expression of Foxp3, ROR-γt, IFN-γand IL-10 mRNAs in CD4+ T cells were detected by qRT-PCR.DCs were transfected with miRNA-99b antisense oligonucleotides and co-cultured with neonatal cord blood CD 4 +naive T cells , and the transcription level of CD4 +T cell-related genes was detected .SPSS 15.0 was used to analyze the data .Results The transcriptional activity of miRNA-99b gene in BCG-infected DCs was significantly higher than that in uninfected DCs (t=7.06,P<0.01).Compared with CD4 +T cells co-cultured with uninfected DCs, the mRNA expression of IFN-γ(45.61 ±4.46 vs.3.54 ±1.73, t=32.32, P<0.01), IL-10 (4.17 ±1.06 vs.1.26 ±0.67, t=2.24, P<0.05) in CD4 +T cells co-cultured with BCG-infected DCs was significantly increased, while the mRNA expression of ROR-γt was significantly decreased ( 0.08 ±0.02 vs.0.63 ± 0.10, t=0.42, P<0.01).Compared with CD4 +T cells co-cultured with DCs transfected with NC-siRNA, the miRNA-99b expression was blocked , the mRNA expression of Foxp3 (0.12 ±0.01 vs.1.57 ±0.90, t=1.06, P<0.05), IFN-γ(0.03 ±0.01 vs.0.64 ±0.35, t =0.44, P<0.05), IL-10(0.03 ±0.01 vs. 0.76 ±0.09, t=0.54,P<0.01) in CD4 +T cells was significantly decreased , while the expression ROR-γt mRNA was significantly increased (17.03 ±5.51 vs.1.32 ±0.14, t=11.54,P<0.01).Conclusion BCG induces the imbalance of initial CD 4 +T lymphocytes into Th17/Treg by regulating the expression of miRNA-99b in DCs, leading to the occurrence and development of infection .