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Objective To describe variables used by Saudi pediatric intensivists to make antibiotic-related decisions for children with suspected severe bacterial infections. Methods We conducted a cross-sectional survey, which was developed using a multi-step methodological approach. The survey included 4 clinical scenarios of the most relevant bacterial infections in pediatric critical care (pneumonia, sepsis, meningitis and intra-abdominal infection). The potential determinants of antibiotic treatment duration addressed in all scenarios included clinical variables (patient characteristics, disease severity), laboratory infection markers, radiologic findings, and pathogens. Results The response rate was 65% (55/85). Eight variables (immunodeficiency, 3 months of age, 2 or more organ dysfunctions, Pediatric Risk of Mortality III score >10, leukocytosis, elevated C-reactive protein [CRP], elevated erythrocyte sedimentation rate [ESR], and elevated procalcitonin [PCT]) were associated with prolonging antibiotic treatment duration for all 4 clinical scenarios, with a median increase ranging from 3.0 days (95% confidence interval [CI] 0.5, 3.5, leukocytosis) to 8.8 days (95% CI 5.5, 10.5, immunodeficiency). There were no variables that were consistently associated with shortening antibiotic duration across all scenarios. Lastly, the proportion of physicians who would continue antibiotics for ≥5 days despite a positive viral polymerase chain reaction test result was 67% for pneumonia, 85% for sepsis, 63% for meningitis, and 95% for intra-abdominal infections. Conclusion Antibiotic-related decisions for critically ill patients are complex and depend on several factors. Saudi pediatric intensivists will use prolonged courses of antibiotics for younger patients, patients with severe clinical picture, and patients with persistently elevated laboratory markers and hospital acquired infections, even when current literature and guidelines do not suggest such practices. Antimicrobial stewardship programs should include interventions to address these misconceptions to ensure the rational use of antibiotics in pediatric intensive care units.

On March 3, 2021, faced with ongoing morbidity and mortality from coronavirus disease 2019 (COVID-19) and insufficient supplies of authorized, available vaccines against COVID-19 in Canada, the National Advisory Committee on Immunization (NACI) issued a strong recommendation to allow for an extended interval between vaccine doses to maximize the number of people protected as quickly as possible. NACI's recommendation was released in the form of a rapid response because of the urgency of the situation and was based on a review of the evidence; principles of immunology; historical experience with vaccines; modelling studies; and consideration of ethics, equity, feasibility, and acceptability. Since then, many questions and concerns have been raised. This article aims to provide further explanation of the rationale for the decision and prepare health care providers with information they need as they support their patients in the vaccination rollout.Le 3 mars 2021, devant la morbidité et la mortalité continues causées par la maladie à coronavirus 2019 (COVID-19) et l’offre insuffisante de vaccins autorisés et disponibles contre la COVID-19 au Canada, le Comité consultatif national de l’immunisation a publié une forte recommandation préconisant un intervalle prolongé entre les doses des vaccins, afin d’optimiser le nombre de personnes protégées le plus rapidement possible. La recommandation du comité, qui a pris la forme d’une réponse rapide en raison de l’urgence de la situation, repose sur l’examen des données probantes, les principes immunologiques, l’expérience des vaccins, les études de modélisation et les principes d’éthique, d’équité, de faisabilité et d’acceptabilité. De nombreuses questions et inquiétudes ont été soulevées depuis. Le présent article vise à mieux expliquer les motifs de cette recommandation et à fournir aux dispensateurs de soins l’information dont ils ont besoin pour soutenir leurs patients pendant le déploiement de la vaccination.

Le 3 mars 2021, devant la morbidité et la mortalité continues causées par la maladie à coronavirus 2019 (COVID-19) et l’offre insuffisante de vaccins autorisés et disponibles contre la COVID-19 au Canada, le Comité consultatif national de l’immunisation a publié une forte recommandation préconisant un intervalle prolongé entre les doses des vaccins, afin d’optimiser le nombre de personnes protégées le plus rapidement possible. La recommandation du comité, qui a pris la forme d’une réponse rapide en raison de l’urgence de la situation, repose sur l’examen des données probantes, les principes immunologiques, l’expérience des vaccins, les études de modélisation et les principes d’éthique, d’équité, de faisabilité et d’acceptabilité. De nombreuses questions et inquiétudes ont été soulevées depuis. Le présent article vise à mieux expliquer les motifs de cette recommandation et à fournir aux dispensateurs de soins l’information dont ils ont besoin pour soutenir leurs patients pendant le déploiement de la vaccination.

BACKGROUND In North America, the first dose of a measles-containing vaccine (MCV1) is administered at ≥12 months of age. However, MCV1 may be given to infants

Summary Background Many immigrants are susceptible to varicella on arrival to Canada because of different transmission dynamics in their countries of origin and scarcity of vaccination. Universal childhood vaccination programmes decrease varicella incidence rates through herd immunity, but the accumulating number of susceptible adult immigrants could remain at risk for severe varicella. Our aim was to describe the epidemiology of varicella among immigrants and non-immigrants before and after childhood varicella vaccination. Methods We did a population-based, retrospective cohort study of all varicella cases in Quebec, Canada, diagnosed between 1996 and 2014 in administrative health databases linked to immigration data. Cases of varicella met diagnostic codes in the International Classification of Diseases, Ninth and Tenth Revision Canadian modifications. Cases with a co-occurring zoster diagnostic code and immigrants from Australia, New Zealand, the USA, and western European countries were excluded. Vaccination periods included pre-vaccination (1996–98), private vaccination (1999–2005), and public vaccination (2006–14). Incidence rate and comparative rate ratios were estimated using census data. Findings A total of 231 339 varicella cases diagnosed between Jan 1, 1996, and Dec 31, 2014, were linked to 1 115 696 immigrants who arrived between Jan 1, 1980, and Dec 31, 2014. 1444 herpes zoster cases and 1276 immigrants from Australia, western Europe, New Zealand, and the USA were excluded. Among 228 619 varicella cases, 13 315 (5·8%) occurred in immigrants. In pre-vaccination versus public vaccination periods, varicella incidence declined in immigrants by 87% (95% CI 86·6–87·9; 324·3 cases per 100 000 person-years to 40·9 cases per 100 000 person-years) and in non-immigrants by 93% (92·4–92·7; 484 cases per 100 000 person-years to 36 cases per 100 000 person-years). Mean age at diagnosis increased in both groups (15·1 vs 19·4 years in immigrants and 8·4 vs 12·0 years in non-immigrants). In the public vaccination period, immigrants younger than 50 years had higher varicella rates than non-immigrants, with relative risk ranging from 1·53 (95% CI 1·37–1·72) to 4·64 (3·90–5·53) with the highest risk in adolescents and young adults, and people from Latin America and the Caribbean (age-specific incidence rate ratio [aIRR]I-NI pre-vaccination 2·19 and post-vaccination aIRRI-NI6·07) and south Asia (aIRRI-NI pre-vaccination 3·41 and aIRRI-NI post-vaccination 4·46) and in childbearing women (15–40 years; IRRI-NI 2·48). Interpretation Immigrant adolescents, young adults, and women of childbearing age had higher age-standardised rates of varicella than non-immigrants, with increasing disparities following vaccine introduction. Immigrants younger than 50 years of age would benefit from targeted vaccination upon arrival to host countries. Funding The Canadian Institutes of Health Research and The Department of Medicine, Jewish General Hospital, Montreal, QC, Canada.

Accurate serologic tests to detect host antibodies to SARS-CoV-2 will be critical for the public health response to the COVID-19 pandemic. This article discusses key use cases for SARS-CoV-2 antibo...

A vaccine for respiratory syncytial virus (RSV) has been actively sought for over 60 years due to the health impacts of RSV disease in infants, but currently the only available preventive measure in Canada and elsewhere is limited to passive immunization for high-risk infants and children with a monoclonal antibody. RSV vaccine development has faced many challenges, including vaccine-induced enhancement of RSV disease in infants. Several key developments in the last decade in the fields of cellular immunology and protein structure have led to new products entering late-stage clinical development. As of July 2019, RSV vaccine development is being pursued by 16 organizations in 121 clinical trials. Five technologies dominate the field of RSV vaccine development, four active immunizing agents (live-attenuated, particle-based, subunit-based and vector-based vaccines) and one new passive immunizing agent (monoclonal antibody). Phase 3 clinical trials of vaccine candidates for pregnant women, infants, children and older adults are under way. The next decade will see a dramatic transformation of the RSV prevention landscape.

Emergency vaccination programs often are needed to control outbreaks of meningococcal disease caused by Neisseria meningitidis serogroup B (MenB) on college campuses. Such campaigns expend multiple campus and public health resources. We conducted a randomized, controlled, multicenter, observer-blinded trial comparing immunogenicity and tolerability of an accelerated vaccine schedule of 0 and 21 days to a longer interval of 0 and 60 days for 4-component MenB vaccine (MenB-4C) in students 17-25 years of age. At day 21 after the first MenB-4C dose, we observed protective human serum bactericidal titers >4 to MenB strains 5/99, H44/76, and NZ 98/254 in 98%-100% of participants. Geometric mean titers increased >22-fold over baseline. At day 180, >95% of participants sustained protective titers regardless of their vaccine schedule. The most common adverse event was injection site pain. An accelerated MenB-4C immunization schedule could be considered for rapid control of campus outbreaks.

Impact of an adolescent tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine program was assessed in the provinces of British Columbia and Quebec, Canada. In both provinces, the Tdap booster has been in place since 2004, targeting Grade 9 students (14-15-years-of-age). Incidence rate ratios (IRRs) standardizing notification rates among teens 15-19-years-old to infants

Introduction Seasonal influenza is an important cause of morbidity and mortality, despite being vaccine-preventable. Sex factors (genes and hormones) seem to impact individuals’ susceptibility to infectious diseases and their response to vaccination. However, most vaccine studies do not explicitly assess sex differences in vaccine response, but rather adjust for sex. Methods We conducted a systematic review to analyze immunogenicity, efficacy, effectiveness and/or safety of seasonal influenza vaccine data stratified by sex. We searched PubMed, EMBASE, CINAHL, Web of Science and clinicaltrials.gov for observational studies and phase III/IV trials from January 1990 to June 2018, published in English or French. Two reviewers independently screened all references, then proceeded to data extraction and quality assessment using the Cochrane tools (RoB and ROBINS-I) on included studies. Results Of the 5,745 citations retrieved, 46 studies were included in the SR. Overall, 18 studies assessed immunogenicity, 1 estimated efficacy, 6 measured effectiveness and 25 evaluated safety of seasonal influenza vaccine in females and males (four studies reported on two sex-stratified outcomes concomitantly). Conclusion No clear conclusion could be drawn regarding the effect of sex on the immunogenicity and effectiveness of seasonal influenza vaccine, but higher rates of adverse events following immunization (AEFIs) were reported in females. The heterogeneity of data and studies’ low quality prevented us from conducting a meta-analysis. There is a need to emphasize on the appropriate use of the terms sex and gender in biomedical research. Evidence of higher quality is needed to better understand sex differences in response to influenza vaccine.

Studies of acute gastroenteritis (AGE) are hampered by the lack of routine diagnostic methods with good sensitivity and specificity. Molecular methods are increasingly used for clinical purposes, but the clinical significance of a positive result remains a challenge. In this study we aimed to compare results of routine diagnostic methods and molecular methods in symptomatic children and asymptomatic controls.Patients presenting to the pediatric emergency departments of two university hospitals in Brussels with AGE were recruited prospectively from May 2015 to October 2016; asymptomatic controls were recruited from the same hospitals. Stool analyses were performed for all participants for common pathogenic bacteria (culture), virus (immunochromatography) and parasites (microscopy). Stools were also analysed with the Luminex Gastrointestinal Pathogen Panel, a multiplex-PCR for common enteropathogens.Stools from 178 patients and 165 controls were analysed. An enteropathogen was detected in 62.4% (111/178) of cases when combining the two methods (56.2% (100/178) by Luminex, 42.7% (76/178) with routine methods) and 29.1% (48/165) of controls (24.2% (40/165) by Luminex and 10.3% (17/165) by routine methods). Some pathogens were detected more often with Luminex than with routine methods, such as Salmonella (16.3% (29/178) with Luminex and 3.9% (7/178) with routine method, p 0.05), whereas others identified by culture methods, such as Campylobacter, Shigella, Yersinia, were missed by Luminex.Molecular tools seem attractive methods, providing high positivity and a rapid turn-around time for the diagnosis of AGE. However, high rates of positivity in both cases and controls highlight the difficulty in interpreting results. Pathogens missed by Luminex but detected by culture methods raise more questions about the true clinical interest of the technique for our patients.

Urinary tract infections caused by the bacterium Escherichia coli are among the most frequently encountered infections and are a common reason for antimicrobial prescriptions. Resistance to fluoroquinolone antimicrobial agents, particularly ciprofloxacin, has increased in recent decades. It is intuitive that variation in fluoroquinolone resistance is driven by changes in antimicrobial use, but careful study of this association requires the use of time-series methods. Between April 2010 and December 2014, we studied seasonal variation in resistance to ciprofloxacin, trimethoprim-sulfamethoxazole, and ampicillin in community-acquired urinary E. coli isolates in Montreal, Quebec, Canada. Using dynamic linear models, we investigated whether seasonal variation in resistance could be explained by seasonal variation in community antimicrobial use. We found a positive association between total fluoroquinolone use lagged by 1 and 2 months and the proportion of isolates resistant to ciprofloxacin. Our results suggest that resistance to ciprofloxacin is responsive to short-term variation in antimicrobial use. Thus, antimicrobial stewardship campaigns to reduce fluoroquinolone use, particularly in the winter when use is highest, are likely to be a valuable tool in the struggle against antimicrobial resistance.

BACKGROUND The use of bacterial multiplex polymerase chain reaction (PCR) in children with suspected pertussis sometimes yields unexpected positive results for Mycoplasma pneumoniae. We aimed to evaluate the clinical significance of positive M. pneumoniae results in this population. METHODS Retrospective cohort of consecutive patients with suspected pertussis tested with a bacterial multiplex PCR (including Bordetella pertussis and M. pneumoniae) between June 2015 and March 2017. Medical records were reviewed to compare demographics, clinical presentations and outcomes of patients positive for M. pneumoniae with those positive for B. pertussis and those with negative results, using multivariable logistic regression. RESULTS A total of 1244 patients were included as follows: 56 (4.5%) with M. pneumoniae, 116 (9.3%) with B. pertussis and 1029 (82.7%) with negative results. Mean age was respectively 4.8 years, 6.5 years and 2.8 years (P < 0.05). Children with M. pneumoniae were less likely to present with cardinal symptoms of pertussis such as paroxysmal cough [adjusted odds ratio (OR): 0.19, 95% confidence interval (CI): 0.08-0.40) but were more likely to have fever (adjusted OR: 10.53, 95% CI: 3.54-39.49) and other nonspecific respiratory symptoms compared with children with B. pertussis. Children with M. pneumoniae had very similar clinical presentations to those with a negative PCR, but were more likely to have radiologically confirmed pneumonia (adjusted OR: 5.48, 95% CI: 2.96-9.99) and were less likely to be diagnosed with a concomitant viral infection (adjusted OR: 0.32, 95% CI: 0.07-0.99). CONCLUSIONS In children with suspected pertussis, the detection of M. pneumoniae is clinically relevant. However, the impact of this finding on patients' outcome is still unclear.

Key Points Question What is the seroprevalence of SARS-CoV-2 antibodies in a convenience sample of children aged 2 to 17 years in Montreal, Canada, enrolled between October 2020 and March 2021? Findings In this cohort study of 1632 participants, the mean baseline seroprevalence of SARS-CoV-2 was 5.8%. Of the 95 participants who were seropositive for SARS-CoV-2 antibodies, 82% were not tested or tested negative, and all experienced either mild or no clinical symptoms. Meaning The findings suggest that there was more transmission occurring in children compared with what was being detected, although children experienced few or mild symptoms., This cohort study estimates the seroprevalence of SARS-CoV-2 antibodies in children and teenagers in 4 neighborhoods of Montreal, Canada., Importance Quebec prioritized in-person learning after the first wave of the COVID-19 pandemic, with school closures being implemented temporarily in selected schools or in hot-spot areas. Quebec’s decision to keep most schools open was controversial, especially in Montreal, which was the epicenter of Canada’s first and second waves; therefore, understanding the extent to which children were infected with SARS-CoV-2 provides important information for decisions about school closures. Objective To estimate the seroprevalence of SARS-CoV-2 antibodies in children and teenagers in 4 neighborhoods of Montreal, Canada. Design, Setting, and Participants This cohort study (the Enfants et COVID-19: Étude de séroprévalence [EnCORE] study) enrolled a convenience sample of children aged 2 to 17 years between October 22, 2020, and March 22, 2021, in Montreal, Canada. Exposures Potential exposure to SARS-CoV-2. Main Outcomes and Measures The main outcome was seroprevalence of SARS-CoV-2 antibodies, collected using dried blood spots (DBSs) and analyzed with a research-based enzyme-linked immunosorbent assay (ELISA). Parents also completed an online questionnaire that included questions on self-reported COVID-19 symptoms and tests, along with sociodemographic questions. Results This study included 1632 participants who provided a DBS sample from 30 day cares, 22 primary schools, and 11 secondary schools. The mean (SD) age of the children who provided a DBS sample was 9.0 (4.4) years; 801 (49%) were female individuals, with 354 participants (22%) from day cares, 725 (44%) from primary schools, and 553 (34%) from secondary schools. Most parents had at least a bachelor’s degree (1228 [75%]), and 210 (13%) self-identified as being a racial or ethnic minority. The mean seroprevalence was 5.8% (95% CI, 4.6%-7.0%) but increased over time from 3.2% (95% CI, 0.7%-5.8%) in October to November 2020 to 8.4% (95% CI, 4.4%-12.4%) in March to April 2021. Of the 95 children with positive SARS-CoV-2 antibody results, 78 (82%) were not tested or tested negative with reverse transcription–polymerase chain reaction (RT-PCR) testing, and all experienced mild (49 [52%]) or no clinical symptoms (46 [48%]). The children of parents who self-identified as belonging to a racial and ethnic minority group were more likely to be seropositive compared with children of White parents (adjusted seroprevalence ratio, 1.9; 95% CI, 1.1-2.6). Conclusions and Relevance These results provide a benchmark of the seroprevalence status in Canadian children. The findings suggest that there was more transmission occurring in children compared with what was being detected by RT-PCR, although children experienced few or mild symptoms. It will be important to continue monitoring the serological status of children, particularly in the context of new COVID-19 variants of concern and in the absence of mass vaccination campaigns targeting young children.

BackgroundWe evaluated the use of rapid antigen detection tests (RADT) for the diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in school settings to determine RADT’s performance compared to PCR.MethodsIn this real-world, prospective observational cohort study, high-school students and staff were recruited from two high-schools in Montreal (Canada) and followed from January 25th to June 10th, 2021. Twenty-five percent of asymptomatic participants were tested weekly by RADT (nasal) and PCR (gargle). Class contacts of cases were tested. Symptomatic participants were tested by RADT (nasal) and PCR (nasal and gargle). The number of cases and outbreaks were compared to other high schools in the same area.ResultsOverall, 2,099 students and 286 school staff members consented to participate. The overall RADT’s specificity varied from 99.8 to 100%, with a lower sensitivity, varying from 28.6% in asymptomatic to 83.3% in symptomatic participants. Secondary cases were identified in 10 of 35 classes. Returning students to school after a 7-day quarantine, with a negative PCR on D6-7 after exposure, did not lead to subsequent outbreaks. Of cases for whom the source was known, 37 of 57 (72.5%) were secondary to household transmission, 13 (25%) to intra-school transmission and one to community contacts between students in the same school.ConclusionRADT did not perform well as a screening tool in asymptomatic individuals. Reinforcing policies for symptom screening when entering schools and testing symptomatic individuals with RADT on the spot may avoid subsequent significant exposures in class.Table of Contents SummaryRapid antigen tests were compared to standard PCR to diagnose SARS-CoV-2 infections in high-school students. They performed better in symptomatic individuals.What’s Known on This SubjectRapid antigen detection tests (RADT) are often used to diagnose respiratory pathogens at the point-of-care. Their performance characteristics vary, but they usually have high specificity and moderate sensitivity compared with PCR.What This Study AddsRADT sensitivity ranged from 28.6% in asymptomatic individuals to 83.3% in symptomatic individuals. Return to school after 7 days of quarantine was safe in exposed students. Secondary cases were identified in 28% of classes with an index case.

OBJECTIVES To determine the association between the implementation of an antimicrobial stewardship program at a local PICU and to determine the association between the presence of an antimicrobial stewardship programs and antimicrobial use across three Canadian PICUs, among critically ill children with bronchiolitis. DESIGN A multicenter retrospective cohort study. SETTING Three Canadian PICUs over two winter seasons. INTERVENTIONS An antimicrobial stewardship program was implemented at PICU 1 at the end of season 1. PATIENTS Patients less than or equal to 2 years old admitted with bronchiolitis. MEASUREMENTS AND MAIN RESULTS We used regression models with an interaction term between site (PICU 1 and PICU 2) and season (1 and 2) as the primary analysis to determine the association between implementation of an antimicrobial stewardship program at PICU 1 and 1) the proportion of antimicrobials discontinued 72 hours after hospital admission (logistic regression), 2) antimicrobial treatment duration (negative binomial regression), and 3) antimicrobial prescriptions within 48 hours of hospital admission (logistic regression). As a secondary analysis, we determined the association between having an antimicrobial stewardship program present and the aforementioned outcomes across the three PICUs. A total of 372 patients were included. During seasons 1 and 2, median age was 2.2 months (interquartile range, 1.2-6.2 mo) and 2.1 months (interquartile range, 1.3-6.8 mo), respectively. Among patients with viral bronchiolitis, implementation of an antimicrobial stewardship program at PICU 1 was associated with increased odds of discontinuing antimicrobials (odds ratio, 25.63; 95% CI, 2.86-326.29), but not with antimicrobial duration (odds ratio, 0.56; 95% CI, 0.31-1.02) or antimicrobial prescriptions (odds ratio, 0.33; 95% CI, 0.10-1.04). The presence of an antimicrobial stewardship program was similarly associated with antimicrobial discontinuation among patients with viral bronchiolitis (odds ratio, 20.79; 95% CI, 2.46-244.92), but not with antimicrobial duration (odds ratio, 0.57; 95% CI, 0.32-1.03) or antimicrobial prescriptions (odds ratio, 0.37; 95% CI, 0.12-1.11). CONCLUSIONS Antimicrobial stewardship programs were associated with increased likelihood of discontinuing antimicrobial treatments in the PICU patients with viral bronchiolitis. However, larger studies are needed to further determine the role of an antimicrobial stewardship programs in reducing unnecessary antimicrobial use in this patient population.

SignificanceThe primary method of COVID-19 detection is reverse transcription polymerase chain reaction (RT-PCR) testing. PCR test sensitivity may decrease as more variants of concern arise.AimWe aimed to develop a reagent-free way to detect COVID-19 in a real-world setting with minimal constraints on sample acquisition.ApproachWe present a workflow for collecting, preparing and imaging dried saliva supernatant droplets using a non-invasive, label-free technique – Raman spectroscopy – to detect changes in the molecular profile of saliva associated with COVID-19 infection.ResultsUsing machine learning and droplet segmentation, amongst all confounding factors, we discriminated between COVID-positive and negative individuals yielding receiver operating coefficient (ROC) curves with an area under curve (AUC) of 0.8 in both males (79% sensitivity, 75% specificity) and females (84% sensitivity, 64% specificity). Taking the sex of the saliva donor into account increased the AUC by 5%.ConclusionThese findings may pave the way for new rapid Raman spectroscopic screening tools for COVID-19 and other infectious diseases.

Background Invasive pneumococcal disease (IPD) burden, evaluated in Canada using reported confirmed cases in surveillance systems, is likely underestimated due to underreporting. We estimated the burden of IPD in Ontario and British Columbia (BC) by combining surveillance data with health administrative databases. Methods We established a cohort of 27,525 individuals in Ontario and BC. Laboratory-confirmed IPD cases were identified from Ontario’s integrated Public Health Information System and the BC Centre for Disease Control Public Health Laboratory. Possible IPD cases were identified from hospitalization data in both provinces, and from emergency department visit data in Ontario. We estimated the age and sex adjusted annual incidence of IPD and pneumococcal conjugate/polysaccharide vaccine (PCV/PPV) serotype-specific IPD using Poisson regression models. Results In Ontario, 20,205 overall IPD cases, including 15,299 laboratory-confirmed cases, were identified with relatively stable age- and sex-adjusted annual incidence rates ranging from 13.7/100,000 (2005) to 13.6/100,000 (2018). In BC, 7,320 overall IPD cases, including 5,932 laboratory-confirmed cases were identified; annual incidence rates increased from 10.9/100,000 (2002) to 13.2/100,000 (2018). Older adults aged ≥ 85 years had the highest incidence rates. During 2007–2018 the incidence of PCV7 serotypes and additional PCV13 serotypes decreased while the incidence of unique PPV23 and non-vaccine serotypes increased in both provinces. Conclusions IPD continues to cause a substantial public health burden in Canada despite publicly funded pneumococcal vaccination programs, resulting in part from an increase in unique PPV23 and non-vaccine serotypes.

IntroductionFurther evidence is needed to understand the contribution of schools and daycares for the spread of COVID-19 in the context of diverse transmission dynamics and continually evolving public health interventions. The Enfants et COVID-19: Étude de séroprévalence (EnCORE) study will estimate the seroprevalence and seroconversion of SARS-CoV-2 among school and daycare children and personnel. In addition, the study will examine associations between seroprevalence and sociodemographic characteristics and reported COVID-19 symptoms and tests, and investigates changes in health, lifestyle and well-being outcomes.Methods and analysisThis study includes children and personnel from 62 schools and daycares in four neighbourhoods in Montreal, Canada. All children aged 2–17 years attending one of the participating schools or daycares and their parents are invited to participate, as well as a sample of personnel members. Participants respond to brief questionnaires and provide blood samples, collected via dried blood spot, at baseline (October 2020–March 2021) and follow-up (May–June 2021). Questionnaires include sociodemographic and household characteristics, reported COVID-19 symptoms and tests, potential COVID-19 risk factors and prevention efforts and health and lifestyle information. Logistic regression using generalised estimating equations will be used to estimate seroprevalence and seroconversion, accounting for school-level clustering.Ethics and disseminationThis study was approved by the research ethics boards of the Université de Montréal (CERSES) and the Centre Hospitalier Universitaire Sainte-Justine. Results will contribute to our knowledge about SARS-CoV-2 transmission in schools and daycares and will be made available to study participants and their families, school and public health decision-makers and the research community.

Introduction: Chloroquine (CQ) and hydroxychloroquine (HCQ) are currently used for the prevention/treatment of malaria, and treatment of systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA). Although present data do not show their efficacy to treat COVID-19, they have been used as potential treatments for COVID-19. Given that pregnant women are excluded from randomized controlled trials, and present evidence are inconsistent and inconclusive, we aimed to investigate the safety of CQ or HCQ use in a large pregnancy cohort using real-world evidence.Methods: Using Quebec Pregnancy Cohort, we identified women who delivered a singleton liveborn, 1998–2015, (n = 233,748). The exposure time window for analyses on prematurity and low birth weight (LBW) was the second/third trimesters; was any time during pregnancy; only first trimester exposure was considered for analyses on major congenital malformations (MCM). The risk of prematurity, LBW, and MCM (overall and organ-specific) were quantified using generalized estimation equations.Results: We identified 288 pregnancies (0.12%) exposed to CQ (183, 63.5%) or HCQ (105, 36.5%) that resulted in liveborn singletons; CQ/HCQ was used for RA (17.4%), SLE (16.3%) or malaria (0.7%). CQ/HCQ was used for 71.8 days on average [standard-deviation (SD) 70.5], at a dose of 204.3 mg/d (SD, 155.6). We did not observe any increased risk related to CQ/HCQ exposure for prematurity (adjusted odds ratio [aOR] 1.39, 95%CI 0.84–2.30), LBW (aOR 1.11, 95%CI 0.59–2.06), or MCM (aOR 1.01, 95%CI 0.67–1.52).Conclusion: in this large CQ/HCQ exposed pregnancy cohort, we saw no clear increased risk of prematurity, LBW, or MCM, although number of exposed cases remained low.

Introduction Although a vaccine-preventable disease, influenza causes approximately 3–5 million cases of severe illness and about 290,000–650,000 deaths worldwide, which occur primarily among people 65 years and older. Nonetheless, prevention of influenza and its complications rely mainly on vaccination. We aimed to systematically evaluate influenza vaccine effectiveness at reducing healthcare utilization in older adults, defined as the reduction of outpatient visits, ILI and influenza hospitalizations, utilization of antibiotics and cardiovascular events by vaccination status during the influenza season. Methods We searched MEDLINE, EMBASE, CINAHL, Cochrane Library and considered any seasonal influenza vaccine, excluding the pandemic (2009–10 season) vaccine. Reviewers independently assessed data extraction and quality assessment. Results Of the 8308 citations retrieved, 22 studies were included in the systematic review. Overall, two studies (9%) were deemed at moderate risk of bias, thirteen (59%) at serious risk of bias and seven (32%) at critical risk of bias. For outpatient visits, we found modest evidence of protection by the influenza vaccine. For all-cause hospitalization outcomes, we found a wide range of results, mostly deemed at serious risk of bias. The included studies suggested that the vaccine may protect older adults against influenza hospitalizations and cardiovascular events. No article meeting our inclusion criteria explored the use of antibiotics and ILI hospitalizations. The high heterogeneity between studies hindered the aggregation of data into a meta-analysis. Conclusion The variability between studies prevented us from drawing a clear conclusion on the effectiveness of the influenza vaccine on healthcare utilization in older adults. Overall, the data suggests that the vaccine may result in a reduction of healthcare utilization in the older population. Further studies of higher quality are necessary.

Historically, Bartonella spp. have been associated with febrile illness (Oroya fever, trench fever, and cat scratch disease), endocarditis (numerous Bartonella spp.), and vasoproliferative lesions (Bartonella bacilliformis, Bartonella quintana, Bartonella henselae, and Bartonella vinsonii subsp. berkhoffii), occurring most often but not exclusively in immunocompromised patients. Recently, bloodstream infections with various Bartonella spp. have been documented in nonimmunocompromised individuals in association with a spectrum of cardiovascular, neurologic, and rheumatologic symptoms. As documented in this family, symptoms for which the medical implications remain unclear can occur in multiple family members infected with one or more Bartonella spp. Serial serologic and molecular microbiological findings supported exposure to or infection with Bartonella spp. in all seven family members. Either antibiotics failed to eliminate bacteremic infection, resulted in partial resolution of symptoms, or potentially reinfection occurred during the 19-month study period. There is a substantial need for clinical research to clarify the extent to which Bartonella spp. bacteremia induces nonspecific cardiovascular, neurologic, or rheumatologic symptoms, for ongoing improvement in the sensitivity and specificity of diagnostic testing, and clarification as to if, when, and how to treat patients with documented Bartonella spp. bacteremia.

Objective:BACTOT, Quebec’s healthcare-associated bloodstream infection (HABSI) surveillance program has been operating since 2007. In this study, we evaluated the changes in HABSI rates across 10 years of BACTOT surveillance under a Bayesian framework.Design:A retrospective, cohort study of eligible hospitals having participated in BACTOT for at least 3 years, regardless of their entry date. Multilevel Poisson regressions were fitted independently for cases of HABSI, catheter-associated bloodstream infections (CA-BSIs), non–catheter-associated primary BSIs (NCA-BSIs), and BSIs secondary to urinary tract infections (BSI-UTIs) as the outcome and log of patient days as the offset. The log of the mean Poisson rate was decomposed as the sum of a surveillance year effect, period effect, and hospital effect. The main estimate of interest was the cohort-level rate in years 2–10 of surveillance relative to year 1.Results:Overall, 17,479 cases and 33,029,870 patient days were recorded for the cohort of 77 hospitals. The pooled 10-year HABSI rate was 5.20 per 10,000 patient days (95% CI, 5.12–5.28). For HABSI, CA-BSI, and BSI-UTI, there was no difference between the estimated posterior rates of years 2–10 compared to year 1. The posterior means of the NCA-BSI rate ratios increased from the seventh year until the tenth year, when the rate was 29% (95% confidence interval, 1%–89%) higher than the first year rate.Conclusions:HABSI rates and those of the most frequent subtypes remained stable over the surveillance period. To achieve reductions in incidence, we recommend that more effort be expended in active interventions against HABSI alongside surveillance.

The filtration method (FM) is the most effective isolation technique for Epsilobacteriaceae from stool samples. FM’s different adaptations make it difficult to compare data between studies. This study was performed in three phases to optimize FM from a routine laboratory perspective. In July–September 2014 (part I), FM was performed on Mueller–Hinton agar containing 5% sheep blood and Columbia agar containing 5% sheep blood. In July 2016 (part II), FM was performed using 0.60-μm pore size polycarbonate filters (0.6-PC filter) and 0.45-μm pore size cellulose acetate filters (0.45-AC filter); in January 2018 (part III), the addition of hydrogen to incubators was studied. On 1146 stools analyzed in part I, the positive samples that showed no growth on the Butzler medium (n = 22/72, 30.6%) had improved growth of Epsilobacteriaceae when using the Columbia instead of the Mueller–Hinton medium (21/22 strains vs. 11/22, p

Vaccination has a huge public health impact. Maintaining vaccine coverage is key to avoid the devastating consequences of resurgence. In the Province of Quebec, vaccine coverage in young children are sub-optimal, mostly due to ambivalence toward vaccine safety and efficacy. We previously conducted a regional study in the Quebec’s Eastern Townships region, the PromoVac Study, to test a new educational intervention, based on motivational interviewing techniques, aimed at promoting infant vaccination. This first study evidenced that the intervention led to a marked increase in mothers’ intention to vaccinate, and vaccine coverage in their infants. The current study protocol aims at scaling up these results at a provincial level using a randomized controlled trial design. This pragmatic, randomized, controlled, parallel-group clinical trial will compare the effectiveness of the motivational interviewing to an educational intervention, including the distribution of an information flyer as standard of care on vaccination coverage in four maternity wards across the Province of Quebec (PromovaQ). Adult mothers of children born in participating maternity wards were recruited between March 2014 and February 2015. Vaccination coverage will be assessed at 3-years of age, thus the trial is expected to be completed in March 2019. Statistical analyses will be conducted under the intention-to-treat principle. Vaccine coverage will be analyzed using Chi-squared distribution testing and logistic regression to identify determinant factors. Secondary outcomes will include vaccine hesitation and intention scores, mother’s knowledge, attitudes and beliefs about immunization, and psychosocial determinants of intention to vaccinate. In the case results of this Provincial RCT be confirmed, serious consideration should then be given by Ministry of Health authorities to the possible implementation of MI-based strategies across provincial maternity wards. To ensure adequate input and secure implementation, study design and results will be reviewed with relevant stakeholders, including the children’s families, and provincial and regional decision-makers. Results will be adapted and shared with all stakeholders. ClinicalTrials.gov NCT02666872 (Retrospectively registered as January 28, 2016).

BACKGROUND: We documented inter-individual variability in the response to acute asthma therapy in children, attributed in part to five clinical factors (oxygen saturation, asthma severity score, virus detection, fever, symptoms between exacerbations; DOORWAY study). The contribution of genetic determinants of failure of acute asthma management have not been elucidated. OBJECTIVE: We aim to determine single nucleotide polymorphisms (SNP) associated with emergency department (ED) management failure in children. METHODS: A prospective cohort of 591 Caucasian children aged 1-17 years with moderate-to-severe asthma managed with standardized protocol were included. We examined 53 SNPs previously associated with asthma development, phenotypes, or bronchodilator or corticosteroids response. Associations between SNPs and management failure (hospitalization, active asthma management ≥8 h in ED, or a return visit within 72 h for one of two previous criteria) were examined using logistic regression, adjusting for the five clinical predictors of management failure. RESULTS: Four-hundred ninety-one subjects had complete clinical data and usable DNA samples. While controlling for clinical determinants, rs295137 in SPATS2L (OR = 1.77, 95%CI: 1.17, 2.68) was significantly associated with increased odds of ED management failure. Two SNPs in IL33 were associated with decreased odds of ED management failure: rs7037276 (OR = 0.55, 95%CI: 0.33, 0.90), and rs1342326 (OR = 0.52, 95%CI: 0.32, 0.86). The addition of these three SNPs to the clinical predictors significantly improved the model's predictive performance (P

Neuraminidase inhibitors (NAIs) are likely part of the rapid response and control in influenza pandemics and institutional outbreaks. We conducted a systematic review to appraise the current evidence on the use of NAIs among healthcare workers in the context of an influenza pandemic.

We performed viral culture of respiratory specimens in 118 severe acute respiratory coronavirus virus 2 (SARS-CoV-2)–infected healthcare workers (HCWs), ∼2 weeks after symptom onset. Only 1 HCW (0.8%) had a positive culture. No factors for prolonged viral shedding were identified. Infectivity is resolved in nearly all HCWs ∼2 weeks after symptom onset.

Introduction Mental health regional differences during pregnancy through the COVID-19 pandemic is understudied. Objectives We aimed to quantify the impact of the COVID-19 pandemic on maternal mental health during pregnancy. Methods A cohort study with a web-based recruitment strategy and electronic data collection was initiated in 06/2020. Although Canadian women, >18 years were primarily targeted, pregnant women worldwide were eligible. The current analysis includes data on women enrolled 06/2020-11/2020. Self-reported data included mental health measures (Edinburgh Perinatal Depression Scale (EPDS), Generalized Anxiety Disorders (GAD-7)), stress. We compared maternal mental health stratifying on country/continents of residence, and identified determinants of mental health using multivariable regression models. Results Of 2,109 pregnant women recruited, 1,932 were from Canada, 48 the United States (US), 73 Europe, 35 Africa, and 21 Asia/Oceania. Mean depressive symptom scores were lower in Canada (EPDS 8.2, SD 5.2) compared to the US (EPDS 10.5, SD 4.8) and Europe (EPDS 10.4, SD 6.5) (p Conclusions In this first international study on the impact of the COVID-19 pandemic, CONCEPTION has shown significant country/continent-specific variations in depressive symptoms during pregnancy, whereas severe anxiety was similar regardless of place of residence. Strategies are needed to reduce COVID-19’s mental health burden in pregnancy. Disclosure No significant relationships.

Objectives Correction factors have been proposed for traumatic lumbar punctures (LPs) in febrile young infants. However, no studies have assessed their diagnostic utility. We sought to determine the proportion of traumatic LPs safely reclassified as low risk for bacterial meningitis using recently derived white blood cell (WBC) and protein correction factors. Methods We retrospectively analyzed traumatic LPs among all febrile infants ≤60 days old at two tertiary paediatric hospitals from 2006 through 2018. Traumatic LPs were defined as ≥10,000 RBCs/mm3. Abnormal cerebrospinal fluid (CSF) WBCs and protein were adjusted downward using a newly derived correction factor (877 red blood cells [RBCs]: 1 WBC), three commonly used correction factors (500 WBCs: 1 RBC; 1,000 WBCs: 1 WBC; peripheral RBCs: WBCs), and a newly derived protein correction factor (1,000 RBCs: 0.011 g/L protein). Results There were 437 traumatic LPs including 357 (82%) with pleocytosis and 4 (0.9%) with bacterial meningitis. Overall, fewer infants were classified as having CSF pleocytosis using 877:1 and 1,000:1 ratios (38% and 43%, respectively), with 100% sensitivity and negative predictive value, and improved specificity (63% for 877:1, 58% for 1,000:1 ratios versus 19% for uncorrected counts). Among infants with pleocytosis, 877:1 and 1,000:1 ratios reclassified 191 (54%) and 171 (48%) as normal with no misclassified bacterial meningitis cases. Ratios of 500:1 and peripheral RBC:WBC misclassified 1 infant that had bacterial meningitis. Corrected CSF protein outperformed uncorrected protein in specificity but did not add diagnostic value following WBC-based correction. Conclusions Correction ratios of 877:1 and 1,000:1 safely reclassified half of all febrile infants ≤60 days. These corrections should be considered when interpreting CSF results of traumatic LPs.

Background Medications already available to treat other conditions are presently being studied in clinical trials as potential treatments for COVID-19. Given that pregnant women are excluded from these trials, we aimed to investigate their safety when used during pregnancy within a unique population source. Methods Using the population-based Quebec Pregnancy Cohort, we identified women who delivered a singleton liveborn (1998–2015). Taking potential confounders into account including indications for use, the risk of prematurity, low birth weight (LBW), small for gestational age (SGA), and major congenital malformation (MCM) associated with COVID-19 repurposed drug use during pregnancy were quantified using generalized estimation equations. Results Of the 231,075 eligible pregnancies, 107 were exposed to dexamethasone (0.05%), 31 to interferons (0.01%), 1,398 to heparins (0.60%), 24 to angiotensin-receptor blockers (ARB) (0.01%), 182 to chloroquine (0.08%), 103 to hydroxychloroquine (0.05%), 6,206 to azithromycin (2.70%), 230 to oseltamivir (0.10%), and 114 to HIV medications (0.05%). Adjusting for potential confounders, we observed an increased risk of prematurity related to dexamethasone (aOR 1.92, 95%CI 1.11–3.33; 15 exposed cases), anti-thrombotics (aOR 1.58, 95%CI 1.31–1.91; 177 exposed cases), and HIV medications (aOR 2.04, 95%CI 1.01–4.11; 20 exposed cases) use. An increased risk for LBW associated with anti-thrombotics (aOR 1.72, 95%CI 1.41–2.11; 152 exposed cases), and HIV medications (aOR 2.48, 95%CI 1.25–4.90; 21 exposed cases) use were also found. Gestational exposure to anti-thrombotics (aOR 1.20, 95%CI 1.00–1.44; 176 exposed cases), and HIV medications (aOR 2.61, 95%CI 1.51–4.51; 30 exposed cases) were associated with SGA. First-trimester dexamethasone (aOR 1.66, 95%CI 1.02–2.69; 20 exposed cases) and azithromycin (aOR 1.10, 95%CI 1.02–1.19; 747 exposed cases) exposures were associated with MCM. Conclusions Many available medications considered as treatments for COVID-19 are associated with adverse pregnancy outcomes. Caution is warranted when considering these medications during the gestational period.

POINTS CLES Le 11 mars 2020[1][1], les taux alarmants de propagation du coronavirus du syndrome respiratoire aigu severe 2 (SRAS-CoV-2) ont pousse l’Organisation mondiale de la sante (OMS) a declarer l’etat de pandemie concernant la nouvelle maladie a coronavirus 2019 (COVID-19). La

KEY POINTS Alarming levels of spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) triggered the World Health Organization (WHO) to declare novel coronavirus disease 2019 (COVID-19) a pandemic on Mar. 11, 2020.[1][1] The pandemic is ongoing and has caused substantial morbidity and

Objectives We hypothesized that antibiotic use in PICUs is based on criteria not always supported by evidence. We aimed to describe determinants of empiric antibiotic use in PICUs in eight different countries. Design Cross-sectional survey. Setting PICUs in Canada, the United States, France, Italy, Saudi Arabia, Japan, Thailand, and Brazil. Subjects Pediatric intensivists. Interventions None. Measurements and main results We used literature review and focus groups to develop the survey and its clinical scenarios (pneumonia, septic shock, meningitis, and intra-abdominal infections) in which cultures were unreliable due to antibiotic pretreatment. Data analyses included descriptive statistics and linear regression with bootstrapped SEs. Overall response rate was 39% (482/1,251), with individual country response rates ranging from 25% to 76%. Respondents in all countries prolonged antibiotic duration based on patient characteristics, disease severity, pathogens, and radiologic findings (from a median increase of 1.8 d [95% CI, 0.5-4.0 d] to 9.5 d [95% CI, 8.5-10.5 d]). Younger age, severe disease, and ventilator-associated pneumonia prolonged antibiotic treatment duration despite a lack of evidence for such practices. No variables were reported to shorten treatment duration for all countries. Importantly, more than 39% of respondents would use greater than or equal to 7 days of antibiotics for patients with a positive viral polymerase chain reaction test in all scenarios, except in France for pneumonia (29%), septic shock (13%), and meningitis (6%). The use of elevated levels of inflammatory markers to prolong antibiotic treatment duration varied among different countries. Conclusions Antibiotic-related decisions are complex and may be influenced by cultural and contextual factors. Evidence-based criteria are necessary to guide antibiotic duration and ensure the rational use of antibiotics in PICUs.

Highlights • Practical, evidence-informed advice considers the spectrum of public health science. • This framework fills a gap in the comprehensive development of vaccine guidance. • It enables the systematic examination of ethics, equity, feasibility, and acceptability. • In Canada, successful implementation has led to timely, transparent recommendations. • These tools, based on extensive research, can be used by advisory groups worldwide., For the successful implementation of population-level recommendations, it is critical to consider the full spectrum of public health science, including clinical and programmatic factors. Current frameworks may identify various factors that should be examined when making evidence-informed vaccine-related recommendations. However, while most immunization guidelines systematically assess clinical factors, such as efficacy and safety of vaccines, there is no published framework outlining how to systematically assess programmatic factors, such as the ethics, equity, feasibility, and acceptability of recommendations. We have addressed this gap with the development of the EEFA (Ethics, Equity Feasibility, Acceptability) Framework, supported by evidence-informed tools, including Ethics Integrated Filters, Equity Matrix, Feasibility Matrix, and an Acceptability Matrix. The Framework and tools are based on five years of environmental scans, systematic reviews and surveys, and refined by expert and stakeholder consultations and feedback. For each programmatic factor, the EEFA Framework summarizes the minimum threshold for consideration and when further in-depth analysis may be required, which aspects of the factor should be considered, how to assess the factor using the supporting evidence-informed tools, and who should be consulted to complete the assessment. Research, particularly in the fields of vaccine acceptability and equity, has validated the utility and comprehensiveness of the tools. The Framework has been successfully used in Canada for clear, timely, transparent vaccine guidance with positive stakeholder feedback on its comprehensiveness, relevance and appropriateness. Applying the EEFA Framework allows for the systematic consideration of the spectrum of public health science without a delay in recommendations, complementing existing decision-making frameworks. This Framework will therefore be useful for advisory groups worldwide to integrate critical factors that could impact the successful and timely implementation of comprehensive, transparent recommendations, and will further the global objective of developing practical and evidence-informed immunization policies.

Diagnostic testing to identify persons infected with severe acute respiratory syndrome–related coronavirus-2 (SARS–CoV-2) infection is central to control the global pandemic of COVID-19 that began in late 2019. In a few countries, the use of diagnostic testing on a massive scale has been a cornerstone of successful containment strategies. In contrast, the United States, hampered by limited testing capacity, has prioritized testing for specific groups of persons. Real-time reverse transcriptase polymerase chain reaction–based assays performed in a laboratory on respiratory specimens are the reference standard for COVID-19 diagnostics. However, point-of-care technologies and serologic immunoassays are rapidly emerging. Although excellent tools exist for the diagnosis of symptomatic patients in well-equipped laboratories, important gaps remain in screening asymptomatic persons in the incubation phase, as well as in the accurate determination of live viral shedding during convalescence to inform decisions to end isolation. Many affluent countries have encountered challenges in test delivery and specimen collection that have inhibited rapid increases in testing capacity. These challenges may be even greater in low-resource settings. Urgent clinical and public health needs currently drive an unprecedented global effort to increase testing capacity for SARS–CoV-2 infection. Here, the authors review the current array of tests for SARS–CoV-2, highlight gaps in current diagnostic capacity, and propose potential solutions., Diagnostic testing to identify infected persons is central to efforts to control the COVID-19 pandemic. This review synthesizes current knowledge of diagnostic options available to clinicians, highlights key gaps in current diagnostic capacity, and discusses potential solutions.