SUPLEMENTAÇÃO COM Bacillus toyonensis MODULA A PRODUÇÃO DE ANTICORPOS EM CAMUNDONGOS SENSIBILIZADOS COM ANTÍGENOS DE Leishmania (Leishmania) infatum chagasi

The aim of this study was to evaluate the effect of supplementation with the probiotic Bacillus toyonensis on the production of IgG, IgG1 and IgG2a antibodies against Leishmania (Leishmania) infantum chagasi antigens. Twenty-four female albino BALB/c mice, 21 days old, were immunized experimentally against L. (L.) infantum chagasi, divided into three experimental groups. Group A received no supplementation, group B was continuously supplemented until day 56 and in group C the probiotic was administered seven days before and seven days after each immunization for the same period. The experiment was conducted until day 84. Seroconversion was used to evaluate the humoral immune response. During the supplementation, all the animals presented total IgG seroconversion against the antigen used, without statistical difference (p>0.05) between the groups. In the isotype analysis, the group supplemented with probiotic in the continuous period presented seroconversion results of the upper IgG2a / IgG1 ray when compared to the control group (1.8 times) and to that supplemented seven days before and seven days after supplementation (1.2 times) on day 70, keeping their titre superior to the groups in question until the end of the experiment (1.2 times on day 84). Based on these results, it can observed a greater ability of the supplemented group to continuously modulate favorably the humoral immune response and to maintain the production of IgG2a isotype antibodies against the antigen in question.Keywords: Canine leishmaniasis; probiotic; immune response.O estudo teve como objetivo avaliar o efeito da suplementação com o probiótico Bacillus toyonensis na cinética da produção de anticorpos IgG, IgG1 e IgG2a contra antígenos de Leishmania (Leishmania) infatum chagasi. Foram utilizados 24 camundongos BALB/c, fêmeas, tendo em média 21 dias de idade, sensibilizados experimentalmente contra L. (L.) infantum chagasi, divididos em três grupos experimentais. O grupo A não recebeu suplementação, o grupo B foi suplementado de forma contínua até o dia 56 e no grupo C o probiótico foi administrado sete dias antes e sete dias após cada sensibilização, pelo mesmo período. O experimento foi conduzido até o dia 84. Foi utilizada a soroconversão para avaliação da resposta imune humoral. Durante a suplementação todos os animais apresentaram soroconversão de IgG total contra o antígeno utilizado, sem ser identificada diferença estatística (p<0,05) entre os grupos. Na análise de isotipagem, o grupo suplementado com probiótico no período contínuo apresentou resultados de soroconversão da razão IgG2a/IgG1 superior quando comparado ao grupo controle (1,8 vezes) e ao suplementado sete dias antes e sete dias após a suplementação (1,2 vezes) no dia 70, mantendo o seu título superior aos grupos em questão até o final do experimento (1,2 vezes no dia 84). Com base nesses resultados, pode-se observar maior habilidade do grupo suplementado continuamente modular favoravelmente a resposta imune humoral e manter a produção de anticorpos do isotipo IgG2a contra o antígeno em questão.Palavras-chave: Leishmaniose canina, probiótico, resposta imunológica

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK.

BACKGROUND: A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. METHODS: This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. FINDINGS: Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0-75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4-97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8-80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3-4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. INTERPRETATION: ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials. FUNDING: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, Bill & Melinda Gates Foundation, Lemann Foundation, Rede D'Or, Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK

Background A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. Methods This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. Findings Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0–75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4–97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8–80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3–4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. Interpretation ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Characterization and evaluation of cross reactivity of strains of streptococcus equi recovered from horses in Southern Rio Grande do Sul, Brazil

Streptococcus equi is the causative agent of strangles, one of the most widespread and costly horse diseases. The disease is highly contagious, and common symptoms are fever and lynphadenitis with abscesses in the neck region. Vaccines against strangles have been used but do not confer efficient protection against infection with Streptococcus equ i. In this paper, Strains of Streptococcus equi recovered from thirty-five horses with clinical Strangles in southern Rio Grande do Sul, Brazil, were characterized. Monovalent inactivated vaccines were produced with the strains. Groups of isogenic Balb/c mice were vaccinated on days 0 and 14 with the vaccines and with two commercial vaccines for strangles. Blood samples were collected on days 0, 14, 28, 56 and 70. Antibodies were titrated through ELISA using homologous and heterologous antigens, and Cross Reactivy Indices estimated. Thirteen strains of S. equi were recovered from the thirty-five samples studied. Five of them produced acid from some of the carbohydrates used, behaving as atypical strains. Four of these only metabolised the carbohydrate when equine serum was added. Cross Reactivity Indices showed that the strains studied belonged to the same serogroup. Cross Reactivity Indices among the strains recovered and the vaccines, on the contrary, varied from 23 to 46, showing very low reactivity among them.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESStreprococcus equi é o agente causador da Adenite eqüina, uma das mais disseminadas e comuns enfermidades que acomete eqüinos. Essa doença altamente contagiosa apresenta como principais sinais clínicos febre e linfoadenite com formação de abscessos na região de garganta. Vacinas contra a enfermidade tem sido usadas, mas não conferem proteção eficiente contra o agente. No presente trabalho foram caracterizadas 13 cepas de Streptococcus equi isoladas de materiais provenientes de 35 eqüinos com manifestações clínicas de Adenite Equina na região sul do Rio Grande do Sul. Prepararam-se vacinas monovalentes com as cepas de S. equi isoladas. Camundongos Balb/c isogênicos foram vacinados com as vacinas produzidas e com duas vacinas comerciais para garrotilho nos dias 0 e 14. Coletaram-se amostras de sangue nos dias 0, 14, 28 e 56. Titularam-se anticorpos pelo teste de ELISA, e estimaram-se os índices de reatividade cruzada. De 35 amostras coletadas, 13 foram de S. equi, das quais cinco produziram ácido a partir de algum açúcar, comportando-se como cepas atípicas. Destas, quatro só fermentaram açúcares em meio enriquecido com soro eqüino inativado. Os IRC demonstraram que as cepas de S. equi estudadas pertencem a um mesmo sorogrupo, entanto os IRC das vacinas comerciais variaram de 23 a 46 com as cepas de campo, demonstrando baixa reatividade