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Invasive pneumococcal disease due to Streptococcus pneumoniae can cause mortality and severe morbidity due to sepsis, meningitis and pneumonia, particularly in young children and the elderly. Recurrent invasive pneumococcal disease is rare yet serious sequelae of invasive pneumococcal disease that is associated with the immunocompromised and leads to a high mortality rate.This retrospective study reviewed recurrent invasive pneumococcal disease cases from the Canadian Immunization Monitoring Program, ACTive (IMPACT) between 1991 and 2019, an active network for surveillance of vaccine-preventable diseases and adverse events following immunization for children ages 0-16 years. Data were collected from 12 pediatric tertiary care hospitals across all 3 eras of public pneumococcal conjugate vaccine implementation in Canada.The survival rate within our cohort of 180 recurrent invasive pneumococcal disease cases was 98.3%. A decrease of 26.4% in recurrent invasive pneumococcal disease due to vaccine serotypes was observed with pneumococcal vaccine introduction. There was also a 69.0% increase in the rate of vaccination in children with preexisting medical conditions compared with their healthy peers.The decrease in recurrent invasive pneumococcal disease due to vaccine-covered serotypes has been offset by an increase of non-vaccine serotypes in this sample of Canadian children.

After the introduction of pneumococcal conjugate vaccines for children, invasive pneumococcal disease caused by Streptococcus pneumoniae serotype 4 declined in all ages in Alberta, Canada, but it has reemerged and spread in adults in Calgary, primarily among persons who are experiencing homelessness or who use illicit drugs. We conducted clinical and molecular analyses to examine the cases and isolates. Whole-genome sequencing analysis indicated relatively high genetic variability of serotype 4 isolates. Phylogenetic analysis identified 1 emergent sequence type (ST) 244 lineage primarily associated within Alberta and nationally distributed clades ST205 and ST695. Isolates from 6 subclades of the ST244 lineage clustered regionally, temporally, and by homeless status. In multivariable logistic regression, factors associated with serotype 4 invasive pneumococcal disease were being male, being

Adults previously infected with SARS-CoV-2 develop short-term immunity and may have increased reactogenicity to COVID-19 vaccines. This prospective, multi-center active surveillance cohort study examined the short-term safety of COVID-19 vaccines in adults with a prior history of SARS-CoV-2.Canadian adults vaccinated between December 22, 2020 and November 27, 2021 were sent an electronic questionnaire 7 days post dose 1, dose 2 and dose 3 vaccination. The main outcome was health events occurring in the first 7 days after each vaccination that prevented daily activities, resulted in work absenteeism or required a medical consultation, including hospitalization.Among 684,998 vaccinated individuals, 2.6% (18,127/684,998) reported a prior history of SARS-CoV-2 infection a median of 4 months (interquartile range 2-6 months) previously. After dose 1, individuals with moderate (bedridden) to severe (hospitalized) COVID-19 who received BNT162b2, mRNA1273 or ChAdox1-S vaccines had higher odds of a health event preventing daily activities, resulting in work absenteeism or requiring medical consultation; adjusted odds ratio (AOR) 3.96 (95% CI 3.67-4.28) for BNT162b2, 5.01 (4.57-5.50) for mRNA1273 and 1.84 (1.54-2.20) for ChAdox1-S compared to no infection. Following dose 2 and 3, the greater risk associated with previous infection was also present but attenuated compared to dose 1. For all doses, the association was lower or absent after mild or asymptomatic infection.Adults with moderate or severe previous SARS-CoV-2 infection were more likely to have a health event sufficient to impact routine activities or require medical assessment in the week following each vaccine doses.

Background: Transplacentally transferred antibodies induced by maternal pertussis vaccination interfere with infant immune responses to pertussis primary vaccination. We evaluated whether this interference remains in toddlers after booster vaccination. Methods: In a prior phase IV, observer-blind, placebo-controlled, randomized study (NCT02377349), pregnant women in Australia, Canada and Europe received intramuscular tetanus-reduced-antigen-content diphtheria-three-component acellular pertussis vaccine (Tdap group) or placebo (control group) at 270/7–366/7 weeks’ gestation, with crossover immunization postpartum. Their infants were primed (study NCT02422264) and boosted (at 11–18 months; current study NCT02853929) with diphtheria-tetanus-three-component acellular pertussis-hepatitis B virus-inactivated poliovirus/Haemophilus influenzae type b vaccine (DTaP-HepB-IPV/Hib) and 13-valent pneumococcal conjugate vaccine. Immunogenicity before and after booster vaccination, and reactogenicity and safety of the booster were evaluated descriptively. Results: 263 (Tdap group) and 277 (control group) toddlers received a DTaP-HepB-IPV/Hib booster. Pre-booster vaccination, observed geometric mean concentrations (GMCs) for the three pertussis antigens and diphtheria were 1.4–1.5-fold higher in controls than in the Tdap group. No differences were observed for the other DTaP-HepB-IPV/Hib antigens. One month post-booster vaccination, booster response rates for pertussis antigens were ≥ 92.1% and seroprotection rates for the other DTaP-HepB-IPV/Hib antigens were ≥ 99.2% in both groups (primary objective). Higher post-booster GMCs were observed in controls versus the Tdap group for anti-filamentous hemagglutinin (1.2-fold), anti-pertussis toxoid (1.5-fold) and anti-diphtheria (1.4-fold). GMCs for the other DTaP-HepB-IPV/Hib antigens were similar between groups. Serious adverse events were reported for three toddlers (controls, not vaccination-related). One death occurred pre-booster (Tdap group, not vaccination-related). Conclusions: As a consequence of interference of maternal pertussis antibodies with infant immune responses to pertussis primary vaccination, pertussis antibody concentrations were still lower in toddlers from Tdap-vaccinated mothers before DTaP-HepB-IPV/Hib booster vaccination. After the booster, antibody concentrations were lower for filamentous hemagglutinin and pertussis toxoid but not for pertactin. The clinical significance of this interference requires further evaluation. Clinical Trial Registration. ClinicalTrials.gov: NCT02853929. publishedVersion

Background Norovirus is a leading cause of acute gastroenteritis. With vaccines in development, population-based estimates of norovirus burden are needed to identify target populations, quantify potential benefits, and understand disease dynamics. Methods We estimated the attributable fraction (AF) for norovirus infections in children, defined as the proportion of children testing positive for norovirus whose gastroenteritis was attributable to norovirus. We calculated the standardized incidence and emergency department (ED) visit rates attributable to norovirus using provincial gastroenteritis visit administrative data. Results From 3731 gastroenteritis case patients and 2135 controls we determined that the AFs were 67.0% (95% confidence interval [CI], 31.5%–100%) and 91.6% (88.8%–94.4%) for norovirus genogroups I (GI) and II (GII), respectively. Norovirus GII AF varied by season but not age. We attributed 116 episodes (95% CI, 103–129) and 59 (51–67) ED visits per 10 000 child-years to norovirus GII across all ages, accounting for 20% and 18% of all medically attended gastroenteritis episodes and ED visits, respectively. Conclusions In children, a large proportion of norovirus GII detections reflect causation, demonstrating significant potential for norovirus GII vaccines. Seasonal variation in the norovirus GII AF may have implications for understanding the role asymptomatic carriage plays in disease dynamics.

Pregnant individuals have been receiving COVID-19 vaccines following pre-authorisation clinical trials in non-pregnant people. This study aimed to determine the frequency and nature of significant health events among pregnant females after COVID-19 vaccination, compared with unvaccinated pregnant controls and vaccinated non-pregnant individuals.We did an observational cohort study, set in seven Canadian provinces and territories including Ontario, Quebec, British Columbia, Alberta, Nova Scotia, Yukon, and Prince Edward Island. Eligibility criteria for vaccinated individuals were a first dose of a COVID-19 vaccine within the previous 7 days; an active email address and telephone number; ability to communicate in English or French; and residence in the aforementioned provinces or territories. Study participants were pregnant and non-pregnant females aged 15-49 years. Individuals were able to participate as controls if they were unvaccinated and fulfilled the other criteria. Data were collected primarily by self-reported survey after both vaccine doses, with telephone follow-up for those reporting any medically attended event. Participants reported significant health events (new or worsening of a health event sufficient to cause work or school absenteeism, medical consultation, or prevent daily activities) occurring within 7 days of vaccination or within the past 7 days for unvaccinated individuals. We employed multivariable logistic regression to examine significant health events associated with mRNA vaccines, adjusting for age group, previous SARS-CoV-2 infection, and trimester, as appropriate.As of Nov 4, 2021, 191 360 women aged 15-49 years with known pregnancy status had completed the first vaccine dose survey and 94 937 had completed the second dose survey. 180 388 received one dose and 94 262 received a second dose of an mRNA vaccine, with 5597 pregnant participants receiving dose one and 3108 receiving dose two, and 174 765 non-pregnant participants receiving dose one and 91 131 receiving dose two. Of 6179 included unvaccinated control participants, 339 were pregnant and 5840 were not pregnant. Overall, 226 (4·0%) of 5597 vaccinated pregnant females reported a significant health event after dose one of an mRNA vaccine, and 227 (7·3%) of 3108 after dose two, compared with 11 (3·2%) of 339 pregnant unvaccinated females. Pregnant vaccinated females had an increased odds of a significant health event within 7 days of the vaccine after dose two of mRNA-1273 (adjusted odds ratio [aOR] 4·4 [95% CI 2·4-8·3]) compared with pregnant unvaccinated controls within the past 7 days, but not after dose one of mRNA-1273 or any dose of BNT162b2. Pregnant vaccinated females had decreased odds of a significant health event compared with non-pregnant vaccinated females after both dose one (aOR 0·63 [95% CI 0·55-0·72]) and dose two (aOR 0·62 [0·54-0·71]) of any mRNA vaccination. There were no significant differences in any analyses when restricted to events which led to medical attention.COVID-19 mRNA vaccines have a good safety profile in pregnancy. These data can be used to appropriately inform pregnant people regarding reactogenicity of COVID-19 vaccines during pregnancy, and should be considered alongside effectiveness and immunogenicity data to make appropriate recommendations about best use of COVID-19 vaccines in pregnancy.Canadian Institutes of Health Research, Public Health Agency of Canada.

IntroductionCOVID-19 vaccines require enhanced safety monitoring after emergency approval. The Canadian National Vaccine Safety Network monitors the safety of COVID-19 vaccines and provides enhanced monitoring for healthy, auto-immune, immunocompromised, pregnant and breastfeeding populations and allows for the detection of safety signals.Methods and analysisOnline participant reporting of health events in vaccinated and unvaccinated individuals 12 years of age and older is captured in three surveys: 1 week after dose 1, 1 week after dose 2 and 7 months after dose 1. Medically attended events are followed up by telephone. The number, percentage, rate per 10 000 and incident rate ratios with 95% CIs are calculated by health event, vaccine type, sex and in 10-year age groups.Ethics and disseminationEach study site has Research Ethics Board approvals for the project (UBC Children’s & Women’s, CIUSSS de l'Estrie—CHUS, Health PEI, Conjoint Health Research Ethics Board, University of Calgary and Alberta Health Services, IWK Health, Unity Health Toronto and CHU de Québec-Université Laval Research Ethics Boards). Individuals are invited to participate in this active surveillance and electronic consent is given before proceeding to each survey. Weekly reports are shared with public health and posted on the study website. At least one peer-reviewed manuscript is produced.

Although the passage of blood in stools in children represents a medical emergency, children seeking emergency department (ED) care remain poorly characterized. Our primary objective was to compare clinical characteristics and etiologic pathogens in children with acute diarrhea with and without caregiver-reported hematochezia. Secondary objectives were to characterize interventions and resource utilization.We conducted a secondary analysis of the Alberta Provincial Pediatric EnTeric Infection TEam (APPETITE) database. Children18 years presenting to two pediatric EDs within a 24-hour period and7 days of symptoms were consecutively recruited.Of 1,061 participants, 115 (10.8%) reported hematochezia at the enrollment visit at which time those with hematochezia, compared to those without, had more diarrheal episodes/24-hour period (9 vs. 6; difference: 2; 95% confidence interval [CI]: 2.0, 4.0; p 0.001), and were less likely to have experienced vomiting (54.8% vs. 80.2%; difference: -25.4; 95% CI: -34.9, -16.0; p 0.001). They were more likely to receive intravenous fluids (33.0% vs. 17.9%; difference: 15.2; 95% CI: 6.2, 24.1; p 0.001) and require repeat health care visits (45.5% vs. 34.7%; difference: 10.7; 95% CI: 0.9, 20.6; p = 0.03). A bacterial pathogen was identified in 33.0% of children with hematochezia versus 7.9% without (difference: 25.1; 95% CI: 16.3, 33.9; p 0.001); viruses were detected in 31.3% of children with hematochezia compared to 72.3% in those without (difference: -41.0%, 95% CI: -49.9, -32.1; p 0.001).In children with acute diarrhea, caregiver report of hematochezia, compared to the absence of hematochezia, was associated with more diarrheal but fewer vomiting episodes, and greater resource consumption. The former group of children was also more likely to have bacteria detected in their stool.

Primary Subject area Emergency Medicine - Paediatric Background Many children with acute gastroenteritis (AGE) experience moderate-to-severe pain. To date, the relationship between specific enteropathogens and pain intensity in children with AGE is poorly characterized. Objectives To describe pain severity experienced by children with AGE, by enteropathogen type (i.e., bacteria, virus, co-detection) during the 24 hours prior to emergency department (ED) presentation and while in the ED. We also sought to describe analgesic medication use in AGE. Design/Methods Children 0 to under 18 years with symptoms of AGE (vomiting and/or diarrhea, less than 7 days duration) were prospectively recruited in two pediatric EDs from December 2014 to August 2018. Rectal swabs and stool specimens were analyzed with a commercial enteric panel, an in-house viral panel, and standard enteric bacterial culture. Pain severity was reported by caregivers, with input from the child whenever possible, using a validated 11-point Verbal Numerical Rating Scale from 0 (no pain) to 10 (maximum pain). Results 2686 children with AGE participated in the study. The overall maximal mean pain score was 5.50 (SD 3.00) during the 24 hours preceding the ED visit. Children with bacteria detected in their stool had a significantly higher mean pain score (difference: 1.10 [95% CI: 0.36, 1.84]) prior to ED visit and 1.32 (95% CI: 0.54, 2.10) while in the ED, compared to those with no pathogen identified. They also had significantly higher mean pain scores (difference: 1.10 [95%CI: 0.39, 1.81]) prior to ED visit and 1.44 (95%CI: 0.69, 2.20) while in the ED when compared to AGE caused by a single virus. Using a multivariable regression model, the association between pain severity and enteropathogen type was no longer demonstrated; however, longer illness duration (p=0.01), fever (p < 0.0001), increased number of diarrheal (p < 0.0001) and vomiting (p=0.03) episodes, and respiratory symptoms (p=0.03) were all associated with greater pain at home. Overall, analgesic use was low, with 41.6% (1117/2686) and 20.0% (538/2686) of participants receiving an analgesic at home and in the ED, respectively. Conclusion Enteropathogen type was not predictive of greater pain severity after adjustment for clinical symptoms (i.e., vomiting and diarrhea). The clinical constellation of symptoms accompanying any particular pathogen may differ between pathogens, and this clinical picture may play the greater role in pain experience. Analgesic use was low in children with this painful condition.

Background and Aims The effectiveness and safety of vaccinations can be altered by immunosuppressive therapies, and perhaps by inflammatory bowel disease (IBD) itself. These recommendations developed by the Canadian Association of Gastroenterology and endorsed by the American Gastroenterological Association, aim to provide guidance on immunizations in adult and pediatric patients with IBD. This publication focused on inactivated vaccines. Methods Systematic reviews evaluating the efficacy, effectiveness, and safety of vaccines in patients with IBD, other immune-mediated inflammatory diseases, and the general population were performed. Critical outcomes included mortality, vaccine-preventable diseases, and serious adverse events. Immunogenicity was considered a surrogate outcome for vaccine efficacy. Certainty of evidence and strength of recommendations were rated according to the GRADE (Grading of Recommendation Assessment, Development, and Evaluation) approach. Key questions were developed through an iterative online platform, and voted on by a multidisciplinary group. Recommendations were formulated using the Evidence-to-Decision framework. Strong recommendation means that most patients should receive the recommended course of action, whereas a conditional recommendation means that different choices will be appropriate for different patients. Results Consensus was reached on 15 of 20 questions. Recommendations address the following vaccines: Haemophilus influenzae type b, recombinant zoster, hepatitis B, influenza, pneumococcus, meningococcus, tetanus-diphtheria-pertussis, and human papillomavirus. Most of the recommendations for patients with IBD are congruent with the current Centers for Disease Control and Prevention and Canada’s National Advisory Committee on Immunization recommendations for the general population, with the following exceptions. In patients with IBD, the panel suggested Haemophilus influenzae type b vaccine for patients older than 5 years of age, recombinant zoster vaccine for adults younger than 50 year of age, and hepatitis B vaccine for adults without a risk factor. Consensus was not reached, and recommendations were not made for 5 statements, due largely to lack of evidence, including double-dose hepatitis B vaccine, timing of influenza immunization in patients on biologics, pneumococcal and meningococcal vaccines in adult patients without risk factors, and human papillomavirus vaccine in patients aged 27–45 years. Conclusions Patients with IBD may be at increased risk of some vaccine-preventable diseases. Therefore, maintaining appropriate vaccination status in these patients is critical to optimize patient outcomes. In general, IBD is not a contraindication to the use of inactivated vaccines, but immunosuppressive therapy may reduce vaccine responses.

Background Data on the serologic status of childhood vaccines, cytomegalovirus (CMV) and Epstein-Barr virus (EBV), are limited in inflammatory bowel disease (IBD). Therefore, we evaluated vaccine coverage and seroprotection, along with CMV and EBV seropositivity, in pediatric IBD. Methods In a cross-sectional study, demographic data, IBD history, vaccine records, and serum for antibodies against measles, mumps, rubella, diphtheria, tetanus, varicella, hepatitis B (HBV), CMV, and EBV were collected from children with IBD. We evaluated potential factors associated with serologic status. Results Of 156 subjects, vaccine coverage was up to date for age in 93.5% for measles, mumps, rubella, 95.6% for diphtheria, tetanus, pertussis, polio, hemophilus influenza B, 75.8% for HBV, and 93.5% for varicella, including past infection and vaccination. Seroprotection was present in 65.8% for measles, 60.5% for mumps, 79.1% for rubella, 79.5% for diphtheria, 80.8% for tetanus, 70.5% for varicella, and 62.8% for HBV of subjects. Older age at diagnosis was associated with seroprotection among subjects with complete HBV (odds ratio [OR], 1.20; 95% confidence interval [CI], 1.03-1.39) and rubella series (OR, 1.18; 95% CI, 1.02-1.37). Older age at serum collection was associated with seroprotection among subjects with prior varicella vaccination or infection (OR, 1.69; 95% CI, 1.33-2.15). Only 25.2% and 37.8% demonstrated seropositivity to CMV and EBV, respectively. Among subjects on immunosuppressive medications, 75.3% and 62.4% were seronegative for CMV and EBV, respectively. Conclusions Children with IBD have low serologic protection to childhood vaccines in spite of high vaccine coverage and universal vaccinations. Children with IBD, including a large proportion on immunosuppressive medications, have low seropositivity to CMV and EBV.

Background Recent increases in pertussis morbidity and mortality rates among young infants have led to a recommendation in some countries for vaccination against pertussis during pregnancy. Having data on the burden of pediatric pertussis in a large population over time is important for establishing the true burden of disease in the acellular pertussis (aP) vaccine era. Here, we describe age-specific epidemiology and morbidity and mortality rates in children hospitalized with pertussis over 17 years across Canada in the aP vaccine era. Methods Patients aged ≤16 years who were admitted to 1 of 12 pediatric tertiary-care hospitals across Canada between 1999 and 2015 with confirmed (laboratory-confirmed or epidemiologically linked) or probable (clinically diagnosed) pertussis were included. Results Overall, 1402 patients with pertussis were included. Infants aged, Infants aged

Background Bacterial meningitis is a severe infection of the nervous system with a high complication rate including stroke. The purpose of this study is to assess the incidence, risk factors, patterns, and outcomes in pediatric meningitis complicated by stroke. Methods The study design was a population-based, 10-year retrospective (2002 to 2012) cohort study set in Southern Alberta, Canada. The inclusion criteria were: (1) age from newborn to 18 years, (2) brain magnetic resonance imaging (MRI) including diffusion-weighted imaging during admission, and (3) laboratory confirmed acute bacterial meningitis. The main outcomes were demographics, clinical presentations, risk factors, laboratory findings, radiographic findings, and neurological outcomes. Findings Forty-three patients had confirmed bacterial meningitis and diffusion MRI (9 neonates (21%), 89% male; 22 infants aged one month to one year (51%), 50% male; and 12 children older than one year (28%), 58% male, median age four years (interquartile range 7.9 years). Ischemic stroke was confirmed in 16/43 (37%), often multifocal (94%). Patients with stroke were significantly more likely to have seizures (P = 0.025), otitis media (P = 0.029), and multiple presentations to hospital (P = 0.013). Mortality was 25% in children with stroke compared with 4% in those without (P = 0.067). Survivors with stroke were more likely to have neurological deficits at follow-up (69% versus 26%, P = 0.019). Conclusions More than one-third of children with acute bacterial meningitis and clinically indicated MRI had ischemic stroke. Stroke was associated with clinical factors including duration of illness, seizures, and causative organisms. Stroke was associated with higher mortality and morbidity, warranting consideration of increased MRI screening and new approaches to treatment.

The objective of this study was to characterize the etiological role of human adenovirus (HAdV) serotypes in pediatric gastroenteritis. Using a case-control design, we compared the frequencies of HAdV serotypes between children with ≥3 episodes of vomiting or diarrhea within 24 h and

Background & AimsPatients with inflammatory bowel disease (IBD) may be at increased risk of some vaccine-preventable diseases. The effectiveness and safety of vaccinations may be altered by immunosuppressive therapies or IBD itself. These recommendations, developed by the Canadian Association of Gastroenterology and endorsed by the American Gastroenterological Association, aim to provide guidance on immunizations in patients with inflammatory bowel disease. This publication focused on live vaccines.MethodsSystematic reviews evaluating the efficacy, effectiveness, and safety of vaccines in patients with IBD, other immune-mediated inflammatory diseases, and the general population were performed. Critical outcomes included mortality, vaccine-preventable diseases, and serious adverse events. Immunogenicity was considered a surrogate outcome for vaccine efficacy. Certainty of evidence and strength of recommendations were rated according to the GRADE (Grading of Recommendation Assessment, Development, and Evaluation) approach. Key questions were developed through an iterative process and voted on by a multidisciplinary panel. Recommendations were formulated using the Evidence-to-Decision framework. Strong recommendation means that most patients should receive the recommended course of action, whereas a conditional recommendation means that different choices will be appropriate for different patients.ResultsThree good practice statements included reviewing a patient’s vaccination status at diagnosis and at regular intervals, giving appropriate vaccinations as soon as possible, and not delaying urgently needed immunosuppressive therapy to provide vaccinations. There are 4 recommendations on the use of live vaccines. Measles, mumps, rubella vaccine is recommended for both adult and pediatric patients with IBD not on immunosuppressive therapy, but not for those using immunosuppressive medications (conditional). Varicella vaccine is recommended for pediatric patients with IBD not on immunosuppressive therapy, but not for those using immunosuppressive medications (conditional). For adults, recommendations are conditionally in favor of varicella vaccine for those not on immunosuppressive therapy, and against for those on therapy. No recommendation was made regarding the use of live vaccines in infants born to mothers using biologics because the desirable and undesirable effects were closely balanced and the evidence was insufficient.ConclusionsMaintaining appropriate vaccination status in patients with IBD is critical to optimize patient outcomes. In general, live vaccines are recommended in patients not on immunosuppressive therapy, but not for those using immunosuppressive medications. Additional studies are needed to evaluate the safety and efficacy of live vaccines in patients on immunosuppressive therapy.

OBJECTIVES: To determine if the clinical characteristics of children with gastroenteritis and influenza identified in their stool differ from those whose stool was influenza-negative. METHODS: Children

Background The Canadian National Vaccine Safety (CANVAS) network monitors the safety of seasonal influenza vaccines in Canada. Aim To provide enhanced surveillance for seasonal influenza and pandemic influenza vaccines. Methods In 2017/18 and 2018/19 influenza seasons, adults (≥ 15 years of age) and parents of children vaccinated with the seasonal influenza vaccine participated in an observational study using web-based active surveillance. Participants completed an online survey for health events occurring in the first 7 days after vaccination. Participants who received the influenza vaccine in the previous season, but had not yet been vaccinated for the current season, were unvaccinated controls. Results In 2017/18, 43,751 participants and in 2018/19, 47,798 completed the online safety survey. In total, 957 of 30,173 participants vaccinated in 2017/18 (3.2%; 95% confidence interval (CI): 3.0–3.4) and 857 of 25,799 participants vaccinated in 2018/19 (3.3%; 95% CI: 3.1–3.5) reported a health problem of sufficient intensity to prevent their normal daily activities and/or cause them to seek medical care (including hospitalisation). This compared to 323 of 13,578 (2.4%; 95% CI: 2.1–2.6) and 544 of 21,999 (2.5%; 95% CI: 2.3–2.7) controls in each respective season. The event rate in vaccinated adults and children was higher than the background rate and was associated with specific influenza vaccines. The higher rate of events was associated with systemic symptoms and migraines/headaches. Conclusion In 2017/18 and 2018/19, higher rates of events were reported following seasonal influenza vaccination than in the pre-vaccination period. This signal was associated with several seasonal influenza vaccine products.

During the 2009 H1N1 pandemic, individuals with obesity were disproportionately affected by H1N1 with increased levels of mortality and morbidity. This led to questions regarding the potential impact of lifestyle on the effectiveness of immunization. Currently, the research is limited on influenza vaccination and the associated changes in immune response with body composition and physical activity. The purpose of this pilot study was to investigate the potential role of adiposity and physical activity in the immune response elicited by the 2014/2015 seasonal trivalent influenza vaccine. A prospective cohort study examining the 2014/2015 seasonal trivalent influenza vaccine was conducted by collecting baseline and 4-week postvaccination fasting blood samples from 45 male Albertans between the ages of 18 and 35 years. Percent body fat (%BF) was assessed through dual X-ray absorptiometry imagining and physical activity through self-reported survey scores. While no differences in median %BF were associated with seroconversion rates in participants, the median physical activity score was higher among those that did not seroconvert to the vaccine. Significant differences were found for the A/Texas strain (p < 0.01) and a similar trend of lower magnitude observed for the remaining 2 influenza strains. These results suggest that higher physical activity levels may influence immune response to vaccination and that assessing factors beyond those commonly used can be of value when identifying vaccine response in the population.

Background There is mounting evidence that the recent resurgence of pertussis in many countries is in part related to the acellular vaccine, which has been administered in Canada since 1997. This vaccine elicits a different cell-mediated immune response than the previously used whole-cell vaccine, and its effectiveness wanes over time. The aim of this study is to understand the immunological, demographic and clinical factors that mediate protection from pertussis on exposure. Methods This is a household case-control study protocol. Following notification of an index case in a household, a study team will conduct a home visit to collect data and biological specimens. The study team will return to the household 8 weeks from the onset of illness in the index case. The Th1, Th2 and Th17 responses, cytokine expression, IgG subclass, blood cell counts and presence of Bordetella pertussis will be determined. We will use laboratory and statistical analyses to determine immunological differences between contacts who are infected with B. pertussis and contacts who remain healthy, and to determine which clinical and demographic covariates are associated with a reduced risk of infection. Interpretation The results of this study will be essential for understanding the immune response required for protection from infection with B. pertussis and will contribute to our understanding of the shortcomings of the current vaccine.

BACKGROUND A previous study in Calgary showed that travel to India was associated with high risk of community-onset infections with extended-spectrum β-lactamase (ESBL)-producing Escherichia coli. We performed a follow-up study to determine the rate of rectal acquisition of ESBL-producing E. coli among travellers to South Asia and to identify the behaviours putting such travellers at high risk for acquiring ESBL-producing E. coli. METHODS: The study was performed at a travel clinic in Calgary. Travellers 18 years or older who were planning to visit South Asia for a period of at least 5 days were included. Three rectal swabs were obtained, and 2 questionaires were administered (before and after travel). RESULTS A total of 149 travellers participated between January 2012 and July 2014; of these, 116 (78%) provided rectal swabs upon return to Calgary and completed both pre- and post-travel questionaires. Of the 109 travellers without colonization with ESBL-producing E. coli upon enrollment, 70 (64%) acquired ESBL-producing E. coli during travel. Of the 90 participants who visited India, 66 (73%) were positive for ESBL-producing E. coli upon their return to Calgary. Most ESBL-producing E. coli specimens were identified as producing the enzyme CTX-M-15. Behaviours associated with a statistically significant risk of acquiring ESBL-producing E. coli included visiting India (odds ratio [OR] 19.9, 95% confidence interval [CI] 4.5-88.8), consuming meals with the local population (OR 6.9, 95% CI 1.2-39.6), taking any type of antibiotic during travel (OR 4.3, 95% CI 1.3-14.3) and travelling for any purpose other than business (OR 12.4, 95% CI 2.8-55.2). INTERPRETATION In this study, travel to India was associated with the highest risk of acquiring ESBL-producing E. coli relative to travel to other countries in South Asia. Nonbusiness travel, consuming foods with the local population and the use of antibiotics while travelling were associated with an increased risk of acquiring these antibiotic-resistant organisms while in India. Trial registration: ClinicalTrials.gov, no. NCT01296165.

OBJECTIVES To determine the proportion of true-positive blood culture results in children presenting to the ED with suspected appendicitis. To describe the current practice of obtaining blood cultures in children with suspected appendicitis. METHODS We performed a 2-year retrospective health record review of all children aged 2 through 17 years investigated for suspected appendicitis at a tertiary Pediatric Emergency Department. Subjects were identified by searching (a) institutional records for ICD-10-CA coding, (b) diagnostic imaging records of ultrasounds for appendicitis, and (c) surgical database records for nonincidental appendectomies. Abstracted demographic and clinical data were matched to regional laboratory services data to describe the performance and result of blood cultures. RESULTS Overall, 1315 children investigated for appendicitis were reviewed. Seven hundred fifty (57.0%) were girls, the average age was 11.7 years (SD, 4.0). Blood cultures were obtained in 288 (21.9%) of 1315 patients. Of the 11 (3.8%) cultures that were positive, only 1 (0.35%) was a true positive. Young age, high triage acuity, and presence of fever were associated with the acquisition of cultures (P < 0.001 for all). The proportion of children undergoing appendectomy and the negative appendectomy rate was similar between those with and without blood culture (P = 0.10 and P = 0.96, respectively). CONCLUSIONS True-positive blood cultures are very rare in children presenting to the ED with suspected appendicitis. Given the potential for false-positive cultures and the social/economic implications of initial testing/retesting of false positives, the use of routine blood cultures for children with suspected appendicitis is not supported.

IMPORTANCE: Detection of Clostridioides difficile has frequently been described in asymptomatic infants and children, but accurate estimates across the age spectrum are unavailable. OBJECTIVE: To assess the prevalence of C difficile detection among asymptomatic children across the age spectrum. DATA SOURCES: This systematic review and meta-analysis included a search of the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, CINAHL, Scopus, and Web of Science for articles published from January 1, 1990, to December 31, 2020. Search terms included Clostridium difficile, Peptoclostridium difficile, Clostridioides difficile, CDF OR CDI OR c diff OR c difficile, Clostridium infections OR cd positive diarrhea OR cd positive diarrhea OR Clostridium difficile OR Peptoclostridium difficile OR pseudomembranous colitis OR pseudomembranous enterocolitis, enterocolitis, and pseudomembranous. These were combined with the following terms: bacterial colonization and colonization OR colonized OR colonizing OR epidemiology OR prevalence OR seroprevalence. STUDY SELECTION: Studies were screened independently by 2 authors. Studies were included if they reported testing for C difficile among asymptomatic children (ie, children without diarrhea) younger than 18 years. DATA EXTRACTION AND SYNTHESIS: Data were extracted independently and in duplicate by 2 reviewers. Preferred Reporting Items for a Systematic Review and Meta-analysis (PRISMA) guidelines were used. Data were pooled using a random-effects model. MAIN OUTCOMES AND MEASURES: The primary outcome was prevalence of C difficile detection among asymptomatic children. Secondary outcomes included prevalence of toxigenic vs nontoxigenic strains of C difficile and prevalence of C difficile detection stratified by geographic region, income status, testing method, and year of testing. RESULTS: A total of 95 studies with 19 186 participants were included. Rates of detection of toxigenic or nontoxigenic C difficile were greatest among infants aged 6 to 12 months (41%; 95% CI, 32%-50%) and decreased to 12% (95% CI, 7%-18%) among children aged 5 to 18 years. The prevalence of toxigenic C difficile colonization was lower, peaking at 14% (95% CI, 8%-21%) among infants aged 6 to 12 months and decreasing to 6% (95% CI, 2%-11%) among children older than 5 years. Although prevalence differed by geographic region (ie, North and South America vs Europe: β, −0.151, P = .001; North and South America vs Western Pacific: β, 0.136, P = .007), there was no difference by testing method (ie, culture vs polymerase chain reaction: β, 0.069, P = .052; culture vs enzyme immunoassay: β, −0.178, P = .051), income class (low-middle income vs high income: β, −0.144, P = .23; upper-middle vs high income: β, −0.020, P = .64), or period (before 1990 vs 2010-2020: β, −0.125, P = .19; 1990-1999 vs 2010-2020: β, −0.037, P = .42; 2000-2009 vs 2010-2020: β, −0.006, P = .86). CONCLUSIONS AND RELEVANCE: In this systematic review and meta-analysis, C difficile colonization rates among children were greatest at 6 to 12 months of age and decreased thereafter. These estimates may provide context for interpreting C difficile test results among young children.

Background: Respiratory syncytial virus (RSV) infections are a common cause of morbidity and mortality in pediatric transplant recipients. From 2010 to 2013, the Canadian Paediatric Surveillance Program (CPSP) performed national active surveillance of RSV infections occurring in the 2 years following hematopoietic stem cell transplant (HSCT) or solid organ transplant (SOT). This study aimed to validate accuracy of reporting of inpatient cases of post-transplant RSV infections to the CPSP. Methods: Transplant recipients

Background Concern about adverse events following immunization is frequently cited by both those who receive or decline vaccines. Neurological adverse events are especially concerning. Objectives Our aim was to detect associations between seasonal influenza vaccination and the occurrence of severe anesthesia/paresthesia or severe headaches. Methods Data were analyzed from the Canadian National Vaccine Safety network. Events occuring on days 0–7 were self-reported and prevented daily activity, led to school or work absenteeism, or required medical attention. Controls were the previous year’s vaccinees; events in controls were collected prior to the start of the influenza vaccination program of each year (2012/13 through 2016/17). Multivariable logistic regression was used to determine the association between seasonal influenza vaccination and the occurrence of anesthesia/paresthesia or severe headaches. Results The total sample was 107,565 for investigating anesthesia/paresthesia and 97,420 for investigating severe headaches. Anesthesia/paresthesia was reported by 104/107,565 (0.10%) participants; 63/69,129 (0.09%) vaccinees and 41/38,436 (0.11%) controls (adjusted odds ratio (aOR) = 0.89; 95% CI = 0.60, 1.32). Severe headaches were reported by 1361/97,420 (1.40%) participants; 907/61,463 (1.48%) vaccinees and 454/35,957 (1.26%) controls (aOR = 1.21; 95% CI = 1.08, 1.36). No specific vaccine product was associated with severe headaches. Conclusions Our study found no association between severe anesthesia/paresthesia and seasonal influenza vaccination. While there was an association with severe headaches as an adverse event following influenza vaccination, the rates of these events are similar to rates reported from clinical trials and are not a cause for additional concern.

Background Pertussis immunization during pregnancy results in high pertussis antibody concentrations in young infants but may interfere with infant immune responses to post-natal immunization. Methods This phase IV, multi-country, open-label study assessed the immunogenicity and safety of infant primary vaccination with DTaP-HepB-IPV/Hib and 13-valent pneumococcal conjugate vaccine (PCV13). Enrolled infants (6–14 weeks old) were born to mothers who were randomized to receive reduced-antigen-content diphtheria-tetanus-three-component acellular pertussis vaccine (Tdap group) or placebo (control group) during pregnancy (270/7–366/7 weeks’ gestation) with crossover immunization postpartum. All infants received 2 or 3 DTaP-HepB-IPV/Hib and PCV13 doses according to national schedules. Immunogenicity was assessed in infants pre- and 1 month post-primary vaccination. The primary objective was to assess seroprotection/vaccine response rates for DTaP-HepB-IPV/Hib antigens 1 month post-primary vaccination. Results 601 infants (Tdap group: 296; control group: 305) were vaccinated. One month post-priming, seroprotection rates were 100% (diphtheria; tetanus), ≥98.5% (hepatitis B), ≥95.9% (polio) and ≥94.5% (Hib) in both groups. Vaccine response rates for pertussis antigens were significantly lower in infants whose mothers received pregnancy Tdap (37.5–77.1%) versus placebo (90.0–99.2%). Solicited and unsolicited adverse event rates were similar between groups. Serious adverse events occurred in 2.4% (Tdap group) and 5.6% (control group) of infants, none were vaccination-related. Conclusions Pertussis antibodies transferred during pregnancy may decrease the risk of pertussis infection in the first months of life but interfere with the infant’s ability to produce pertussis antibodies, the clinical significance of which remains unknown. Safety and reactogenicity results were consistent with previous experience. Clinical Trial Registration: ClinicalTrials.gov: NCT02422264.

Background: Pertussis immunization during pregnancy is recommended in many countries. Data from large randomized controlled trials are needed to assess the immunogenicity, reactogenicity and safety of this approach. Methods: This phase IV, observer-blind, randomized, placebo-controlled, multicenter trial assessed immunogenicity, transplacental transfer of maternal pertussis antibodies, reactogenicity and safety of a reduced-antigen-content diphtheria-tetanus-three-component acellular pertussis vaccine (Tdap) during pregnancy. Women received Tdap or placebo at 27–36 weeks’ gestation with crossover ≤ 72-hour-postpartum immunization. Immune responses were assessed before the pregnancy dose and 1 month after, and from the umbilical cord at delivery. Superiority (primary objective) was reached if the lower limits of the 95% confidence intervals (CIs) of the pertussis geometric mean concentration (GMC) ratios (Tdap/control) in cord blood were ≥ 1.5. Solicited and unsolicited adverse events (AEs) and pregnancy-/neonate-related AEs of interest were recorded. Results: 687 pregnant women were vaccinated (Tdap: N = 341 control: N = 346). Superiority of the pertussis immune response (maternally transferred pertussis antibodies in cord blood) was demonstrated by the GMC ratios (Tdap/control): 16.1 (95% CI: 13.5–19.2) for anti-filamentous hemagglutinin, 20.7 (15.9–26.9) for anti-pertactin and 8.5 (7.0–10.2) for anti-pertussis toxoid. Rates of pregnancy-/neonate-related AEs of interest, solicited general and unsolicited AEs were similar between groups. None of the serious AEs reported throughout the study were considered related to maternal Tdap vaccination. Conclusions: Tdap vaccination during pregnancy resulted in high levels of pertussis antibodies in cord blood, was well tolerated and had an acceptable safety profile. This supports the recommendation of Tdap vaccination during pregnancy to prevent early-infant pertussis disease. Clinical Trial Registration. ClinicalTrials.gov: NCT02377349., This work was supported by GlaxoSmithKline Biologicals S.A.

Little is known about the epidemiology and severity of gastroenteritis among children treated at home. We sought to compare illness severity and etiology between children brought for emergency department (ED) care to those managed at home (i.e., community). Prospective cohort study of children enrolled between December 2014 and December 2016 in two pediatric EDs in Alberta, Canada along with children treated at home after telephone triage (i.e., community). Primary outcomes were maximal frequency of vomiting and diarrhea in the 24-h pre-enrollment period; secondary outcomes included etiologic pathogens, dehydration severity, future healthcare visits, and treatments provided. A total of 1613 patients (1317 ED, 296 community) were enrolled. Median maximal frequency of vomiting was higher in the ED cohort (5 (3, 10) vs. 5 (2, 8); P < 0.001). Proportion of children with diarrhea and its 24-h median frequency were lower in the ED cohort (61.3 vs. 82.8% and 2 (0, 6) vs. 4 (1, 7); P < 0.001, respectively). In regression analysis, the ED cohort had a higher maximum number of vomiting episodes pre-enrollment (incident rate ratio (IRR) 1.25; 95% CI 1.12, 1.40) while the community cohort had higher maximal 24-h period diarrheal episodes (IRR 1.20; 95% CI 1.01, 1.43). Norovirus was identified more frequently in the community cohort (36.8% vs. 23.6%; P < 0.001). Children treated in the ED have a greater number of vomiting episodes; those treated at home have more diarrheal episodes. Norovirus is more common among children treated symptomatically at home and thus may represent a greater burden of disease than previously thought.

Data are lacking regarding the impact of visible pigment on rectal swab diagnostic accuracy. We describe the test characteristics of rectal swabs with and without pigment in children with gastroenteritis. Between December 2014 and September 2017, children (age

Although enteric multianalyte syndromic panels are increasingly employed, direct comparisons with traditional methods and the inclusion of host phenotype correlations are limited. Luminex xTAG gastrointestinal pathogen panel (GPP) and culture results are highly concordant. However, phenotypic and microbiological confirmatory testing raises concerns regarding the accuracy of the GPP, especially for Salmonella spp. A total of 3,089 children with gastroenteritis submitted stool specimens, rectal swab specimens, and clinical data. The primary outcome was bacterial pathogen detection agreement for shared targets between culture and the Luminex xTAG GPP. Secondary analyses included phenotype assessment, additional testing of GPP-negative/culture-positive isolate suspensions with the GPP, and in-house and commercial confirmatory nucleic acid testing of GPP-positive/culture-negative extracts. The overall percent agreement between technologies was >99% for each pathogen. Salmonella spp. were detected in specimens from 64 participants: 12 (19%) by culture only, 9 (14%) by GPP only, and 43 (67%) by both techniques. Positive percent agreement for Salmonella spp. was 78.2% (95% confidence interval [CI], 64.6%, 87.8%). Isolate suspensions from the 12 participants with specimens GPP negative/culture positive for Salmonella tested positive by GPP. Specimens GPP positive/culture negative for Salmonella originated in younger children with less diarrhea and more vomiting. GPP-positive/culture-negative specimen extracts tested positive using additional assays for 0/2 Campylobacter-positive specimens, 0/4 Escherichia coli O157-positive specimens, 0/9 Salmonella-positive specimens, and 2/3 Shigella-positive specimens. For both rectal swab and stool samples, the median cycle threshold (CT) values, determined using quantitative PCR, were higher for GPP-negative/culture-positive samples than for GPP-positive/culture-positive samples (for rectal swabs, 36.9 [interquartile range {IQR}, 33.7, 37.1] versus 30.0 [IQR, 26.2, 33.2], respectively [P = 0.002]; for stool samples, 36.9 [IQR, 33.7, 37.1] versus 29.0 [IQR, 24.8, 30.8], respectively [P = 0.001]). GPP and culture have excellent overall agreement; however, for specific pathogens, GPP is less sensitive than culture and, notably, identifies samples false positive for Salmonella spp.

Background The ability to identify bacterial pathogens that necessitate specific clinical management or public health action in children with acute gastroenteritis is crucial to patient care and public health. However, existing stool-testing guidelines offer inconsistent recommendations, and their performance characteristics are unknown. We evaluated 6 leading gastroenteritis guidelines (eg, those of the Centers for Disease Control and Prevention and Infectious Disease Society of America) that recommend when to test children’s stool for bacterial enteropathogens. Methods Via 2 emergency departments in Alberta, Canada, we enrolled 2447 children Results Outcome data were available for 2391 (97.7%) participants, and 6% (144/2391) of participants tested positive for a bacterial enteropathogen. Guideline sensitivity ranged from 25.8% (95% confidence interval [CI] 18.7–33.0%) to 66.9% (95% CI 59.3–74.6%), and varied for individual pathogens. Guideline specificity for all bacterial enteropathogens ranged from 63.6% (95% CI 61.6–65.6%) to 96.5% (95% CI 95.7–97.2%). Conclusions No guideline provided optimally balanced performance. The most sensitive guidelines missed one-third of cases and would drastically increase testing volumes. The most specific guidelines missed almost 75% of cases.

To characterize the pain experienced by children with acute gastroenteritis (AGE) in the 24 hours before emergency department (ED) presentation. Secondary objectives included characterizing ED pain, discharge recommendations, overall analgesic use, and factors that influenced analgesic use and pain severity.A prospective cohort was recruited from 2 pediatric EDs (December 2014 to September 2017). Eligibility criteria included18 years of age, AGE (≥3 episodes of diarrhea or vomiting in the previous 24 hours), and symptom duration7 days at presentation.We recruited 2136 patients, median age 20.8 months (IQR 10.4, 47.4) and 45.8% (979/2136) female. In the 24 hours before enrollment, most caregivers reported moderate (28.6% [610/2136, 95% CI 26.7-30.5]) or severe (46.2% [986/2136, CI 44.0-48.3]) pain for their child. In the ED, they reported moderate (31.1% [664/2136, 95% CI 29.1-33.1]) or severe ([26.7% [571/2136, 95% CI 24.9-28.7]) pain; analgesia was provided to 21.2% (452/2131). The most common analgesics used in the ED were acetaminophen and ibuprofen. At discharge, these were also most commonly recommended. Factors associated with greater analgesia use in the ED were high pain scores during the index visit, having a primary care physician, earlier presentation to emergency care, fewer diarrheal episodes, presence of fever, and hospitalization at index visit.Most caregivers of children presenting to the ED with AGE reported moderate or severe pain, both before and during their visit. Future research should focus on the development of effective, safe, and timely pain management plans.

Background The diversity of Canadian infant meningococcal C conjugate (MenC) vaccine programs is unique among countries providing MenC vaccines and offers a valuable opportunity to determine the optimal vaccine program. This longitudinal study assessed differences in seroprotection by 3 different vaccine schedules in children two years after receiving either 1 toddler MenC vaccine dose (1 dose), 1 infant and 1 toddler dose (2 doses), or 2 infant and 1 toddler MenC vaccine dose (3 doses). Methods Three similar cohorts of healthy infants from 1, 2 and 3 dose program areas were enrolled before to their 12 month toddler dose and vaccinated with MenC-tetanus toxoid (MenC-TT) conjugate vaccine. Sera obtained 2 years later were assayed for serogroup C bactericidal activity using standardized procedures with rabbit as the exogenous complement source. Serum bactericidal activity titers ≥1:8 were considered protective. Results Results were available for 384 children. Rates of seroprotection at 36 months of age were significantly different between the 1 and 3 dose programs, but confidence intervals overlapped between the 1 and 2 dose programs and between the 2 and 3 dose programs: 1 dose 92% (95% confidence interval: 86%-96%) versus 99% (95%-100%) with 2 doses and 100% (97%-100%) with 3 doses. Geometric mean titers were significantly different at 12.1 (10.8-13.5), 32.4 (28.9-36.2) and 50.6 (45.7-55.9) in the 1, 2 and 3 dose programs, respectively. Conclusions At 36 months of age, evidence of seroprotection remained for greater than 90% of participants. Our results indicate that 1 toddler dose or 1 infant plus 1 toddler dose with MenC-TT vaccine provides seroprotection against MenC disease in early childhood.

BACKGROUND Pneumococcal conjugate vaccine (PCV) was introduced into Alberta, Canada's routine childhood immunization programs in 2002 (7-valent [PCV7]) and 2010 (13-valent [PCV13]). We assessed the effect of these programs on the epidemiology of invasive pneumococcal disease (IPD) to determine if PCV-associated indirect protection was relatively reduced in adults with underlying comorbidities. METHODS Demographic and clinical data were collected by a prospective, population-based surveillance system in Calgary, Alberta, Canada, from January 2000 to December 2013. An indirect cohort study design was used to assess for changes in the proportion of IPD cases with underlying comorbidities. RESULTS There were 1598 overall and 1346 adult IPD cases from 1 January 2000 to 31 December 2013. Overall IPD incidence decreased 33% (age 0-5 months), 86% (6-23 months), 67% (2-4 years), 26% (5-17 years), 22% (18-64 years), 36% (65-84 years), and 42% (≥85 years) from the prevaccine (January 2000-July 2002) to the post-PCV13 (July 2010-December 2013) period. Over the same timeframe, PCV7 serotype disease incidence declined to ≤1 case per 100 000 persons in all age groups. Neither the proportion of adult cases with immunocompetent comorbidities (relative risk ratio [RRR], 0.93; 95% confidence interval [CI], .62-1.40) nor immunocompromising comorbidities (RRR, 0.99; 95% CI, .61-1.61) differed between the pre-PCV period and post-PCV era. CONCLUSIONS Childhood PCV programs have provided considerable benefit, with substantial declines in overall and vaccine-serotype IPD in vaccinated children and in unvaccinated persons. Conjugate vaccine-associated indirect protection for adults with comorbidities was similar to that for healthy adults.

Background Antibiotic administration to individuals with Shiga toxin-producing Escherichia coli (STEC) infection remains controversial. We assessed if antibiotic administration to individuals with STEC infection is associated with development of hemolytic uremic syndrome (HUS). Methods The analysis included studies published up to 29 April 2015, that provided data from patients (1) with STEC infection, (2) who received antibiotics, (3) who developed HUS, and (4) for whom data reported timing of antibiotic administration in relation to HUS. Risk of bias was assessed; strength of evidence was adjudicated. HUS was the primary outcome. Secondary outcomes restricted the analysis to low-risk-of-bias studies employing commonly used HUS criteria. Pooled estimates of the odds ratio (OR) were obtained using random-effects models. Results Seventeen reports and 1896 patients met eligibility; 8 (47%) studies were retrospective, 5 (29%) were prospective cohort, 3 (18%) were case-control, and 1 was a trial. The pooled OR, including all studies, associating antibiotic administration and development of HUS was 1.33 (95% confidence interval [CI], .89-1.99; I(2) = 42%). The repeat analysis including only studies with a low risk of bias and those employing an appropriate definition of HUS yielded an OR of 2.24 (95% CI, 1.45-3.46; I(2) = 0%). Conclusions Overall, use of antibiotics was not associated with an increased risk of developing HUS; however, after excluding studies at high risk of bias and those that did not employ an acceptable definition of HUS, there was a significant association. Consequently, the use of antibiotics in individuals with STEC infections is not recommended.

Serious infections in infants require urgent treatment. Microbiology of bacterial isolates obtained from children younger than 90 days of was reviewed. Nine-hundred thirty-two infants were identified (mean age of 39 days). Seventy-four percent of organisms obtained were relevent. Common pathogens identified were Escherichia coli, Streptococcus agalactiae and Staphylococcus aureus. Emergence of S. aureus (18% methicillin resistant S. aureus (MRSA)) and ampC producing enterobacteriaceae requires prompt attention.

Background. We sought to develop diagnostic test guidance definitions for pediatric enteric infections to facilitate the interpretation of positive test results in the era of multianalyte molecular diagnostic test platforms.Methods. We employed a systematic, two-phase, modified Delphi consensus process consisting of three web-based surveys and an expert panel face-to-face meeting. In phase 1, we surveyed an advisory panel of North American experts to select pathogens requiring diagnostic test guidance definition development. In phase 2, we convened a 14-member expert panel to develop, refine, and select the final definitions through two web-based questionnaires interspersed with a face-to-face meeting. Both questionnaires asked panelists to rate the degree to which they agreed that if the definition is met the pathogen is likely to be causative of clinical illness.Results. The advisory panel survey identified 19 pathogens requiring definitions. In the expert panel premeeting survey, 13 of the 19 definitions evaluated were rated as being highly likely (“agree” or “strongly agree”) to be responsible for acute gastroenteritis symptoms by ≥67% of respondent panel members. The definitions for the remaining six pathogens (Aeromonas, Clostridium difficile, Edwardsiella,nonenteric adenovirus, astrovirus, andEntamoeba histolytica) were indeterminate. After the expert panel meeting, only two of the modified definitions,C. difficileandE. histolytica/dispar, failed to achieve thea priorispecified threshold of ≥67% agreement.Conclusions.We developed diagnostic test guidance definitions to assist healthcare providers for 17 enteric pathogens. We identified two pathogens that require further research and definition development.

To evaluate the relationship between individual bacterial and viral pathogens and disease severity.Children18 years with three or more episodes of vomiting and/or diarrhoea were enrolled in two Canadian paediatric emergency departments between December 2014 and August 2016. Specimens were analysed employing molecular panels, and outcome data were collected 14 days after enrolment. The primary outcome was severe disease over the entire illness (symptom onset until 14-day follow-up), quantified employing the Modified Vesikari Scale (MVS) score. The score was additionally analysed in two other time periods: index (symptom onset until enrolment) and follow-up (enrolment until 14-day follow-up).Median participant age was 20.7 (IQR: 11.3, 44.2) months; 47.4% (518/1093) and 73.4% (802/1093) of participants had index and total MVS scores ≥11, respectively. The most commonly identified pathogens were rotavirus (289/1093; 26.4%) and norovirus (258/1093; 23.6%). In multivariable analysis, severe disease over the entire illness was associated with rotavirus (OR = 9.60; 95%CI: 5.69, 16.19), Salmonella (OR = 6.61; 95%CI: 1.50, 29.17), adenovirus (OR = 2.53; 95%CI: 1.62, 3.97), and norovirus (OR = 1.43; 95%CI: 1.01, 2.01). Pathogens associated with severe disease at the index visit were: rotavirus only (OR = 6.13; 95%CI: 4.29, 8.75), Salmonella (OR = 4.59; 95%CI: 1.71, 12.29), adenovirus only (OR = 2.06; 95%CI: 1.41, 3.00), rotavirus plus adenovirus (OR = 3.15; 95%CI: 1.35, 7.37), and norovirus (OR = 0.68; 95%CI: 0.49, 0.94). During the follow-up period, rotavirus (OR = 2.21; 95%CI: 1.50, 3.25) and adenovirus (OR = 2.10; 95%CI: 1.39, 3.18) were associated with severe disease.In children presenting for emergency department care with acute gastroenteritis, pathogens identified were predominantly viruses, and several of which were associated with severe disease. Salmonella was the sole bacterium independently associated with severe disease.

Introduction: Bacterial meningitis is a severe intracranial infection with a high complication rate. Neurological morbidity relates to parenchymal involvement where vascular mechanisms and stroke may predominate. Here, we systematically identified all neonates and children with bacterial meningitis and compared those with and without MRI-confirmed stroke. We hypothesized that patterns of stroke would correlate with causative organism and neurological outcome. Methods: Population-based (2.2 million), ten-year retrospective (2002-2012) cross-sectional study in Southern Alberta, Canada. Inclusion criteria were: (1) age from newborn (including prematurity) to 18 years, (2) brain MRI including DWI during admission, and (3) laboratory confirmed acute bacterial meningitis. Demographics, clinical presentations, risk factors, and laboratory findings were extracted. Original imaging was blindly reviewed and classified for stroke and injury pattern. Outcomes were extrapolated to the Pediatric Stroke Outcome Measure (PSOM). Results: Twenty-four patients had confirmed bacterial meningitis and acute MRI (6 neonates, 83% male, and 18 children, mean age 3.14+/-3.9 years, 67% male). Arterial ischemic stroke was confirmed in 9/24 (38%). Strokes were often multifocal (89%), particularly in neonates (100%). Subjects with stroke were more likely to have longer duration of illness prior to presentation, meningismus, prolonged fever, seizures, and new focal neurological signs. The most common organisms were S. pneumonia in older children (44%) and group B streptococcus in neonates (33%). Three patients received steroids, 3 ASA and 1 heparin and ASA. Mortality was 22% in children with stroke and zero in those without (p=0.16). Survivors with stroke were more likely to have motor deficit (71% vs. 25%, p = 0.07), cognitive deficit (75% vs. 38%, p = 0.5), and speech deficit (60% vs. 10%, p = 0.08). Conclusions: More than a third of children with bacterial meningitis warranting MRI have stroke. Associations include longer duration of illness, meningismus, focal neurological signs and common causative organisms. Stroke was associated with higher mortality and morbidity, warranting consideration of increased MRI screening and new approaches to treatment.

Introduction: Although acute gastroenteritis is an extremely common childhood illness, there is a paucity of literature characterizing the associated pain and its management. Our primary objective was to quantify the pain experienced by children with acute gastroenteritis in the 24-hours prior to emergency department (ED) presentation. Secondary objectives included describing maximum pain, analgesic use, discharge recommendations, and factors that influenced analgesic use in the ED. Methods: Study participants were recruited into this prospective cohort study by the Alberta Provincial Pediatric EnTeric Infection TEam between January 2014 and September 2017. This study was conducted at two Canadian pediatric EDs; the Alberta Children's Hospital (Calgary) and the Stollery Children's Hospital (Edmonton). Eligibility criteria included < 18 years of age, acute gastroenteritis (□ 3 episodes of diarrhea or vomiting in the previous 24 hours), and symptom duration □ 7 days. The primary study outcome, caregiver-reported maximum pain in the 24-hours prior to presentation, was assessed using the 11-point Verbal Numerical Rating Scale. Results: We recruited 2136 patients, median age 20.8 months (IQR 10.4, 47.4); 45.8% (979/2136) female. In the 24-hours prior to enrolment, 28.6% (610/2136) of caregivers reported that their child experienced moderate (4-6) and 46.2% (986/2136) severe (7-10) pain in the preceding 24-hours. During the emergency visit, 31.1% (664/2136) described pain as moderate and 26.7% (571/2136) as severe. In the ED, analgesia was provided to 21.2% (452/2131) of children. The most commonly administered analgesics in the ED were ibuprofen (68.1%, 308/452) and acetaminophen (43.4%, 196/452); at home, acetaminophen was most commonly administered (77.7%, 700/901), followed by ibuprofen (37.5%, 338/901). Factors associated with analgesia use in the ED were greater pain scores during the visit, having a primary-care physician, shorter illness duration, fewer diarrheal episodes, presence of fever and hospitalization. Conclusion: Although children presenting to the ED with acute gastroenteritis experience moderate to severe pain, both prior to and during their emergency visit, analgesic use is limited. Future research should focus on appropriate pain management through the development of effective and safe pain treatment plans.

There is mounting evidence that the recent resurgence of pertussis in many countries is in part related to the acellular vaccine, which has been administered in Canada since 1997. This vaccine elicits a different cell-mediated immune response than the previously used whole-cell vaccine, and its effectiveness wanes over time. The aim of this study is to understand the immunological, demographic and clinical factors that mediate protection from pertussis on exposure.This is a household case-control study protocol. Following notification of an index case in a household, a study team will conduct a home visit to collect data and biological specimens. The study team will return to the household 8 weeks from the onset of illness in the index case. The Th1, Th2 and Th17 responses, cytokine expression, IgG subclass, blood cell counts and presence ofThe results of this study will be essential for understanding the immune response required for protection from infection with

A previous study in Calgary showed that travel to India was associated with high risk of community-onset infections with extended-spectrum β-lactamase (ESBL)-producingA total of 149 travellers participated between January 2012 and July 2014; of these, 116 (78%) provided rectal swabs upon return to Calgary and completed both pre- and post-travel questionaires. Of the 109 travellers without colonization with ESBL-producingIn this study, travel to India was associated with the highest risk of acquiring ESBL-producing