Impact of 13-Valent Pneumococcal Conjugate Vaccine on Colonization and Invasive Disease in Cambodian Children

Background Cambodia introduced the 13-valent pneumococcal conjugate vaccine (PCV13) in January 2015 using a 3 + 0 dosing schedule and no catch-up campaign. We investigated the effects of this introduction on pneumococcal colonization and invasive disease in children aged <5 years. Methods There were 6 colonization surveys done between January 2014 and January 2018 in children attending the outpatient department of a nongovernmental pediatric hospital in Siem Reap. Nasopharyngeal swabs were analyzed by phenotypic and genotypic methods to detect pneumococcal serotypes and antimicrobial resistance. Invasive pneumococcal disease (IPD) data for January 2012–December 2018 were retrieved from hospital databases. Pre-PCV IPD data and pre-/post-PCV colonization data were modelled to estimate vaccine effectiveness (VE). Results Comparing 2014 with 2016–2018, and using adjusted prevalence ratios, VE estimates for colonization were 16.6% (95% confidence interval [CI] 10.6–21.8) for all pneumococci and 39.2% (95% CI 26.7–46.1) for vaccine serotype (VT) pneumococci. There was a 26.0% (95% CI 17.7–33.0) decrease in multidrug-resistant pneumococcal colonization. The IPD incidence was estimated to have declined by 26.4% (95% CI 14.4–35.8) by 2018, with a decrease of 36.3% (95% CI 23.8–46.9) for VT IPD and an increase of 101.4% (95% CI 62.0–145.4) for non-VT IPD. Conclusions Following PCV13 introduction into the Cambodian immunization schedule, there have been declines in VT pneumococcal colonization and disease in children aged <5 years. Modelling of dominant serotype colonization data produced plausible VE estimates

Single-dose administration and the influence of the timing of the booster dose on immunogenicity and efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine: a pooled analysis of four randomised trials.

BACKGROUND: The ChAdOx1 nCoV-19 (AZD1222) vaccine has been approved for emergency use by the UK regulatory authority, Medicines and Healthcare products Regulatory Agency, with a regimen of two standard doses given with an interval of 4-12 weeks. The planned roll-out in the UK will involve vaccinating people in high-risk categories with their first dose immediately, and delivering the second dose 12 weeks later. Here, we provide both a further prespecified pooled analysis of trials of ChAdOx1 nCoV-19 and exploratory analyses of the impact on immunogenicity and efficacy of extending the interval between priming and booster doses. In addition, we show the immunogenicity and protection afforded by the first dose, before a booster dose has been offered. METHODS: We present data from three single-blind randomised controlled trials-one phase 1/2 study in the UK (COV001), one phase 2/3 study in the UK (COV002), and a phase 3 study in Brazil (COV003)-and one double-blind phase 1/2 study in South Africa (COV005). As previously described, individuals 18 years and older were randomly assigned 1:1 to receive two standard doses of ChAdOx1 nCoV-19 (5 × 1010 viral particles) or a control vaccine or saline placebo. In the UK trial, a subset of participants received a lower dose (2·2 × 1010 viral particles) of the ChAdOx1 nCoV-19 for the first dose. The primary outcome was virologically confirmed symptomatic COVID-19 disease, defined as a nucleic acid amplification test (NAAT)-positive swab combined with at least one qualifying symptom (fever ≥37·8°C, cough, shortness of breath, or anosmia or ageusia) more than 14 days after the second dose. Secondary efficacy analyses included cases occuring at least 22 days after the first dose. Antibody responses measured by immunoassay and by pseudovirus neutralisation were exploratory outcomes. All cases of COVID-19 with a NAAT-positive swab were adjudicated for inclusion in the analysis by a masked independent endpoint review committee. The primary analysis included all participants who were SARS-CoV-2 N protein seronegative at baseline, had had at least 14 days of follow-up after the second dose, and had no evidence of previous SARS-CoV-2 infection from NAAT swabs. Safety was assessed in all participants who received at least one dose. The four trials are registered at ISRCTN89951424 (COV003) and ClinicalTrials.gov, NCT04324606 (COV001), NCT04400838 (COV002), and NCT04444674 (COV005). FINDINGS: Between April 23 and Dec 6, 2020, 24 422 participants were recruited and vaccinated across the four studies, of whom 17 178 were included in the primary analysis (8597 receiving ChAdOx1 nCoV-19 and 8581 receiving control vaccine). The data cutoff for these analyses was Dec 7, 2020. 332 NAAT-positive infections met the primary endpoint of symptomatic infection more than 14 days after the second dose. Overall vaccine efficacy more than 14 days after the second dose was 66·7% (95% CI 57·4-74·0), with 84 (1·0%) cases in the 8597 participants in the ChAdOx1 nCoV-19 group and 248 (2·9%) in the 8581 participants in the control group. There were no hospital admissions for COVID-19 in the ChAdOx1 nCoV-19 group after the initial 21-day exclusion period, and 15 in the control group. 108 (0·9%) of 12 282 participants in the ChAdOx1 nCoV-19 group and 127 (1·1%) of 11 962 participants in the control group had serious adverse events. There were seven deaths considered unrelated to vaccination (two in the ChAdOx1 nCov-19 group and five in the control group), including one COVID-19-related death in one participant in the control group. Exploratory analyses showed that vaccine efficacy after a single standard dose of vaccine from day 22 to day 90 after vaccination was 76·0% (59·3-85·9). Our modelling analysis indicated that protection did not wane during this initial 3-month period. Similarly, antibody levels were maintained during this period with minimal waning by day 90 (geometric mean ratio [GMR] 0·66 [95% CI 0·59-0·74]). In the participants who received two standard doses, after the second dose, efficacy was higher in those with a longer prime-boost interval (vaccine efficacy 81·3% [95% CI 60·3-91·2] at ≥12 weeks) than in those with a short interval (vaccine efficacy 55·1% [33·0-69·9] at <6 weeks). These observations are supported by immunogenicity data that showed binding antibody responses more than two-fold higher after an interval of 12 or more weeks compared with an interval of less than 6 weeks in those who were aged 18-55 years (GMR 2·32 [2·01-2·68]). INTERPRETATION: The results of this primary analysis of two doses of ChAdOx1 nCoV-19 were consistent with those seen in the interim analysis of the trials and confirm that the vaccine is efficacious, with results varying by dose interval in exploratory analyses. A 3-month dose interval might have advantages over a programme with a short dose interval for roll-out of a pandemic vaccine to protect the largest number of individuals in the population as early as possible when supplies are scarce, while also improving protection after receiving a second dose. FUNDING: UK Research and Innovation, National Institutes of Health Research (NIHR), The Coalition for Epidemic Preparedness Innovations, the Bill & Melinda Gates Foundation, the Lemann Foundation, Rede D'Or, the Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca

Distinct features of rabbit and human adipose-derived mesenchymal stem cells: implications for biotechnology and translational research

Helena Debiazi Zomer,1,2 Kelly CS Roballo,2 Thais Borges Lessa,2 Fabiana Fernandes Bressan,2 Nat&aacute;lia Nardeli Gon&ccedil;alves,2 Fl&aacute;vio Vieira Meirelles,2,3 Andrea Gon&ccedil;alves Trentin,1 Carlos Eduardo Ambr&oacute;sio2,3 1Department of Cell Biology, Embryology and Genetic, Faculty of Biological Sciences, Santa Catarina Federal University (UFSC), Florian&oacute;polis, Brazil; 2Department of Surgery, Sector Anatomy, Faculty of Veterinary Medicine and Animal Science, University of S&atilde;o Paulo, S&atilde;o Paulo, Brazil; 3Department of Veterinary Medicine, Faculty of Animal Science and Food Engineering, University of S&atilde;o Paulo, S&atilde;o Paulo, Brazil Introduction: Owing to their similarity with humans, rabbits are useful for multiple applications in biotechnology and translational research from basic to preclinical studies. In this sense, mesenchymal stem cells (MSCs) are known for their therapeutic potential and promising future in regenerative medicine. As many studies have been using rabbit adipose-derived MSCs (ASCs) as a model of human ASCs (hASCs), it is fundamental to compare their characteristics and understand how distinct features could affect the translation to human medicine.Objective: The aim of this study was to comparatively characterize rabbit ASCs (rASCs) and hASCs to further uses in biotechnology and translational studies.Materials and methods: rASCs and hASCs were isolated and characterized by their immunophenotype, differentiation potential, proliferative profile, and nuclear stability in vitro.Results and discussion: Both ASCs presented differentiation potential to osteocytes, chondrocytes, and adipocytes and shared similar immunophenotype expression to CD105+, CD34&ndash;, and CD45&ndash;, but rabbit cells expressed significantly lower CD73 and CD90 than human cells. In addition, rASCs presented greater clonogenic potential and proliferation rate than hASCs but no difference in nuclear alterations.Conclusion: The distinct features of rASCs and hASCs can positively or negatively affect their use for different applications in biotechnology (such as cell reprogramming) and translational studies (such as cell transplantation, tissue engineering, and pharmacokinetics). Nevertheless, the particularities between rabbit and human MSCs should not prevent rabbit use in preclinical models, but care should be taken to interpret results and properly translate animal findings to medicine.Keywords: characterization, comparison, MSC, iPS, immunophenotype, proliferation&nbsp

Associação entre indicadores antropométricos de obesidade e risco coronariano em adultos na cidade de Salvador, Bahia, Brasil Association of anthropometric indicators of obesity with coronary risk in adults in the city of Salvador, Bahia, Brazil

OBJETIVO: O estudo teve como objetivo determinar a associação entre os diversos indicadores de obesidade e risco coronariano elevado (RCE) em adultos na cidade de Salvador-BA. MÉTODOS: O desenho foi de corte transversal, com amostra composta por 968 adultos de 30-74 anos de idade, sendo 391 (40.4%) homens. A análise constou da regressão logística, sendo calculadas as Odds Ratio (OR) entre o índice de conicidade (índice C), índice de massa corporal (IMC), razão circunferência cintura-quadril (RCCQ), circunferência de cintura (CC) e RCE. Utilizou-se intervalo de confiança a 95%. RESULTADOS: Após ajustamento por idade, as OR encontradas para homens foram: a) RCCQ: 5.81 (3.00-11.23), b) índice C: 5.52 (2.94-10.36), c) CC: 4.37 (2.31-8.26), d) IMC: 3.04 (1.62-5.73). Para mulheres dos 30 aos 49 anos e 50 aos 74 anos as OR encontradas foram, respectivamente: a) RCCQ: 7.85 (2.15-28.69) e 1.81 (0.98-3.36); b) IMC: 7.28 (1.61-32.97) e 1.09 (0.61-1.96); c) índice C: 6.88 (1.89 -25.11) e 2.89 (1.58-5.27); d) CC: 6.41 (2.09-19.65) e 1.38 (0.77-2.50). CONCLUSÕES: Os resultados demonstram que, entre homens e mulheres de 30-49 anos, todos os indicadores de obesidade apresentam forte associação com RCE, destacando-se entre os homens os indicadores de obesidade central, RCCQ e IC, enquanto que para as mulheres entre 50 e 74 anos o índice C é o melhor indicador.<br>OBJECTIVE: To determine the association between the many anthropometric indicators of obesity and high coronary risk (HCR). METHODS: This is a cross-sectional study. Its population comprised 968 adults, 30-74 years of age, of which 391 (40.4%) were men. Logistic regression analysis was used and the Odds Ratio (OR) was calculated between the conicity index (C index), body mass index (BMI), waist-to-hip ratio (WHR), waist circumference (WC), and HCR. A 95% confidence interval was utilized. RESULTS: The OR between obesity indicators and HCR, adjusted by age, in men were: a) WHR - 5.81 (3.00-11.23), b) C index - 5.52 (2.94-10.36), c) WC - 4.37 (2.31-8.26), d) BMI - 3.04 (1.62-5.73). In women 30-49 years old and 50-74 years old the OR adjusted by age, respectively, were: a) WHR - 7.85 (2.15-28.69) and 1.81 (0.98-3.36), b) BMI - 7.28 (1.61-32.97) and 1.09 (0.61-1.96), c) C index - 6.88 (1.89 -25.11) and 2.89 (1.58-5.27), d) WC - 6.41 (2.09-19.65) and 1.38 (0.77-2.50). CONCLUSION: Both in men and women, 30-49 years old, all obesity indicators are strongly associated with HCR. However, WHR and C index were found to be the most effective in male individuals, while C index was the best indicator in women from 50 to 74 years of age

Diet of the gracile mouse opossum Gracilinanus agilis (Didelphimorphia: Didelphidae) in a neotropical savanna: intraspecific variation and resource selection.

Investigation of the effect of endogenous and exogenous factors on the diet of animals is necessary for a better understanding of their feeding habits. This approach can provide relevant information on the autoecology of a species and its ecological interactions. We investigated the composition and intraspecific variation in the diet of the marsupial Gracilinanus agilis in areas of dry woodland forests (i.e., cerradão) in the Cerrado of Central Brazil, taking into consideration the availability of prey (arthropods) in the environment. We found insects, spiders, birds, and fruits in the scats of G. agilis. Insects (orders Hymenoptera, Isoptera, Hemiptera, and Coleoptera) and fruits were the most frequently consumed resources. Males fed more heavily on insects than females did, whereas during the warm?wet season (October to April), the reproductive females fed on insects more than the nonreproductive females did. On the other hand, the consumption of fruits and vertebrates did not vary between seasons, sexes, or according to female reproductive condition. Moreover, reproductive females fed more frequently on ants and beetles than nonreproductive females did. We also detected both positive (for Isoptera and Hemiptera) and negative (for Hymenoptera) selection of insects during the cool?dry season, whereas in the warm?wet season, these resources were consumed according to their availability in the environment. Our study revealed that G. agilis is an insectivore?omnivore species, but fruits also are a relevant part of its diet. This marsupial seemed to select their prey qualitatively according to its energy demands and nutritional requirements