The impact of point mutations in the human androgen receptor : classification of mutations on the basis of transcriptional activity

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Serotype distribution of remaining pneumococcal meningitis in the mature PCV10/13 period: Findings from the PSERENADE Project

Pneumococcal conjugate vaccine (PCV) introduction has reduced pneumococcal meningitis incidence. The Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) project described the serotype distribution of remaining pneumococcal meningitis in countries using PCV10/13 for least 5-7 years with primary series uptake above 70%. The distribution was estimated using a multinomial Dirichlet regression model, stratified by PCV product and age. In PCV10-using sites (N = 8; cases = 1141), PCV10 types caused 5% of cases <5 years of age and 15% among ≥5 years; the top serotypes were 19A, 6C, and 3, together causing 42% of cases <5 years and 37% ≥5 years. In PCV13-using sites (N = 32; cases = 4503), PCV13 types caused 14% in <5 and 26% in ≥5 years; 4% and 13%, respectively, were serotype 3. Among the top serotypes are five (15BC, 8, 12F, 10A, and 22F) included in higher-valency PCVs under evaluation. Other top serotypes (24F, 23B, and 23A) are not in any known investigational product. In countries with mature vaccination programs, the proportion of pneumococcal meningitis caused by vaccine-in-use serotypes is lower (≤26% across all ages) than pre-PCV (≥70% in children). Higher-valency PCVs under evaluation target over half of remaining pneumococcal meningitis cases, but questions remain regarding generalizability to the African meningitis belt where additional data are needed

Footnotes to a war

Keith Windschuttle's book The Fabrication of Aboriginal History opened a fresh and ugly chapter in our "culture wars". Here, four writers look at what we've learned from a year of bitter debate

Clinical Features and Outcomes of Serotype 19A Invasive Pneumococcal Disease in Calgary, Alberta

BACKGROUND: Streptoccocus pneumoniae serotype 19A (ST19A) became an important cause of invasive pneumococcal disease (IPD) after the introduction of the conjugate vaccine.OBJECTIVE: To examine the severity and outcome of ST19A IPD compared with non-ST19A IPD.METHODS: The Calgary Area Streptococcus pneumoniae Epidemiology Research (CASPER) study collects clinical and laboratory data on all IPD cases in Calgary, Alberta. Analysis was performed on data from 2000 to 2010 comparing ST19A and non-ST19A IPD cases. Adjusted linear and logistic regression models were used to examine outcomes of duration of appropriate intravenous antibiotic therapy and intensive care unit admission, respectively.RESULTS: ST19A tended to cause disease in younger patients. ST19A isolates were more often multidrug resistant (19% versus 0.3%; Pud_less_than0.001). Adjusted logistic regression showed no difference in intensive care unit admission between ST19A and non-ST19A IPD cases (OR 1.4 [95% CI 0.8 to 2.7]). An adjusted linear regression model showed patients ud_less_than18 years of age with a diagnosis of bacteremia and no risk factors infected with ST19A were, on average, treated with antibiotics 1.4 times (95% CI 1.1 to 1.9) as long as patients with non-19A IPD and the same baseline characteristics.DISCUSSION: ST19A IPD was associated with an increase in average time on antibiotics. Although many of the infecting strains of ST19A were within the threshold for susceptibility, they may be sufficiently resilient to require a longer duration of antibiotic therapy or higher dose to clear the infection.CONCLUSIONS: ST19A is more common in younger individuals, is more antibiotic resistant and may require longer average treatment duration.Peer Reviewe

Factors influencing early and late mortality in adults with invasive pneumococcal disease in Calgary, Canada: A prospective surveillance study

Background Invasive pneumococcal disease continues to be an important cause of mortality. In Calgary, 60% of deaths occur within 5 days of presenting to hospital. This proportion has not changed since before the era of penicillin. The purpose of this study was to investigate what factors may influence death within 5 days of presentation with pneumococcal disease.Methods and Findings Demographic and clinical data from the CASPER (Calgary Area Streptococcus pneumoniae Epidemiology Research) study on 1065 episodes of invasive pneumococcal disease in adults (≥18 years) from 2000 to 2010 were analyzed. Adjusted multinomial regression was performed to analyze 3 outcomes: early mortality (Conclusions Presenting with severe invasive pneumococcal disease, multiple comorbidities, and older age increases the risk of both early and late death. Patients who died early often presented too late for effective antibiotic therapy, highlighting the need for an effective vaccine

PCR and Culture Analysis of Streptococcus pneumoniae Nasopharyngeal Carriage in Healthy Children

Invasive Streptococcus pneumoniae disease is preceded by asymptomatic nasopharyngeal carriage. Measuring carriage in healthy populations provides data on what serotypes are present in communities, which is of interest in the era of polyvalent pneumococcal conjugate vaccines. Nasopharyngeal swabs from a survey of 682 and 800 healthy children in 2016 and 2018, respectively, were analyzed by culture and Quellung reaction to determine rates of carriage and serotypes. All swabs from 2016 and 300 randomly selected swabs from 2018 were then analyzed using real-time semi-quantitative PCR (qPCR) to detect S. pneumoniae gene targets lytA, piaA, and SP2020 and determine serotype. There were 71 (10.4%) and 68 (8.5%) culture positive samples in 2016 and 2018, respectively. All of these were also positive by qPCR except one that was equivocal. In total, 46.0% of 2016 swabs were positive by qPCR. In 2018, results from the selected sample extrapolated to the complete sample showed 49.0% positive by qPCR. PCV13 serotypes were detected in 29.3% and 21.7% of S. pneumoniae qPCR positive samples from 2016 and 2018, respectively; compared with only 8.4% and 6.0% PCV13 serotypes detected by Quellung reaction in culture positive samples. Compared with culture, qPCR detected S. pneumoniae more frequently. Further, qPCR serotyping detected PCV13 serotypes in a larger proportion of samples than culture and Quellung reaction did, showing that, despite established universal childhood PCV13 immunization, vaccine serotypes can still be detected in a large proportion of young children.Medicine, Faculty ofNon UBCPediatrics, Department ofReviewedFacultyResearche