Effectiveness of Bacille Calmette-Guerin Vaccination Policies in reducing infection and severity of COVID-19: A systematic review protocol

@#<p style="text-align: justify;"><strong>Introduction:</strong> The bacille Calmette-Guerin (BCG) vaccine is used for the prevention of tuberculosis (TB) worldwide. Evidence reports a much lower incidence of COVID-19 in TB-endemic areas implying a possible protective mechanism of BCG in countries with mandated BCG policies. The objective of the study is to synthesize and critically evaluate the effectiveness of national BCG vaccination policies in reducing infection and severity of COVID-19 in their native population.</p><p style="text-align: justify;"><strong>Methods:</strong> Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a comprehensive search using pre-identified keywords will be done in PubMed, Cochrane, HERDIN Plus, WPRIM, Web of Science and EBSCO databases. After the initial selection of studies based on eligibility criteria, methodological appraisal will be conducted using the Joanna Briggs Institute appraisal instruments and an adapted quality assessment checklist for ecologic studies. Relevant data will be extracted and synthesized including reporting descriptive and inferential statistics to interpret results.</p><p style="text-align: justify;"><strong>Results:</strong> The study will generate a systematic review synthesizing evidence regarding the effects of BCG in curtailing the spread of the COVID-19 pandemic.</p><p style="text-align: justify;"><strong>Discussion:</strong> The battle against the COVID-19 pandemic is far from over, and as such, further studies must be undertaken to verify the evidence behind initial strategies in battling it. This includes the use of BCG in decreasing COVID-19 incidence and mortality. The results of the review can ultimately guide health authorities and policy makers create evidence-based decisions regarding BCG vaccination policies and clinical trials related to COVID-19 control and prevention.</p><p style="text-align: justify;"><strong>Systematic Review Registration:</strong> PROSPERO, CRD42021244060</p>

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.

Infección por Mycobacterium bovis en una adolescente con síndrome febril prolongado / Mycobacterium bovis infection in an adolescent with prolonged febrile syndrome

La tuberculosis bovina es una zoonosis causada por Mycobacterium bovis. El bovino es el huésped primario. Otras especies pueden ser infectadas (cerdos, cabras y caballos, entre otras). En el ser humano, el contagio puede ser por vía aérea (enfermedad pulmonar), clínicamente indistinguible de la producida por Mycobacterium tuberculosis, o por vía oral o cutánea, (formas extrapulmonares: digestiva, ganglionar, cutánea). Su contagio se ha relacionado principalmente al contacto con el ganado y al consumo de lácteos sin pasteurizar. También se notificó el posible contagio interpersonal.Se describe el caso de una paciente adolescente, proveniente de la provincia de Buenos Aires, con síndrome febril prolongado y conglomerado ganglionar abdominal, con antecedente de ingestión de leche no pasteurizada. Es fundamental alertar acerca de la importancia del procesamiento correcto de los alimentos, sobre todo en esta época en la que las nuevas tendencias alimentarias (ingestión de lácteos caseros o comprados en ferias informales) pueden poner en riesgo la salud.

Bovine tuberculosis is an infectious, zoonotic disease, caused by Mycobacterium bovis. The bovine is the primary host. Other species can be infected (pigs, goats, horses, etc). Man can be infected by air (lung disease), clinically indistinguishable from that produced by Mycobacterium tuberculosis or by oral or cutaneous route (extrapulmonary forms: digestive, lymph node, skin). Contagion has been mainly related to contact with livestock and the consumption of unpasteurized dairy products. It was also reported the possible contagion between people. It is described the case of an adolescent patient, from the province of Buenos Aires, with prolonged febrile syndrome and abdominal lymph node conglomerate, with a history of ingestion of unpasteurized milk. We consider the importance of warning about the correct processing of food, especially at this time when new food trends (homemade dairy intake or bought at informal fairs) could put the health of the population at risk.

Spatial and temporal analyses of culls due to bovine tuberculosis in slaughterhouses of Minas Gerais state, Brazil, 2008 to 2012 / Análise espacial e temporal das condenações por tuberculose bovina em frigoríficos do estado de Minas Gerais, Brasil, 2008 a 2012

The application of spatial and temporal analysis in epidemiology aims to understand the causes and consequences of spatial and temporal heterogeneity in studies of infectious diseases. Bovine tuberculosis (bTB) is a chronic and progressive infectious disease caused by Mycobacterium bovis and is an important zoonosis worldwide. The aim of this study was to conduct spatial and temporal analyses of a secondary database of bTB-positive cases registered by the Federal Inspection Service in two slaughterhouses from the West of Minas mesoregion of Minas Gerais state, Brazil, from 2008 to 2012 and to suggest its use in epidemiological surveillance. The culled cattle with bTB macroscopic lesions during post mortem inspection were considered positive in this study. The data used were the positive cases registered on the "Sistema de Informações Gerenciais do Serviço de Inspeção Federal" (SIG/SIF - Management Information System of the Federal Inspection Service) of the "Ministério da Agricultura, Pecuária e Abastecimento" (MAPA - Ministry of Agriculture, Livestock and Supplies), the number of animals slaughtered monthly and their municipalities of origin, per slaughterhouse. The prevalence (%) of cases per cattle slaughtered was calculated, and the relationship between these cases of bTB and cases of human tuberculosis (hTB) and the GDP per capita of the mesoregions comprising the municipalities surveyed was evaluated. The prevalence was 1,030 cases of bTB (0.28%). The lowest case numbers and prevalence rates were obtained in 2010, while the highest rates were observed in 2011. Slaughterhouse 1 showed stationarity, while Slaughterhouse 2 showed an increasing annual trend for data since October 2009. A statistical correlation between the numbers of cases of bovine and human TB (p=0.006, r=0.148) was observed. The prevalence for Slaughterhouses 1 and 2 were not correlated (p>0.05). The municipalities of origin demonstrated randomness in their spatial distribution. SIG/SIF-MAPA may be used for the analysis of spatial and temporal distribution to contribute to the monitoring of animal health services with information on the prevalence of culling for bTB in the West of Minas, South/Southwest of Minas, Campo das Vertentes and Zona da Mata mesoregions of Minas Gerais, Brazil.(AU)

A aplicação de análises espacial e temporal em epidemiologia visa compreender as causas e consequências da heterogeneidade espacial e temporal nos estudos de doenças infecciosas. A tuberculose bovina (TBb) é uma doença infecciosa crônica e progressiva causada pelo Mycobacterium bovis e uma importante zoonose em todo o mundo. O objetivo deste estudo foi realizar análises espaciais e temporais em um banco de dados secundário de casos positivos de TBb registrados pelo Serviço de Inspeção Federal em dois frigoríficos da mesorregião Oeste de Minas, estado de Minas Gerais, Brasil, de 2008 a 2012 e sugerir sua utilização na vigilância epidemiológica. Os bovinos abatidos com lesões macroscópicas de TBb durante a inspeção post mortem foram considerados positivos neste estudo. Os dados utilizados foram os casos positivos cadastrados no Sistema de Informações Gerenciais do Serviço de Inspeção Federal do Ministério da Agricultura, Pecuária e Abastecimento (SIGSIF/MAPA), o número de animais abatidos mensalmente e seus municípios de origem, por frigorífico. Foi calculada a prevalência (%) de casos por bovinos abatidos e avaliada a relação entre esses casos de TBb e os casos de tuberculose humana (TBh) e o PIB per capita das mesorregiões que compõem os municípios pesquisados. A prevalência foi de 1.030 casos de TBb (0,28%). Os menores números de casos e prevalências foram obtidos em 2010, enquanto as maiores prevalências foram observadas em 2011. O Frigorífico 1 apresentou estacionariedade, enquanto o Frigorífico 2 apresentou tendência anual crescente para os dados desde outubro de 2009. Correlação estatística entre o número de casos de TBb e TBh (p=0,006, r=0,148) foi observada. As prevalências nos Frigoríficos 1 e 2 não se correlacionaram (p>0,05). Os municípios de origem demonstraram aleatoriedade em sua distribuição espacial. O SIGSIF/MAPA pode ser utilizado para a análise da distribuição espacial e temporal a fim de contribuir com o monitoramento dos serviços de saúde animal com informações sobre a prevalência de condenações por TBb nas mesorregiões Oeste de Minas, Sul/Sudoeste de Minas, Campo das Vertentes e Zona da Mata de Minas Gerais, Brasil.(AU)

Spoligotyping, genotyping, and spatial distribution of Mycobacterium bovis in cattle in the state of Bahia, Brazil / Genotipagem por spoligotyping e distribuição espacial de Mycobacterium bovis em bovinos no estado da Bahia, Brasil

Mycobacterium bovis is responsible for bovine and buffalo tuberculosis, an important zoonotic disease with global distribution. The knowledge of the distribution and the precise identification of this disease, including advanced diagnoses such as spoligotyping, allows choosing the best strategies to fight the disease's progress. The present work aimed to investigate mycobacteria's presence, genotype their strains, and evaluate tuberculosis cases' spatial distribution from suggestive lesions in carcasses of bovine and buffalo inspected in slaughterhouses under an official inspection regime in the state of Bahia, Brazil. The study investigated 453,417 animals. Among these, 31 (0.007%) from 17 municipalities were suspected of tuberculosis. Among the culture medium growth, 95% of these were categorized as alcohol-acid resistant bacilli (BAAR). All isolates were subjected to spoligotyping and 95% were confirmed as M. bovis (SB0120, SB0121, SB0852, SB0828, SB0295, SB0881, SB1648, SB6119, SB0140, SB1055). The strain SB0120 was the most prevalent, and this profile has been described in cases of human tuberculosis by M. bovis, highlighting the zoonotic potential of this profile. This study also identified strains never reported in Bahia, highlighting a distinctive pattern from other parts of Brazil, besides mixed infections. Besides, to identify strains never before described in the state, highlighting a distinctive pattern in Brazil (SB6119 and SB0852, respectively). An unpublished profile was identified and inserted in the international database (Mbovis.org), named SB2715.(AU)

O Mycobacterium bovis é o responsável pela tuberculose bovina e bubalina, doença zoonótica importante e com distribuição global. O conhecimento da distribuição e a identificação precisa dessa enfermidade, incluindo diagnósticos mais avançados como o spoligotyping, permite escolher as melhores estratégias de combate ao avanço da doença. O presente trabalho objetivou investigar a presença de micobactérias, genotipar suas estirpes e avaliar a distribuição espacial dos casos de tuberculose a partir de lesões sugestivas nas carcaças de bovinos e bubalinos inspecionadas em frigoríficos sob regime de inspeção oficial no estado da Bahia. Foram investigados 453.417 animais dentre os quais 31 (0,007%) foram suspeitos de doença e provenientes de 17 municípios. Após o crescimento em meio de cultura, 95% foram categorizados como bacilos álcool-ácido resistentes (BAAR). Todos os isolados foram submetidos à spoligotyping e 95% foram confirmados M. bovis (SB0120, SB0121, SB0852, SB0828, SB0295, SB0881, SB1648, SB6119, SB0140, SB1055). A cepa SB0120 foi a mais prevalente e este perfil vem sendo descrito na literatura com casos de tuberculose humana por M. bovis ressaltando o potencial zoonótico deste perfil. Este estudo também identificou cepas nunca relatadas no estado da Bahia, destacando um padrão distinto de outras partes do Brasil, além da existência de infecções mistas. Permitiu ainda relatar linhagens nunca antes descritas no estado com destaque para um padrão novo no Brasil (SB6119 e SB0852 respectivamente). Um perfil inédito identificado foi identificado e inserido no banco de dados internacional (Mbovis.org), nomeado SB2715.(AU)

Bovine tuberculosis in safari park in Brazil / Tuberculose bovina em parque safári no Brasil

Bovine tuberculosis (bTB) is an infectious disease caused by Mycobacterium bovis, affecting domestic animals, wild animals and humans. In captivity, for wild animals, bTB represents a risk to animal keepers and zoo visitors, in addition to the possibility of spreading the infection to domestic animals or through the trade of infected wild animals. Sambar (Cervus unicolor), red deer (Cervus elaphus) and fallow deer (Dama dama) from a safari park in the State of Rio Grande do Sul, Brazil, showed a clinical condition of dyspnea and weight loss. Some animals died and showed lesions suggestive of tuberculosis (LST), which were confirmed by histopathology. After the interdiction of the safari park by the state veterinary authorities, 281 deer were euthanized with the authorization of the "Instituto Brasileiro do Meio Ambiente e dos Recursos Naturais Renováveis" (IBAMA). Retropharyngeal and submandibular lymph nodes and viscera were collected from 21 animals, which were grown in Stonebrink medium for up to 90 days. After DNA extraction from the bacterial colonies, PCR was performed for targets flanking the region of differentiation 4 (RD4). Of the 21 samples, 14 (66.7%) presented LST with a granulomatous appearance, a whitish coloration, and caseous or calcified consistency, and seven samples (33.3%), showed no lesions. In the culture of 14 samples with LST, 13 (92.8%) presented bacterial growth compatible with M. bovis. In the cultivation of the seven samples without LST, four (57.1%) presented colonies compatible with M. bovis. PCR and DNA sequencing of the PCR amplicons detected as positive all the 17 (100%) bacteriological cultures suggestive of M. bovis, thus confirming the outbreak of bTB in deer. Decisions about positive tested and suspicious animals should be taken based on the evaluation of the risk of transmission to the rest of the zoological animals, animal welfare, conservation considerations and, the zoonotic potential of this pathogen.(AU)

A tuberculose bovina (bTB) é uma doença infecciosa causada por Mycobacterium bovis, afetando animais domésticos, animais selvagens e humanos. Para animais selvagens em cativeiro, a bTB representa um risco para os tratadores de animais e visitantes do zoológico, além da possibilidade de espalhar a infecção para animais domésticos ou por meio do comércio de animais silvestres infectados. Cervídeos sambar (Cervus unicolor), veado-vermelho (Cervus elaphus) e gamo (Dama dama) de um parque safári no Estado do Rio Grande do Sul, Brasil, mostraram uma condição clínica de dispneia e perda de peso. Alguns animais morreram e apresentaram lesões sugestivas de tuberculose (LST), as quais foram confirmadas por histopatologia. Após a interdição do parque safári pelas autoridades veterinárias estaduais, 281 veados sofreram eutanásia com a autorização do Instituto Brasileiro do Meio Ambiente e dos Recursos Naturais Renováveis (IBAMA). Os linfonodos retrofaríngeos e submandibulares e vísceras foram coletados de 21 animais, que foram cultivados em meio Stonebrink por até 90 dias. Após extração de DNA das colônias bacterianas, foi realizada PCR para alvos que flanqueavam a região de diferenciação 4 (RD4). Das 21 amostras, 14 (66,7%) apresentaram LST com aspecto granulomatoso, coloração esbranquiçada e consistência caseosa ou calcificada, e sete amostras (33,3%) não apresentaram lesões. Na cultura de 14 amostras com LST, 13 (92,8%) apresentaram crescimento bacteriano compatível com M. bovis. No cultivo das sete amostras sem LST, quatro (57,1%) apresentaram colônias compatíveis com M. bovis. A PCR e o sequenciamento de DNA dos fragmentos de PCR detectaram como positivo todas as 17 (100%) culturas bacteriológicas sugestivas de M. bovis, confirmando assim o surto de bTB em cervídeos. As decisões sobre animais positivos testados e suspeitos devem ser tomadas com base na avaliação do risco de transmissão para o restante dos animais zoológicos, bem-estar animal, considerações de conservação e no potencial zoonótico desse patógeno.(AU)

Isolation and genotyping of Mycobacterium bovis in suggestive lesions of tuberculosis in cattle slaughtered in the state of Ceará, Brazil / Isolamento e tipificação genética de Mycobacterium bovis em lesões sugestivas de tuberculose em bovinos abatidos no estado do Ceará

Bovine tuberculosis (BTB) is a zoonosis caused by the bacterium Mycobacterium bovis, which induces the development of nodular and granulomatous lesions in various animal tissues. The recognition of these suggestive gross lesions during postmortem sanitary inspection in slaughterhouses provides a presumptive diagnosis, which requires the use of complementary tests to confirm the disease. This study aimed to verify the occurrence of BTB in cattle slaughtered in slaughterhouses in the state of Ceará, Brazil, using bacteriological and molecular methods. To this end, suggestive lesions were analyzed on carcasses condemned by the "Serviço de Inspeção Estadual" (SIE). The samples were submitted to microbiological analysis using culture media and specific staining followed by spoligotyping molecular technique for identification and genotyping of the mycobacteria. Occurrence of lesions suggestive of BTB was verified in bovine carcasses (0.071%) from different municipalities of the state. These lesions were located mainly in the lung (95.12%), lymph nodes (58.53%), and liver (36.58%). Microbiological culture showed bacterial isolation (17.94%), with the growth of colonies showing morphological and tannic characteristics belonging to genus Mycobacterium spp. Genetic polymorphism analysis identified M. bovis in all isolates, which were discriminated into six spoligotypes (SB0121, SB0295, SB1064, SB0120, SB0870, and SB0852). These profiles have been described in Brazil and several areas of the world, except for profiles SB1064 and SB0852, which were described in the country for the first time. The results show that the association of the diagnostic methods used was the basis for the first study on identification of mycobacteria found in the state, which may provide a database for the epidemiological study of BTB in the state of Ceará.(AU)

A tuberculose bovina (TB) é uma zoonose causada pelo Mycobacterium bovis, o qual induz ao desenvolvimento de lesões nodulares e granulomatosas em vários tecidos do animal. O reconhecimento dessas lesões macroscópicas sugestivas durante a inspeção sanitária post mortem em matadouros fornece um diagnóstico presuntivo, sendo necessário a utilização de testes complementares para confirmação da doença. O objetivo deste trabalho foi verificar a ocorrência da TB em animais abatidos em matadouros-frigoríficos no estado do Ceará através da utilização de métodos bacteriológicos e moleculares. Para tanto, foram analisadas lesões sugestivas de TB em carcaças condenadas pelo Serviço de Inspeção Estadual (SIE). As amostras foram submetidas à análise microbiológica, utilizando meios de cultivo e de coloração específicos, seguida pela técnica molecular spoligotyping para identificação e tipificação genética da micobactéria. Verificou-se a ocorrência de lesões sugestivas de TB em carcaças bovinas (0,071%) oriundas de diferentes municípios do estado do Ceará. Essas lesões estavam localizadas principalmente no pulmão (95,12%), linfonodos (58,53%) e fígado (36,58%). O cultivo microbiológico obteve isolamento bacteriano (17,94%), com o crescimento de colônias apresentando características morfológicas e tintoriais pertencentes ao gênero Mycobacterium spp. A análise do polimorfismo genético identificou a presença de M. bovis em todos os isolados, que foram discriminados em seis espoligotipos (SB0121, SB0295, SB1064, SB0120, SB0870 e SB0852), descritos no Brasil e em diversas áreas do mundo, exceto os perfis SB1064 e SB0852 que foram descritos pela primeira vez no país. Os resultados obtidos demonstram que a associação dos métodos diagnósticos utilizados foram a base do primeiro estudo de identificação das micobactérias encontradas no estado do Ceará, o que pode contribuir para a criação de um banco de dados para o estudo epidemiológico da TB no estado.(AU)

Characterisation of alternative expression vectors for recombinant Bacillus Calmette-Guérin as live bacterial delivery systems

BACKGROUND Bacillus Calmette-Guérin (BCG) is considered a promising live bacterial delivery system. However, several proposals for rBCG vaccines have not progressed, mainly due to the limitations of the available expression systems. OBJECTIVES To obtain a set of mycobacterial vectors using a range of promoters with different strengths based on a standard backbone, previously shown to be stable. METHODS Mycobacterial expression vectors based on the pLA71 vector as backbone, were obtained inserting different promoters (PAN, PαAg, PHsp60, PBlaF* and PL5) and the green fluorescence protein (GFP) as reporter gene, to evaluate features such as their relative strengths, and the in vitro (inside macrophages) and in vivo stability. FINDINGS The relative fluorescence observed with the different vectors showed increasing strength of the promoters: PAN was the weakest in both Mycobacterium smegmatis and BCG and PBlaF* was higher than PHsp60 in BCG. The relative fluorescence observed in a macrophage cell line showed that PBlaF* and PHsp60 were comparable. It was not possible to obtain strains transformed with the extrachromosomal expression vector containing the PL5 in either species. MAIN CONCLUSION We have obtained a set of potentially stable mycobacterial vectors with a arrange of expression levels, to be used in the development of rBCG vaccines.

Newly sequenced genomes of four Bacillus Calmette Guerin vaccines

Bacillus Calmette Guerin (BCG) vaccines comprise a family of related strains. Whole genome sequencing has allowed the better characterisation of the differences between many of the BCG vaccines. As sequencing technologies improve, updating of publicly available sequence data becomes common practice. We hereby announce the draft genome of four commonly used BCG vaccines in Brazil, Argentina and Venezuela.

Frequency of Mycobacterium tuberculosis Among M. tuberculosis Complex Strains Isolated from Clinical Specimen / 대한임상미생물학회지

BACKGROUND: Rapid and accurate detection of Mycobacterium tuberculosis (MTB) is of primary importance for infection control and selection of anti-tuberculosis drugs. However, most clinical laboratories report MTB complex (MTC) without reporting MTB because MTC comprising MTB, Mycobacterium bovis, Mycobacterium africanum, Mycobacterium microti, Mycobacterium caprae and Mycobacterium pinnipedii have 99.9% similarity at the nucleotide level and identical 16S rRNA sequences. This study was conducted to analyze the species frequency of MTC isolates obtained from clinical specimen.METHODS: Of 310 MTC isolates obtained from clinical samples in a tertiary care hospital from February 2017 to August 2018, MolecuTech Real TB-Taq (YD Diagnostics, Korea) real-time PCR was performed, specifically to detect MTB. For DNA showing MTB negative results by MTB-specific real-time PCR or pyrazinamide-resistant strains, PCR-based MTC typing, spoligotyping, and exact tandem repeat D gene sequencing were performed.RESULTS: All the 310 MTC isolates were identified to be MTB. Two MTB strains of East-African-Indian 4-Vietnam genotype, which have not been reported in Korea, were also found.CONCLUSION: There was no zoonotic tuberculosis in this study. Since we investigated only 310 MTC isolates detected in only one medical institution, multi-center study is needed to accurately know the prevalence of zoonotic tuberculosis in Korea.

Aspectos clínicos e terapêuticos de infecção por Mycobacterium bovis em gato doméstico - relato de caso / Clinical and therapeutic aspects of infection by Mycobacterium bovis in domestic cat - case report

Este artigo tem como objetivo relatar um caso de infecção por Mycobacterium bovis em um gato doméstico, com seis meses de idade, enfatizando seus aspectos clínicos e terapêuticos. O felino apresentava como histórico a ingestão de leite de vaca não fervido e posteriormente desenvolveu sinais de anorexia, tosse não produtiva e linfadenomegalia. Para elucidação do diagnóstico, foram realizados exames complementares de imagem, hematológicos, citológicos e reação em cadeia da polimerase (PCR). Diante da confirmação de infecção por Mycobacterium, o tratamento foi instituído por meio da associação de três antimicrobianos (enrofloxacino 5mg/kg, claritromicina 10mg/kg e rifampicina 15mg/kg), por via oral, a cada 12 horas, aos quais o animal respondeu positivamente, apresentando significativa diminuição dos sinais clínicos; entretanto, após 60 dias de tratamento, foi a óbito devido a um atropelamento. Conclui-se que a realização do tratamento em gatos com tuberculose pode ocasionar melhora dos sinais clínicos e que, embora de ocorrência rara no Brasil, essa enfermidade deve ser incluída como diagnóstico diferencial das enfermidades infecciosas nessa espécie.(AU)

This article aims to report a case of Mycobacterium bovis infection in a six-month-old domestic cat, emphasizing its clinical and therapeutic aspects. The feline presented as history the intake of unboiled cow's milk and later developed signs of anorexia, non-productive cough and lymphadenomegaly. Additional imaging, hematological, cytological and polymerase chain reaction (PCR) tests were performed to elucidate the diagnosis. In the presence of Mycobacterium infection, treatment was instituted by the combination of three antimicrobials (Enrofloxacin 5mg/kg, Clarithromycin 10mg/kg, and Rifampicin 15mg/kg) orally every 12 hours, to which the animal responded positively, presenting significant decrease of the clinical signs, however after 60 days of treatment the cat died accidentally, hit by a car on the street. It is concluded that the treatment in cats affected by tuberculosis can cause improvement of clinical signs and that although rare in Brazil, this disease should be included as a differential diagnosis of infectious diseases in this species.(AU)

Tuberculosis abdominal en niños de un hospital público de tercer nivel en México / Abdominal tuberculosis in children of a public tertiary hospital in Mexico

INTRODUCCIÓN. A nivel mundial la tuberculosis es una de las diez causas de muerte, con una incidencia de 7 920 pacientes entre 0 ­ 14 años en la región de América; siendo el abdomen el sitio extrapulmonar más común. OBJETIVOS. Describir las características etarias, clínicas, microbio-lógicas, complicaciones y comorbilidades asociadas en los pacientes pediátricos con tuberculosis abdominal. MATERIALES Y MÉTODOS. Estudio retrospectivo, base de datos de 23 pacientes y edades de 0 meses a 17 años 11 meses y 29 días de edad con evidencia confirmatoria de la presencia del microorganismo; de los servicios de Gastroenterología y Epidemiología en el Nuevo Hospital Civil de Guadalajara "Dr. Juan I. Menchaca ", período 2007 a 2018. RESULTADOS. Se informaron 47,8% (11; 23) de sexo masculino y 52,2% (12; 23) de sexo femenino; 26,1% (6; 23) con antecedente de ingesta de lácteos no pasteurizados. Los tres datos clínicos más frecuentes fueron dolor abdominal, fiebre y pérdida de peso. El 8,7% (2;23) tuvieron convivencia con personas con tuberculosis activa positivo; 30,4% (7; 23) registraron prueba cutánea de derivado proteico pu-rificado positiva; 30,4% (7; 23) identificación de bacterias ácido-alcohol resistentes positivo; 43,5% (10; 23) estudios de imagen compatibles; 8,7% (2; 23) proteína C reactiva de mucosa intestinal po-sitivo; 4,3% (1; 36) cultivo positivo y 8,7% (2; 23) pacientes con inmunodeficiencia. CONCLUSIÓN. La tuberculosis abdominal, se presentó en menores de edad con síntomas inespecíficos de dolor abdominal, fiebre y pérdida de peso, expuestos a ingesta de productos lácteos no pasteurizados, combe positivo e inmunodeficiencia.

INTRODUCTION. Worldwide, tuberculosis is one of the ten causes of death, with an incidence of 7 920 patients between 0 - 14 years in the Americas region; the abdomen being the most common extrapulmonary site. OBJECTIVES. Describe the age, clinical, microbiological, complications and associated comorbidities in pediatric patients with abdominal tuberculosis. MATERIALS AND ME-THODS. Retrospective study, database of 23 patients and ages from 0 months of age to 17 years 11 months and 29 days of age with confirmatory evidence of the presence of the microorganism; of the Gastroenterology and Epidemiology services at the New Civil Hospital of Guadalajara "Dr. Juan I. Menchaca ", period 2 007 to 2 018. RESULTS. 47,8% (11; 23) men and 52,2% (12; 23) women were reported; 26,1% (6; 23) with a history of unpasteurized dairy intake. The three most frequent clinical data were abdominal pain, fever and weight loss. 8,7% (2; 23) lived together with people with positive active tuberculosis; 30,4% (7; 23) recorded a positive purified protein derivative skin test; 30,4% (7; 23) positive acid-alcohol resistant bacteria identification; 43,5% (10; 23) compatible imaging studies; 8,7% (2; 23) positive intestinal mucosal C-reactive protein; 4,3% (1; 36) positive culture and 8,7% (2; 23) patients with immunodeficiency. CONCLUSION. Abdominal tuberculosis occurred in minors with nonspecific symptoms of abdominal pain, fever and weight loss, exposed to intake of unpasteurized dairy products, positive combe and immunodeficiency

Enfermedad por bacilo de Calmette-Guérin a distancia en un lactante: Presentación de un caso / Distant bacillus Calmette-Guérin disease in an infant: Case report

La vacuna con el bacilo de Calmette-Guérin es una vacuna atenuada utilizada para prevenir formas graves de tuberculosis. Se aplica a los recién nacidos en países con alta prevalencia de tuberculosis. Pueden presentarse, después de su aplicación, complicaciones a nivel local, como supuración o adenopatías regionales. La enfermedad por diseminación del bacilo es infrecuente y ocurre, por lo general, en pacientes con alteraciones inmunitarias subyacentes. Se presenta el caso de un niño de 5 meses que ingresó por un cuadro de 2 meses de evolución con detención del aumento de peso y nódulos subcutáneos. Se sospechó enfermedad por diseminación del bacilo y se diagnosticó por la biopsia de las lesiones. Se realizó el tratamiento con tres drogas antituberculosas, y se recuperó clínicamente. Si bien se realizaron estudios inmunológicos, no logró demostrarse ninguna inmunodeficiencia como afección predisponente.

The bacillus Calmette-Guérin vaccine is an attenuated vaccine historically used to prevent severe forms of tuberculosis. It is applied to all newborns in countries with high prevalence of tuberculosis. Local complications, such as suppuration or regional adenopathies, may occur after application. Disease due to the spread of the bacillus is infrequent, usually occurring in a patient with an underlying immune alteration. We present the case of a 5-month-old child who was admitted due to a 2-month evolution with weight loss and subcutaneous nodules. Disease was suspected to be due to bacillus Calmette-Guérin dissemination, being diagnosed by biopsy of the lesions. Treatment was carried out with three antituberculous drugs, evolving towards clinical recovery. Although immunological studies were carried out, no immunodeficiency could be demonstrated as a predisposing condition.

Tuberculosis por Mycobacterium bovis en un niño de la Comuna N° 8, Ciudad Autónoma de Buenos Aires / Mycobacterium bovis Tuberculosis in a child in the Commune n° 8, Buenos Aires City

La tuberculosis bovina es una enfermedad infectocontagiosa producida por Mycobacterium bovis, que, junto con otras micobacterias, compone el complejo Mycobacterium tuberculosis. Su prevención radica en detectar la infección en el ganado bovino y pasteurizar la leche. El hombre, clásicamente, ha adquirido la enfermedad por contacto con el ganado, en el contexto de una zoonosis laboral, o por consumo de productos lácteos no pasteurizados. Se describe el caso de un paciente de 10 años, sin actividades relacionadas con animales, que presenta una forma de tuberculosis pulmonar por M. bovis, indistinguible clínica y radiológicamente de la tuberculosis humana. Se destaca la importancia de la detección de la enfermedad, del control sanitario de los alimentos y del primer nivel de atención en lo que respecta al reconocimiento de la enfermedad y a su prevención en la población.

Bovine tuberculosis is a contagious infectious disease produced by Mycobacterium bovis, which together with other mycobacteria makes up the Mycobacterium tuberculosis complex. Its prevention lies in detection of the infection in cattle and milk pasteurization. Man has traditionally acquired the disease through contact with livestock, in the context of an occupational zoonosis, or through consumption of unpasteurized dairy products. We describe the case of a 10-year-old male patient, without activities related to animals, that presents a form of pulmonary tuberculosis due to M. bovis, clinically and radiologically indistinguishable from human tuberculosis. The importance of the disease detection, the food sanitary control, and the first level of attention, with respect to the recognition of the disease and its prevention in the population, is highlighted.

Tuberculose bovina: diagnóstico ante mortem e post mortem em bovinos leiteiros através da associação de análises / Bovine tuberculosis: diagnosis ante mortem and post mortem in dairy cattle through analysis association

Este estudo descreve o emprego de quatro métodos diagnósticos para a confirmação de casos de tuberculose em bovinos. Para tanto foram avaliados 211 bovinos leiteiros, dos quais 35,1% apresentaram reatividade no teste tuberculínico cervical comparativo, e 143 animais foram encaminhados para abate sanitário. No acompanhamento do abate e inspeção sanitária verificou-se que 51,8% dos bovinos apresentavam lesões visíveis compatíveis com tuberculose. Também foram coletados fragmentos teciduais de bovinos com e sem lesões macroscópicas, os quais na análise histológica apresentaram numerosas áreas de necrose caseosa e áreas de calcificação, e na coloração de Ziehl-Neelsen apresentaram bacilos álcool-ácido resistentes. Assim, as análises empregadas no estudo se mostraram importantes para o diagnóstico acurado de tuberculose bovina, além de alertar para o risco de saúde pública que pessoas que trabalham nos abatedouros e/ou em contato direto com bovinos doentes estão submetidas.

La importancia de investigar Mycobacterium bovis en muestras clínicas de procedencia humana / Importance of investigating Mycobacterium bovis in clinical samples of human origin

Resumen Introducción. La tuberculosis es una enfermedad infectocontagiosa que continúa siendo un problema mundial de salud pública. Es la principal causa de mortalidad en personas con HIV. Objetivo. Identificar la presencia de Mycobacterium bovis como agente etiológico de tuberculosis humana en muestras de esputo con baciloscopia positiva, mediante la prueba Genotype MTBC™. Materiales y métodos. Se llevó a cabo un estudio descriptivo de 88 muestras de esputo remitidas al Grupo de Micobacterias del Instituto Nacional de Salud entre enero y noviembre de 2015. Se hizo el análisis microbiológico convencional y se empleó la prueba molecular de Genotype MTBC™ para diferenciar las especies del complejo M. tuberculosis. Resultados. Sesenta y dos casos (70,5 %) correspondían a pacientes de sexo masculino; los grupos más afectados fueron el de 24 a 34 años, el de residentes en las cabeceras municipales, y el de afiliados al régimen subsidiado. En el 50 % (44) de las muestras con resultados en la prueba de identificación de la especie, se detectó el complejo M. tuberculosis. Conclusiones. La mayor carga de la enfermedad se registró en la población masculina y en edad productiva. La prueba de identificación para especies del complejo, solo demostró la presencia de M. tuberculosis. Sin embargo, con estos datos no es posible descartar M. bovis en humanos con tuberculosis en Colombia. La identificación diferencial de la especie debería implementarse de forma rutinaria en los casos de tuberculosis en los grupos de riesgo y en las zonas donde se conoce la circulación de esta micobacteria en bovinos.

Abstract Introduction: Tuberculosis is an infectious disease that still represents a major public health problem worldwide. It is one of the main causes of mortality in people with HIV. Objective: To identify the presence of M. bovis as an etiological agent of human tuberculosis in sputum smear positive samples using the test Genotype MTBC™. Materials and methods: We conducted a descriptive study, 88 sputum samples were submitted to the Grupo de Micobacterias of the Instituto Nacional de Salud between January and November, 2015. We used the conventional microbiological analysis and the molecular test Genotype MTBC™ to identify the M. tuberculosis complex species. Results: Sixty two (70.5%) were males; the most affected groups were those between 24 and 34 years old, those residing in the municipal seats and those affiliated to the subsidized health plans. In 50.0% (44) of the samples with a result in the species identification test, we detected M. tuberculosis. Conclusion: The highest burden of the disease was recorded among the male population in productive ages. The identification test for species of the complex showed all were M. tuberculosis. However, it is not possible to discard the presence of M. bovis in humans in Colombia. The differential identification of species should be done in risk groups and in areas where the circulation of this mycobacterium in cattle is known.

Interstitial cystitis - intravesical treatment

The Guidelines Project, an initiative of the Brazilian Medical Association, aims to combine information from the medical field in order to standardize producers to assist the reasoning and decision-making of doctors. The information provided through this project must be assessed and criticized by the physician responsible for the conduct that will be adopted, depending on the conditions and the clinical status of each patient.

The Necessity of a Nationwide Surveillance System of Serious BCG Adverse Reactions

No abstract available.

Mycobacterium bovis Osteitis Following Immunization with Bacille Calmette-Guérin (BCG) in Korea

BACKGROUND: Mycobacterium bovis Bacille Calmette-Guérin (BCG) osteitis, a rare complication of BCG vaccination, has not been well investigated in Korea. This study aimed to evaluate the clinical characteristics of BCG osteitis during the recent 10 years in Korea. METHODS: Children diagnosed with BCG osteitis at the Seoul National University Children's Hospital from January 2007 to March 2018 were included. M. bovis BCG was confirmed by multiplex polymerase chain reaction (PCR) in the affected bone. BCG immunization status and clinical information were reviewed retrospectively. RESULTS: Twenty-one patients were diagnosed with BCG osteitis and their median symptom onset from BCG vaccination was 13.8 months (range, 6.0–32.5). Sixteen children (76.2%) received Tokyo-172 vaccine by percutaneous multiple puncture method, while four (19.0%) and one (4.8%) received intradermal Tokyo-172 and Danish strain, respectively. Common presenting symptoms were swelling (76.2%), limited movement of the affected site (63.2%), and pain (61.9%) while fever was only accompanied in 19.0%. Femur (33.3%) and the tarsal bones (23.8%) were the most frequently involved sites; and demarcated osteolytic lesions (63.1%) and cortical breakages (42.1%) were observed on plain radiographs. Surgical drainage was performed in 90.5%, and 33.3% of them required repeated surgical interventions due to persistent symptoms. Antituberculosis medications were administered for a median duration of 12 months (range, 12–31). Most patients recovered without evident sequelae. CONCLUSION: Highly suspecting BCG osteitis based on clinical manifestations is important for prompt management. A comprehensive national surveillance system is needed to understand the exact incidence of serious adverse reactions following BCG vaccination and establish safe vaccination policy in Korea.

Bacille Calmette-Guérin Supply Disruption Emphasizes the Importance of Stewardship / La interrupción del suministro de bacilo de Calmette-Guérin subraya la importancia de la administración

Since the original trial published by Morales et al in 1976, intravesical Bacille Calmette-Guérin (BCG) has been a centerpiece in non-muscle invasive bladder cancer (NMIBC) treatment, with a rigorous induction and maintenance regimen shown to decrease cancer recurrence and progression.[1] [2] More than 50% of the 81,000 new cases of bladder cancer that are diagnosed each year in the United States (US) (550,000 in the world) are NMIBCs, and it is clear that effective and timely treatments like BCG are essential and must be readily available.

Desde el ensayo original publicado por Morales et al en 1976, el Bacilo de Calmette-Guérin (BCG) intravesical ha sido una pieza central en el tratamiento del cáncer de vejiga no músculo-invasivo (CCNMI), con un régimen riguroso de inducción y mantenimiento que ha demostrado disminuir la recurrencia y progresión del cáncer [1] [2]. [1] [2] Más del 50% de los 81.000 nuevos casos de cáncer de vejiga que se diagnostican cada año en Estados Unidos (550.000 en el mundo) son CCNMI, y está claro que los tratamientos eficaces y oportunos como el BCG son esenciales y deben estar fácilmente disponibles.