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A significant reduction in invasive pneumococcal disease (IPD) has been reported, across all ages, following the implementation of 7-valent conjugate pneumococcal vaccine (PCV7) globally, as part of infant immunization programs. We explored the additional impact of PCV13 on IPD over a 14-year period. Using provincial laboratory surveillance and hospitalization data (N = 5791), we calculated the annual incidence of IPD following the implementation of PCV13 vaccine. Poisson regression was used to evaluate changes in the overall incidence of IPD, and serotype-specific IPD between PCV7 (2004-10) and PCV13 (2011-2015) eras. Overall, IPD rates have seen a modest decline in the PCV13 compared to the PCV7 era (IRR 0.84; 95% CI: 0.79-0.89); this was seen in children ≤2 years of age, and the majority of the adult cohort. Rates of vaccine-type IPD (PCV7 and PCV13) also decreased in the PCV13 era. In contrast, IPD incidence related to non-PCV13 (IRR: 1.56; 95%CI:1.43-1.72) and non-vaccine serotypes (IRR: 2.12; 95%CI:1.84-2.45) increased in the PCV13 era compared to the PCV7 era. A modest reduction in IPD from the PCV13 vaccine was observed, with gains limited to the immunized cohort and adults. However, a significant increase in non-vaccine serotypes emphasizes the need for continued surveillance.

Norway and black rats (Rattus norvegicus and Rattus rattus) are among the most ubiquitous urban wildlife species and are the source of a number of zoonotic diseases responsible for significant human morbidity and mortality in cities around the world. Rodent ecology is a primary determinant of the dynamics of zoonotic pathogens in rodent populations and the risk of pathogen transmission to people, yet many studies of rat-associated zoonoses do not account for the ecological characteristics of urban rat populations. This hinders the development of an in-depth understanding of the ecology of rat-associated zoonoses, limits comparability among studies, and can lead to erroneous conclusions. We conducted a year-long trapping-removal study to describe the ecological characteristics of urban rat populations in an inner-city neighborhood of Vancouver, Canada. The study focused on factors that might influence the ecology of zoonotic pathogens in these populations and/or our understanding of that ecology. We found that rat population density varied remarkably over short geographical distances, which could explain observed spatial distributions of rat-associated zoonoses and have implications for sampling and data analysis during research and surveillance. Season appeared to influence rat population composition even within the urban environment, which could cause temporal variation in pathogen prevalence. Body mass and bite wounds, which are often used in epidemiologic analyses as simple proxies for age and aggression, were shown to be more complex than previously thought. Finally, we found that factors associated with trapping can determine the size and composition of sampled rat population, and thus influence inferences made about the source population. These findings may help guide future studies of rats and rat-associated zoonoses.

Myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) is a syndrome of unknown etiology characterized by profound fatigue exacerbated by physical activity, also known as post-exertional malaise (PEM). Previously, we did not detect evidence of immune dysregulation or virus reactivation outside of PEM periods. Here we sought to determine whether cardiopulmonary exercise stress testing of ME/CFS patients could trigger such changes. ME/CFS patients (n = 14) and matched sedentary controls (n = 11) were subjected to cardiopulmonary exercise on 2 consecutive days and followed up to 7 days post-exercise, and longitudinal whole blood samples analyzed by RNA-seq. Although ME/CFS patients showed significant worsening of symptoms following exercise versus controls, with 8 of 14 ME/CFS patients showing reduced oxygen consumption ([Formula: see text]) on day 2, transcriptome analysis yielded only 6 differentially expressed gene (DEG) candidates when comparing ME/CFS patients to controls across all time points. None of the DEGs were related to immune signaling, and no DEGs were found in ME/CFS patients before and after exercise. Virome composition (P = 0.746 by chi-square test) and number of viral reads (P = 0.098 by paired t-test) were not significantly associated with PEM. These observations do not support transcriptionally-mediated immune cell dysregulation or viral reactivation in ME/CFS patients during symptomatic PEM episodes.

Four cluster randomized controlled trials (cRCTs) conducted in long-term care facilities (LTCFs) have reported reductions in patient risk through increased healthcare worker (HCW) influenza vaccination. This evidence has led to expansive policies of enforcement that include all staff of acute care hospitals and other healthcare settings beyond LTCFs. We critique and quantify the cRCT evidence for indirect patient benefit underpinning policies of mandatory HCW influenza vaccination. Plausibility of the four cRCT findings attributing indirect patient benefits to HCW influenza vaccination was assessed by comparing percentage reductions in patient risk reported by the cRCTs to predicted values. Plausibly predicted values were derived according to the basic mathematical principle of dilution, taking into account HCW influenza vaccine coverage and the specificity of patient outcomes for influenza. Accordingly, predicted values were calculated as a function of relevant compound probabilities including vaccine efficacy (ranging 40-60% in HCWs and favourably assuming the same indirect protection conferred through them to patients) × change in proportionate HCW influenza vaccine coverage (as reported by each cRCT) × percentage of a given patient outcome (e.g. influenza-like illness (ILI) or all-cause mortality) plausibly due to influenza virus. The number needed to vaccinate (NNV) for HCWs to indirectly prevent patient death was recalibrated based on real patient data of hospital-acquired influenza, with adjustment for potential under-detection (5.2-fold), and using favourable assumptions of HCW-attributable risk (ranging 60-80%). In attributing patient benefit to increased HCW influenza vaccine coverage, each cRCT was found to violate the basic mathematical principle of dilution by reporting greater percentage reductions with less influenza-specific patient outcomes (i.e., all-cause mortality > ILI > laboratory-confirmed influenza) and/or patient mortality reductions exceeding even favourably-derived predicted values by at least 6- to 15-fold. If extrapolated to all LTCF and hospital staff in the United States, the prior cRCT-claimed NNV of 8 would implausibly mean >200,000 and >675,000 patient deaths, respectively, could be prevented annually by HCW influenza vaccination, inconceivably exceeding total US population mortality estimates due to seasonal influenza each year, or during the 1918 pandemic, respectively. More realistic recalibration based on actual patient data instead shows that at least 6000 to 32,000 hospital workers would need to be vaccinated before a single patient death could potentially be averted. The four cRCTs underpinning policies of enforced HCW influenza vaccination attribute implausibly large reductions in patient risk to HCW vaccination, casting serious doubts on their validity. The impression that unvaccinated HCWs place their patients at great influenza peril is exaggerated. Instead, the HCW-attributable risk and vaccine-preventable fraction both remain unknown and the NNV to achieve patient benefit still requires better understanding. Although current scientific data are inadequate to support the ethical implementation of enforced HCW influenza vaccination, they do not refute approaches to support voluntary vaccination or other more broadly protective practices, such as staying home or masking when acutely ill.

This retrospective cohort study is the first in North America to examine population-level appropriate antibiotic use for community-acquired pneumonia (CAP) in older adults, by agent, dose and duration. With the highest rates of CAP reported in the elderly populations, appropriate antibiotic use is essential to improve clinical outcomes. Given the ongoing crisis of antimicrobial resistance, understanding inappropriate antibiotic prescribing is integral to direct community stewardship efforts. All outpatient primary care visits for CAP (aged [greater than or equal to]65 years) were identified using physician billing codes between January 1 2014 to December 31 2018 in British Columbia (BC) and Ontario (ON). Categories of prescribing were derived from existing literature, and constructed for clinical relevance using Canadian and international guidelines available during the study period. Categories were mutually exclusive and included: guideline adherent (first-line agent, adherent dose/duration), clinically appropriate (non-first line agent, presence of comorbidities), effective but unnecessary (first-line agent, excess dose/duration), undertreatment (first-line agent, subtherapeutic dose/duration), and not recommended (non-first line agent, absence of comorbidities). Proportions of prescribing were examined by category. Temporal trends in prescribing were examined using Poisson regression. A total of 436,441 episodes of CAP were identified, with 46% prescribed an antibiotic in BC, and 52% in Ontario. Guideline adherent prescribing was minimal for both provinces (BC: 2%; ON: 1%) however the largest magnitude of increase was reported in this category by the final study year (BC-Rate Ratio [RR]: 3.4, 95% Confidence Interval [CI]: 2.7-4.3; ON-RR: 4.62, 95% CI: 3.4-6.5). Clinically appropriate prescribing accounted for the most antibiotics issued, across all study years (BC: 61%; ON: 74%) (BC-RR: 0.8, 95% CI: 0.8-0.8; ON-RR: 0.9, 95% CI: 0.8-0.9). Excess duration of therapy was the hallmark characteristic for effective but unnecessary prescribing (BC: 92%; ON: 99%). The most common duration prescribed was 7 days, followed by 10. Not recommended prescribing was minimal in both provinces (BC: 4%; ON: 7%) and remained stable by the final study year (BC-RR: 1.1, 95% CI: 0.9-1.2; ON-RR: 0.9, 95% CI: 0.9-1.1). Three quarters of antibiotic prescribing for CAP was appropriate in Ontario, but only two thirds in BC. Shortening durations-in line with evidence for 3 to 5-day treatment presents a focused target for stewardship efforts.

Information on factors that influence parental decisions for actual human papillomavirus (HPV) vaccine receipt in publicly funded, school-based HPV vaccine programs for girls is limited. We report on the level of uptake of the first dose of the HPV vaccine, and determine parental factors associated with receipt of the HPV vaccine, in a publicly funded school-based HPV vaccine program in British Columbia, Canada. All parents of girls enrolled in grade 6 during the academic year of September 2008-June 2009 in the province of British Columbia were eligible to participate. Eligible households identified through the provincial public health information system were randomly selected and those who consented completed a validated survey exploring factors associated with HPV vaccine uptake. Bivariate and multivariate analyses were conducted to calculate adjusted odds ratios to identify the factors that were associated with parents' decision to vaccinate their daughter(s) against HPV. 2,025 parents agreed to complete the survey, and 65.1% (95% confidence interval [CI] 63.1-67.1) of parents in the survey reported that their daughters received the first dose of the HPV vaccine. In the same school-based vaccine program, 88.4% (95% CI 87.1-89.7) consented to the hepatitis B vaccine, and 86.5% (95% CI 85.1-87.9) consented to the meningococcal C vaccine. The main reasons for having a daughter receive the HPV vaccine were the effectiveness of the vaccine (47.9%), advice from a physician (8.7%), and concerns about daughter's health (8.4%). The main reasons for not having a daughter receive the HPV vaccine were concerns about HPV vaccine safety (29.2%), preference to wait until the daughter is older (15.6%), and not enough information to make an informed decision (12.6%). In multivariate analysis, overall attitudes to vaccines, the impact of the HPV vaccine on sexual practices, and childhood vaccine history were predictive of parents having a daughter receive the HPV vaccine in a publicly funded school-based HPV vaccine program. By contrast, having a family with two parents, having three or more children, and having more education was associated with a decreased likelihood of having a daughter receive the HPV vaccine. This study is, to our knowledge, one of the first population-based assessments of factors associated with HPV vaccine uptake in a publicly funded school-based program worldwide. Policy makers need to consider that even with the removal of financial and health care barriers, parents, who are key decision makers in the uptake of this vaccine, are still hesitant to have their daughters receive the HPV vaccine, and strategies to ensure optimal HPV vaccine uptake need to be employed.