Immunization Monitoring Program Research Articles

42 Clinical features and severity of COVID-19 with respiratory virus coinfections versus SARS-CoV-2 monoinfection in hospitalized children: A Canadian national surveillance study

Abstract Background The co-circulation of SARS-CoV-2 alongside other respiratory viruses has led to the risk of coinfections, potentially intensifying the severity of cases, especially in children. Objectives This study examined the epidemiology, clinical characteristics, and outcomes of SARS-CoV-2 respiratory virus coinfections in comparison to SARS-CoV-2 monoinfections in hospitalized children. Design/Methods A nationwide surveillance study was conducted to assess paediatric COVID-19-related hospitalizations across Canada from April 2020 to May 2022. Data were captured through two datasets covering ~90% of all Canadian tertiary-care paediatric beds: The Canadian Paediatric Surveillance Program and the Canadian Immunization Monitoring Program, ACTive. Coinfections were defined as the simultaneous detection of SARS-CoV-2 and ≥1 other respiratory virus. Severe infection was defined as intensive care, ventilatory, or hemodynamic support needs, organ systems complications, or death. Variables and outcomes were summarized and compared, and risk ratios were computed using Poisson regression, adjusting for age, gender, comorbid conditions, SARS-CoV-2 lineage, and vaccination status. Results Out of 1501 COVID-19-related hospitalizations, 163 (10.9%) had documented coinfections with 44/163 [27%] involving SARS-COV-2 plus ≥2 other respiratory viruses. The majority of SARS-CoV-2 monoinfections (1176/1501, 87.9%) and coinfections (139/163, 85.3%) belonged to the Omicron era (Figure A). RSV (66/163, 40.5%) and Enterovirus/rhinovirus (61/163, 37.4%) coinfections were the most common. Coinfection cases were significantly younger than monoinfection cases (median age 1.2 [IQR:0.3-3.3] vs 1.6 [IQR:0.3-7.0] years, p=0.04). Overall, severe disease was more common among cases with any coinfection (38.0%) than SARS-CoV-2 monoinfection (25.7%; adjusted risk ratio 1.45, 95% confidence interval 1.17-1.80) (Figure B). In particular, we observed that severe outcomes were significantly higher in SARS-CoV-2 coinfections compared to monoinfections during the Omicron era (Figure C-D). Overall, 26/61 (42.6%) Enterovirus/Rhinovirus and 20/66 (30.3%) RSV coinfections were associated with severe outcomes. Conclusion Children with documented coinfections had more severe respiratory disease compared to SARS-COV-2 monoinfections. However, children with severe COVID-19 may have been more likely tested for multiple viruses, leading to a risk of underestimation of coinfections among children with milder disease. Further work is needed to assess how different virus coinfections may affect children and which, if any, may be a predominant driver of disease severity. 1Severe disease was defined as intensive care, ventilatory, or hemodynamic support requirements, organ system complications, or death. 2Lineage was first assigned based on available genetic sequencing data. If missing, lineage was imputed based on the dominant circulating lineage at the provincial level according to the GISAID database.

Streptococcus pneumoniae-associated hemolytic uremic syndrome Canadian Immunization Monitoring Program ACTive National Pediatric Surveillance (1991 to 2019)

Streptococcus pneumoniae-associated hemolytic uremic syndrome Canadian Immunization Monitoring Program ACTive National Pediatric Surveillance (1991 to 2019)

Bloodstream Infections in Children Hospitalized for Influenza, the Canadian Immunization Monitoring Program Active.

We aimed to estimate the proportion of children hospitalized for influenza whose illness was complicated by bloodstream infection, describe their clinical course, and identify the factors associated with bloodstream infection. We performed active surveillance for laboratory-confirmed influenza hospitalizations among children ≤16 years old at the 12 Canadian Immunization Monitoring Program Active hospitals, from the 2010-2011 to 2020-2021 influenza seasons. Factors associated with bloodstream infection were identified using multivariable logistic regression analyses. Among 9179 laboratory-confirmed influenza hospital admissions, bloodstream infection occurred in 87 children (0.9%). Streptococcus pyogenes (22%), Staphylococcus aureus (18%) and Streptococcus pneumoniae (17%) were the most common bloodstream infection pathogens identified. Children with cancer [adjusted odds ratio (aOR): 2.78; 95% confidence interval (CI): 1.23-5.63], a laboratory-confirmed nonbloodstream bacterial infection (aOR: 14.1; 95% CI: 8.04-24.3) or radiographically-confirmed pneumonia (aOR: 1.87; 95% CI: 1.17-2.97) were more likely to experience a bloodstream infection, whereas children with chronic lung disorders were less likely (aOR: 0.41; 95% CI: 0.19-0.80). Disease severity markers such as intensive care unit admission (aOR: 2.11; 95% CI: 1.27-3.46), mechanical ventilation (aOR: 2.84; 95% CI: 1.63-4.80) and longer hospital length of stay (aOR: 1.02; 95% CI: 1.01-1.03) were associated with bloodstream infection. Bloodstream infection also increased the odds of death (aOR: 13.0; 95% CI: 4.84-29.1) after adjustment for age, influenza virus type and the presence of any at-risk chronic condition. Bloodstream infections, although infrequent, are associated with intensive care unit admission, mechanical ventilation, increased hospital length of stay and in-hospital mortality, thus requiring increased levels of care among pediatric influenza hospitalizations.

2613. Pediatric respiratory syncytial virus hospitalizations, 2017 to 2022, the Canadian Immunization Monitoring Program Active (IMPACT)

Abstract Background Respiratory syncytial virus (RSV) is a leading cause of pediatric hospitalizations. We aimed to describe the epidemiology and burden of RSV-associated hospitalizations among children in Canadian pediatric centers from 2017 to 2022, including changes during the COVID-19 pandemic. Methods We performed active surveillance for hospitalized children 0 to 16 years of age with laboratory confirmed RSV at 13 Canadian Immunization Monitoring Program Active (IMPACT) pediatric hospitals during 5 seasons (2017-18 to 2021-22). Proportions of RSV hospitalizations over all-cause hospitalizations over time, and intensive care unit (ICU) admissions, prolonged admissions (≥ 7-days) and mortality proportions were calculated, overall and by age groups and regions. RSV hospitalization-associated burden was compared for 2021-22 to the pre-pandemic period of 2017-18 to 2019-20. Seasonality was described using epidemic curves. Results Among 11,014 RSV-associated hospitalizations 6,035 (54.8%) were male and 5,488 (50%) were aged < 6 months. Overall, 2,594 (23.6%) were admitted to ICU, of which 60.8% were aged < 6 months old. The median hospital stay was 4 days (interquartile range: 2-6). The mean number of hospitalizations during the pre-pandemic seasons was 2,522. Only 58 cases were reported in 2020-21, followed by 3,170 in 2021-22. The proportion of RSV hospitalizations over all-cause hospitalizations rose from 3.2% pre-pandemic to 4.5% in 2021-22 (difference 1.3% [95%CI 0.8-1.8]; p=0.07 after multiplicity adjustment). One province, Quebec, had a significant increase in RSV-hospitalization proportion in 2021-22 (2.5 percentage points, 95%CI 1.7-3.2, adjusted p-value 0.045). Age, sex, ICU admission, prolonged length of stay(≥7-days) and mortality proportions did not change in 2021-22 compared to the pre-pandemic period. Interregional differences in RSV seasonality were accentuated in 2021-22. Weekly RSV-associated hospital admissions in children aged 0 to 16 years at IMPACT centers, 2017-2022, by season Monthly RSV-associated hospital admissions in children aged 0 to 16 years at IMPACT centers, 2017-2022, by province Conclusion RSV hospitalization burden in Canadian pediatric hospitals is substantial, especially in infants aged < 6 months. Following a near absence in 2020-21, RSV hospitalizations increased in the 2021-22 season, but severity of illness remained similar to the pre-pandemic period. These data will aid planning of RSV prevention strategies. Disclosures Nirma K. Vadlamudi, MPH, PhD, Broadstreet HEOR: Personal fees outside of the submitted work Scott Halperin, MD, CanSino: Grant/Research Support|CanSino: served on ad hoc advisory board|GlaxoSmithKline: Grant/Research Support|GlaxoSmithKline: served on ad hoc advisory board|Merck: Grant/Research Support|Merck: served on ad hoc advisory board|Moderna: Grant/Research Support|Moderna: served on ad hoc advisory board|Pfizer,: Grant/Research Support|Pfizer,: served on ad hoc advisory board|Sanofi-Pasteur: Grant/Research Support|Sanofi-Pasteur: served on ad hoc advisory board|Seqirus: Grant/Research Support|Seqirus: served on ad hoc advisory board|VBI Vaccines: Grant/Research Support|VBI Vaccines: served on ad hoc advisory board Joanne M. Langley, MD, CanSino: Grant/Research Support|Entos: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Merck: Grant/Research Support|Moderna: Grant/Research Support|Pfizer: Grant/Research Support|Sanofi-Pasteur: Grant/Research Support|Seqirus: Grant/Research Support|Symvivo: Grant/Research Support|VBI Vaccines: Grant/Research Support Shaun Morris, MD, MPH, DTM&H, FRCPC, FAAP, GlaxoSmithKline: Honoraria|JNJ China: Honoraria|Merck: served on ad hoc advisory board|Pfizer: Grant/Research Support|Pfizer: served on ad-hoc advisory board|Sanofi-Pasteur: served on ad-hoc advisory board Jeffrey Pernica, MD, MSc, FRCPC, DTMH, MedImmune: Grant/Research Support|Merck: Grant/Research Support Manish Sadarangani, BM BCh, FRCPC, DPhil, GlaxoSmithKline: Grant/Research Support|Merck: Grant/Research Support|Moderna: Grant/Research Support|Pfizer: Grant/Research Support|Sanofi Pasteur: Grant/Research Support|Seqirus: Grant/Research Support|Symvivo: Grant/Research Support|VBI Vaccines: Grant/Research Support Jesse Papenburg, MD, AstraZeneca: Personal fees outside of the submitted work|MedImmune: Grant/Research Support|Merck: Grant/Research Support|Merck: Personal fees outside of the submitted work

Antibiotic use in children hospitalised for influenza, 2010-2021: the Canadian Immunization Monitoring Program Active (IMPACT).

To determine characteristics associated with inappropriate antibiotic use amongst children hospitalised for influenza. We performed active surveillance for laboratory-confirmed influenza hospitalizations amongst children ≤ 16years old at the 12 Canadian Immunization Monitoring Program Active hospitals, from September 2010 to August 2021. Antibiotic use was presumed appropriate if any of the following indications were met: age < 1month, immunocompromised, hemoglobinopathy, laboratory-confirmed bacterial infection, radiographically confirmed pneumonia, admission to an intensive care unit and mechanical ventilation. Regression analyses were used to identify baseline and clinical characteristics associated with antibiotic use amongst patients without an appropriate indication. Amongst 8971 children, 6424 (71.6%) received any antibiotics during their hospitalisation. Amongst the 4429 children without an appropriate indication, 2366 (53.2%) received antibiotics. Antibiotic use amongst children without appropriate indication differed between study centres, ranging from 33.2% to 66.1% (interquartile range [IQR] 50.6-56.3%); it did not change significantly over time (p-value for trend = 0.28). In multivariable analyses, older age (adjusted odds ratio [aOR] 0.97, 95% confidence interval [CI] 0.96-0.99), presence of any high-risk condition (aOR 0.80, 95% CI 0.70-0.92), influenza virus type B (aOR 0.8, 95% CI 0.70-0.91) and croup (aOR 0.64, 95% CI 0.49-0.83) were associated with less, whilst fever ≥ 38.5°C (aOR 1.82, 95% CI 1.42-2.35) and hospitalisation duration (aOR 1.12, 95% CI 1.09-1.15) were associated with more inappropriate antibiotic use. Over two-third of children hospitalised for influenza received antibiotics, including over half of those without an appropriate indication for antibiotic treatment. Differences amongst study centres suggest the importance of contextual determinants of antibiotic use.

The success of publicly funded rotavirus vaccine programs for preventing community- and hospital-acquired rotavirus infections in Canadian pediatric hospitals: an observational study.

Canadian immunization programs for rotavirus started in 2011. We sought to determine their effect on the burden of community-acquired admissions and hospital-acquired rotavirus at pediatric hospitals. The Canadian Immunization Monitoring Program Active (IMPACT) network conducted active surveillance for rotavirus-positive hospital admissions between 2005 and 2020 at 12 pediatric hospitals. We used yearly rates of community-acquired rotavirus per 10 000 admissions and hospital-acquired rotavirus infections per 1000 patient-days to determine changes in the pre- and post-vaccine program periods. During the 15-year study period, 5691 rotavirus hospital admissions and hospital-acquired infections were detected, including 4323 (76%) community-acquired infections and 1368 (24%) hospital-acquired infections. The average community-acquired rate in the pre-vaccine period was 60.3 (95% confidence interval [CI] 53.7-68.3) per 10 000 admissions, with a decline to 11.0 (95% CI 7.5-15.1) per 10 000 admissions in the post-vaccine period, resulting in an average reduction of 81.7% (95% CI 74.4%-87.8%). The rate of hospital-acquired rotavirus declined from 0.35 (95% CI 0.29-0.41) per 1000 patient-days in the pre-vaccine period to 0.05 (95% CI 0.03-0.07) per 1000 patient-days in the post-vaccine period, resulting in an 85.3% (95% CI 77.7%-91.9%) average decline. Herd protection was present among children aged 2-16 years. Although start dates of rotavirus vaccine programs across provinces varied, there was around an 80% average decrease in both community-acquired and hospital-acquired rotavirus infections at pediatric hospitals in Canada in the 1- to 9-year interval after implementation of rotavirus vaccine programs. Herd protection is an important aspect of rotavirus vaccines for other children who are not vaccine eligible, and rotavirus vaccines continue to provide important benefits both for children and health care systems.

Pediatric RSV-Associated Hospitalizations Before and During the COVID-19 Pandemic.

Respiratory syncytial virus (RSV) is a leading cause of pediatric hospitalizations. To describe the epidemiology and burden of RSV-associated hospitalizations among children and adolescents in Canadian tertiary pediatric hospitals from 2017 to 2022, including changes during the COVID-19 pandemic. This cross-sectional study was conducted during 5 RSV seasons (2017-2018 to 2021-2022) at 13 pediatric tertiary care centers from the Canadian Immunization Monitoring Program Active (IMPACT) program. Hospitalized children and adolescents aged 0 to 16 years with laboratory-confirmed RSV infection were included. The proportion of all-cause admissions associated with RSV and counts and proportions of RSV hospitalizations with intensive care unit (ICU) admission, prolonged stay (≥7 days), and in-hospital mortality were calculated overall and by season, age group, and region. Seasonality was described using epidemic curves. RSV hospitalizations for 2021-2022 were compared with those in the prepandemic period of 2017-2018 through 2019-2020. Bonferroni corrections were applied to P values to adjust for multiple statistical comparisons. Among 11 014 RSV-associated hospitalizations in children and adolescents (6035 hospitalizations among male patients [54.8%]; 5488 hospitalizations among patients aged <6 months [49.8%]), 2594 hospitalizations (23.6%) had admission to the ICU, of which 1576 hospitalizations (60.8%) were among children aged less than 6 months. The median (IQR) hospital stay was 4 (2-6) days. The mean (SD) number of RSV-associated hospitalizations during prepandemic seasons was 2522 (88.8) hospitalizations. There were 58 hospitalizations reported in 2020-2021, followed by 3170 hospitalizations in 2021-2022. The proportion of all-cause hospitalizations associated with RSV increased from a mean of 3.2% (95% CI, 3.1%-3.3%) before the pandemic to 4.5% (95% CI, 4.3%-4.6%) in 2021-2022 (difference, 1.3 percentage points; 95% CI, 1.1-1.5 percentage points; corrected P < .001). A significant increase in RSV-associated hospitalizations was found in 2021-2022 for 3 provinces (difference range, 2.5 percentage points; 95% CI, 1.4-3.6 percentage points for Quebec to 2.9 percentage points; 95% CI, 1.4-3.5 percentage points for Alberta; all corrected P < .001). Age, sex, ICU admission, prolonged length of stay, and case fatality rate did not change in 2021-2022 compared with the prepandemic period. Interregional differences in RSV seasonality were accentuated in 2021-2022, with peaks for 1 province in October, 4 provinces in December, and 3 provinces in April, or May. This study found that the burden of RSV-associated hospitalizations in Canadian pediatric hospitals was substantial, particularly among infants aged less than 6 months, and RSV hospitalizations increased in 2021-2022 compared with the prepandemic period, while severity of illness remained similar. These findings suggest that RSV preventive strategies for infants aged less than 6 months would be associated with decreased RSV disease burden in children.

24 Characteristics and Outcomes of Hospitalized Children by SARS-Cov-2 Lineage: An IMPACT Surveillance Network Analysis

Abstract Introduction/Background Changes in relative virulence of SARS-CoV-2 lineages among children remain poorly understood, yet are important considerations for vaccination and health resource management. Further evidence is needed to assess the burden of severe paediatric COVID-19 due to the Omicron variant. Objectives In this study, we aimed to compare presenting features and disease severity among hospitalized children with COVID-19 in Canada by SARS-CoV-2 lineage. Design/Methods Data were collected during two national surveillance studies: the Canadian Paediatric Surveillance Program (April 2020–May 2021) and the Canadian Immunization Monitoring Program, ACTive (June 2021–May 2022). Cases were included if children were &amp;lt;17 years old and hospitalized for COVID-19 (excluding incidental SARS-CoV-2) at one of thirteen sentinel paediatric hospitals. SARS-CoV-2 lineages were classified as “Ancestral”, “pre-Delta” (Alpha, Beta, or Gamma), “Delta”, or “Omicron” based on genetic sequencing or the predominant lineage across Canada at the time of hospitalization. Severe disease was defined as intensive care, ventilatory or hemodynamic support requirements, organ system complications, or death. Results We identified 1357 children hospitalized with COVID-19, including 254 (18.7%) ancestral, 105 (7.7%) pre-Delta, 175 (12.9%) Delta, and 823 (60.6%) Omicron (Table). Median age at hospitalization was highest for Delta (3.0 years, interquartile range 0.2–11.1) and lowest for Omicron (1.3 years, interquartile range 0.3–5.4; p&amp;lt;0.001). The proportion of children with comorbid conditions did not differ significantly by lineage, ranging from 44.9% (ancestral) to 54.3% (Delta, p=0.149). COVID-19 vaccination (≥1 doses) was received by &amp;lt;5 pre-Delta cases (&amp;lt;4.8%), six Delta cases (3.4%), and 98 Omicron cases (11.9%). Among unvaccinated patients (n=1251), severe COVID-19 was most common among Delta lineages (34.3%) versus other lineages (24.0% ancestral, 22.3 pre-Delta, 24.8% Omicron; p=0.049). Conclusion Our results show more children were hospitalized during Omicron waves than all other waves combined, though Delta was relatively more severe. These findings underscore the substantial burden of Omicron in children. Potential competing interests Jesse Papenburg received consultant fees/honoraria from Astra-Zeneca, Merck, and Seegene, and is site PI for industry trials by Astra-Zeneca, MedImmune, Merck, and Sanofi (all outside current work). Rupeena Purewal is a consultant for Verity Pharmaceuticals. Manish Sadarangani has been an investigator on projects funded by GlaxoSmithKline, Merck, Moderna, Pfizer, Sanofi-Pasteur, Seqirus, Symvivo, and VBI Vaccines (all outside current work). Fatima Kakkar received salary support from the FRQS Chercheur Boursieurs Program, and honoraria from the Association des Pédiatres du Québec. Shaun Morris has received honoraria for lectures from GlaxoSmithKline and was a member of ad hoc advisory boards for Pfizer Canada and Sanofi Pasteur (all outside current work). No other competing interests are declared.

Outcomes of immunocompromised children hospitalized for Influenza, 2010-2021, the Canadian Immunization Monitoring Program Active (IMPACT)

ObjectivesTo evaluate immunocompromising conditions and subgroups of immunocompromise as risk factors for severe outcomes among children admitted for influenza. MethodsWe performed active surveillance for laboratory-confirmed influenza hospitalizations among children ≤16 years old at the 12 Canadian Immunization Monitoring Program Active hospitals, during 2010–2021. Logistic regression analyses were used to compare outcomes between immunocompromised and non-immunocompromised children, and for different subgroups of immunocompromise. The primary outcome was intensive care unit (ICU) admission; the secondary outcomes were mechanical ventilation and death. ResultsAmong 8982 children, 892 (9.9%) were immunocompromised; these patients were older (median, 5.6 (IQR, 3.1–10.0) vs. 2.4 (1–6) years; p < 0.001) than non-immunocompromised children, had a similar frequency of comorbidities, excluding immunocompromise and/or malignancy (38% (340/892) vs. 40% (3272/8090); p 0.2), but fewer respiratory symptoms, such as respiratory distress (20% (177/892) vs. 42% (3424/8090), p < 0.001).In multivariable analyses, immunocompromise (adjusted odds ratio (aOR), 0.19; 95% CI, 0.14–0.25) and its subcategories immunodeficiency (aOR, 0.16; 95% CI, 0.10–0.23), immunosuppression (aOR, 0.17; 95% CI, 0.12–0.23), chemotherapy (aOR, 0.07; 95% CI, 0.03–0.13), and solid organ transplantation (aOR, 0.17; 95% CI, 0.06–0.37) were associated with decreased probability of ICU admission in children admitted for influenza. Immunocompromise was also associated with a decreased probability of mechanical ventilation (aOR, 0.26; 95% CI, 0.16–0.38) or death (aOR, 0.22; 95% CI, 0.03–0.72). ConclusionImmunocompromised children are overrepresented among hospitalizations for influenza, but have a decreased probability of ICU admission, mechanical ventilation, and mortality following admission. Admission bias precludes generalizability beyond the hospital setting.

57 Update of IMPACT Invasive Meningococcal Surveillance, 2016-2020

Abstract Background Meningococcal conjugate vaccine (MCV) programs in Canada began in 2002. Objectives This study examines the most recent surveillance data to describe the current Canadian epidemiology of invasive meningococcal disease (IMD) and the effect of MCV programs, especially on age and serogroup distribution. Design/Methods Active metropolitan area surveillance for hospitalization of adults and children due to IMD, which was defined as a clinical infection with Neisseria meningitidis isolated or detected by molecular methods or culture from a sterile body site. The study was conducted via the 12 centres of the Canadian Immunization Monitoring Program, Active (IMPACT) network from January 1, 2016 – December 31, 2020. Results During 2016-2020, a total of 105 pediatric (&amp;lt;20 years of age) and 145 adult IMD cases occurred. Serogroup B accounted for the greatest proportion of pediatric cases (N=58, 55.2%), followed by W (n=19, 18.1%) and Y (n=9, 8.6%) and C (n=2, 1.9%). Among adults, serogroup W accounted for the majority of cases (n=55, 38.0%), followed by Y (n=41, 28.3%), B (n=33, 22.8%) and C (n=7, 4.8%). The age distribution for serogroups covered by MCV programs has shifted to adults. The median age was 24.2 years (33.4 mean). Whereas the median age of serogroup B cases was 7.7 years (19.4 years mean) with 63.7% of cases occurring in children &amp;lt; 19 years of age and 46.2% in children 0-4 years of age. A total of 20 people died from meningococcal infections in 2016–2020. Five deaths were in children, four from serogroup B and one from serogroup W. Fifteen deaths were in adults, one from serogroup B, eight from serogroup W, three from serogroup Y, and three from Non-typeable/Other/Unknown serogroups. Conclusion Serogroup B, which is not covered by MCV programs, still accounts for the majority of pediatric IMD. Serogroup C has been controlled and rarely causes pediatric infection. With the implementation of MCV programs in children and adolescents, the median and mean age at infection has increased across all serogroups, except serogroup B. Serogroup W is still causing IMD among pediatric age groups.

Kawasaki disease following immunization reported to the Canadian Immunization Monitoring Program ACTive (IMPACT) from 2013 to 2018

ABSTRACT Kawasaki disease (KD) is an acute systemic vasculitis primarily affecting children younger than 5 y of age that has been reported as an adverse event following immunization (AEFI). The Canadian Immunization Monitoring Program ACTive (IMPACT) conducts active surveillance for KD following immunization across Canada. We characterized KD cases reported to IMPACT between 2013 and 2018. Cases admitted to an IMPACT hospital with a physician diagnosis of complete or incomplete KD with onset 0–42 d following vaccination were reviewed. Cases meeting the Brighton Collaboration case definition (BCCD) levels of diagnostic certainty levels 1 a/b, 2a/b or 3a-e were defined as KD cases. Demographic and vaccination characteristics were compared between KD cases and non-cases. Of 84 cases reviewed, 58 met the BCCD: 47 (81%) cases met level 1a (Complete KD), 8 (14%) met level 1b (Incomplete KD), 2 (3%) met level 2a, and 1 (2%) met level 2c (Probable KD). Median age at admission was 13 months (interquartile range 7–26 months). A median of 9.5 cases were reported per year (range 4–14). Thirty-one (53%) KD cases were temporally associated with diphtheria-tetanus acellular pertussis containing vaccinations, followed by 21 (36%) cases with pneumococcal conjugate vaccines. Symptom onset was 0–14 d after vaccination in 32 (55%) cases. Echocardiogram results were available for 43 (74%) cases with 22 reported as abnormal. Age, sex, interval to symptom onset, and vaccines received were similar between KD cases and non-cases. No safety signals were detected in these data.

Vaccine effectiveness of the 7-valent and 13-valent pneumococcal conjugate vaccines in Canada: An IMPACT study

We used an indirect cohort analysis in children under 5 years-old from 2002 to 2018 to examine vaccine effectiveness (VE) of the 7-valent pneumococcal conjugate vaccine (PCV) (3 + 1 doses in most regions) and the 13-valent PCV (2 + 1 doses in all regions) against invasive pneumococcal disease (IPD) caused by vaccine serotypes in children in Canada. Cases were identified from the Canadian Immunization Monitoring Program ACTive (IMPACT), a national active surveillance network of 12 tertiary care pediatric hospitals that represent about 90% of tertiary care hospital beds in Canada. There were 1477 children evaluated for PCV7 VE and 489 for PCV13 VE. PCV7 VE in children with vaccination up to date for their age was 96% (95% CI: 67–99%) after a single dose and 95% (95% CI: 92–97%) after ≥2 doses. The VE was 91% (95% CI: 85–94%) in children who had received doses but were not up to date for their age. PCV13 VE in children with vaccinations up to date for their age was 55% (95% CI: 28–72%) after ≥2 doses. The PCV13-vaccine serotypes causing breakthrough IPD in children up to date for their age with 2+ doses of PCV13 were 3 (13/27, 48.2%),19A (11/27, 40.7%), and 19F (3/27, 11.1%). When serotype 3 and 19A were excluded, the VE of PCV13 against the remaining vaccine serotypes was 89% (95% CI: 64–97%) in children with ≥2 doses. The lower VE of PCV13 may be due to lower effectiveness against serotypes 3 and 19A, which could be influenced by the change in dosing schedule from 4 to 3 total doses with the introduction of PCV13, combined with vaccine uptake of 80%. However, PCV13 still provides the benefit of protection against more serotypes than PCV7, and good VE against all serotypes except 3 and 19A.

Clinical Presentations and Outcomes of Children in Canada With Recurrent Invasive Pneumococcal Disease From the IMPACT Surveillance Network.

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.

1188. The Effect Of The COVID-19 Pandemic On Influenza-Related Hospitalization, Intensive Care Admission And Mortality In Canadian Children

BackgroundThe COVID-19 pandemic resulted in unprecedented implementation of wide-ranging public health measures globally. During the pandemic, dramatic decreases in seasonal influenza virus detection have been reported worldwide. Information on pediatric influenza-related hospitalizations is limited. We describe influenza-related hospitalization in Canadian children during the 2020/2021 influenza season compared to ten previous seasons.MethodsData on influenza-related hospitalizations, intensive care unit (ICU) admissions and in-hospital deaths in children across Canada were obtained from the Canadian Immunization Monitoring Program, ACTive (IMPACT). This national surveillance initiative comprises 90% of all tertiary care pediatric beds in Canada. The total study period included eleven influenza seasons from September 2010 to April 2021 inclusive. Time series modelling was used to compare trends in influenza-related hospitalizations during the 2020/2021 season (September 2020 to April 2021 inclusive) with the ten previous seasons.ResultsDuring the 2020/2021 influenza season there were no pediatric influenza infection-related hospitalizations. This was a significant decrease compared to the predicted total influenza-related hospitalizations for this period (p< 0.001). No pediatric ICU admission or deaths were reported for the 2020/2021 influenza season.ConclusionWe show complete absence of influenza infection-related hospitalization in children in Canada during the 2020/2021 season. This significant decrease is likely related in large part to non-pharmacological public health interventions implemented during the COVID-19 pandemic, although the potential role of viral interference is unknown. Our findings suggest measures such as use of facemasks, hand-washing, distancing and school closures may be beneficial for influenza control and mitigation of future influenza epidemics.Disclosures Helen E. Groves, PhD, MBBCh BAO, Abbvie (Other Financial or Material Support, Dr. Groves reports personal fees from Honoraria received from Abbvie for education meeting presentation, not relevant to the submitted work.) Jesse Papenburg, MD, AbbVie (Grant/Research Support, Other Financial or Material Support, Personal fees)Medimmune (Grant/Research Support)Sanofi Pasteur (Grant/Research Support)Seegene (Grant/Research Support, Other Financial or Material Support, Personal fees) Manish Sadarangani, BM BCh, DPhil, GlaxoSmithKline (Grant/Research Support)Merck (Grant/Research Support)Pfizer (Grant/Research Support)Sanofi Pasteur (Grant/Research Support)Seqirus (Grant/Research Support)Symvivo (Grant/Research Support)VBI Vaccines (Research Grant or Support) Shaun Morris, MD, MPH, DTM&H, FRCPC, FAAP, GSK (Speaker’s Bureau)Pfizer (Advisor or Review Panel member)Pfizer (Grant/Research Support)

Antiviral Use in Canadian Children Hospitalized for Influenza.

Antivirals are recommended for children hospitalized with influenza but are underutilized. We describe antiviral prescribing during influenza admissions in Canadian pediatric centers and identify factors associated with antiviral use. We performed active surveillance for laboratory-confirmed influenza hospitalizations among children ≤16 years old at the 12 Canadian Immunization Monitoring Program Active hospitals, from 2010-2011 to 2018-2019. Logistic regression analyses were used to identify factors associated with antiviral use. Among 7545 patients, 57.4% were male; median age was 3 years (interquartile range: 1.1-6.3). Overall, 41.3% received antiviral agents; 72.8% received antibiotics. Antiviral use varied across sites (range, 10.2% to 81.1%) and influenza season (range, 19.9% to 59.6%) and was more frequent in children with ≥1 chronic health condition (52.7% vs 36.7%; P < .001). On multivariable analysis, factors associated with antiviral use included older age (adjusted odds ratio [aOR] 1.04 [95% confidence interval (CI), 1.02-1.05]), more recent season (highest aOR 9.18 [95% CI, 6.70-12.57] for 2018-2019), admission during peak influenza period (aOR 1.37 [95% CI, 1.19-1.58]), availability of local treatment guideline (aOR 1.54 [95% CI, 1.17-2.02]), timing of laboratory confirmation (highest aOR 2.67 [95% CI, 1.97-3.61] for result available before admission), presence of chronic health conditions (highest aOR 4.81 [95% CI, 3.61-6.40] for cancer), radiographically confirmed pneumonia (aOR 1.39 [95% CI, 1.20-1.60]), antibiotic treatment (aOR 1.51 [95% CI, 1.30-1.76]), respiratory support (1.57 [95% CI, 1.19-2.08]), and ICU admission (aOR 3.62 [95% CI, 2.88-4.56]). Influenza antiviral agents were underused in Canadian pediatric hospitals, including among children with high-risk chronic health conditions. Prescribing varied considerably across sites, increased over time, and was associated with patient and hospital-level characteristics. Multifaceted hospital-based interventions are warranted to strengthen adherence to influenza treatment guidelines and antimicrobial stewardship practices.

Active surveillance of acute paediatric hospitalisations demonstrates the impact of vaccination programmes and informs vaccine policy in Canada and Australia.

Sentinel surveillance of acute hospitalisations in response to infectious disease emergencies such as the 2009 influenza A(H1N1)pdm09 pandemic is well described, but recognition of its potential to supplement routine public health surveillance and provide scalability for emergency responses has been limited. We summarise the achievements of two national paediatric hospital surveillance networks relevant to vaccine programmes and emerging infectious diseases in Canada (Canadian Immunization Monitoring Program Active; IMPACT from 1991) and Australia (Paediatric Active Enhanced Disease Surveillance; PAEDS from 2007) and discuss opportunities and challenges in applying their model to other contexts. Both networks were established to enhance capacity to measure vaccine preventable disease burden, vaccine programme impact, and safety, with their scope occasionally being increased with emerging infectious diseases’ surveillance. Their active surveillance has increased data accuracy and utility for syndromic conditions (e.g. encephalitis), pathogen-specific diseases (e.g. pertussis, rotavirus, influenza), and adverse events following immunisation (e.g. febrile seizure), enabled correlation of biological specimens with clinical context and supported responses to emerging infections (e.g. pandemic influenza, parechovirus, COVID-19). The demonstrated long-term value of continuous, rather than incident-related, operation of these networks in strengthening routine surveillance, bridging research gaps, and providing scalable public health response, supports their applicability to other countries.

Review of pediatric encephalitis and encephalopathy cases following immunization reported to the Canadian Immunization Monitoring Program Active (IMPACT) from 1992 to 2012

BackgroundNeurological adverse events following immunization (AEFI) remain poorly characterized. Our objective was to describe pediatric acute and chronic encephalopathy and encephalitis cases following immunization reported via active sentinel surveillance from 1992 to 2012. MethodsThis case series provides a descriptive analysis of encephalopathy/encephalitis admissions reported to the Canadian Immunization Monitoring Program ACTive (IMPACT). Acute cases were reported if symptom onset (seizures, decreased level of consciousness, change in mental status) occurred 0–7 days after tetanus or pertussis-containing vaccines, 0–15 days after other inactivated vaccines, or 5–30 days after live vaccines. Chronic cases of subacute sclerosing panencephalitis or subacute progressive rubella encephalitis were reported at any interval after vaccination. Clinical data were examined to identify possible causes for encephalopathy/encephalitis other than vaccination. ResultsSixty-one cases of encephalopathy/encephalitis following immunization were reported to IMPACT over 21 years; 57 (93.4%) were classified as acute and 4 (6.6%) were chronic cases of subacute sclerosing panencephalitis. Most patients (73.8%) were previously healthy and immunocompetent. The vaccines most frequently administered prior to presentation were diphtheria-tetanus-pertussis, measles-mumps-rubella, and influenza. At discharge, 38 patients (62.3%) had normal neurological status or were expected to recover. Forty patients (70.2%) with acute encephalopathy/encephalitis had a more likely alternate etiology besides vaccination based on neuroimaging, symptoms suggestive of infection, laboratory-confirmed non-vaccine-related infection, or clinical diagnosis. No cases of encephalitis were causally associated with pertussis or influenza vaccines. Two patients (50%) with subacute sclerosing panencephalitis had known wild-type measles infection prior to immunization. Three deaths were reported during hospitalization (4.9%); all were acute encephalitis/encephalopathy cases and none were confirmed to be vaccine-related. ConclusionsEncephalopathy/encephalitis following immunization remains a rare but serious adverse event. Most cases had another more likely etiology than vaccination. Continued monitoring and analysis of AEFI is paramount to ensure the safety of immunization programs.

Estimated susceptibility of Canadian meningococcal B isolates to a meningococcal serogroup B vaccine (MenB-FHbp)

BackgroundInvasive meningococcal disease caused by Neisseria meningitidis serogroup B (MenB) remains a health risk in Canada and globally. Two MenB vaccines are now approved for use. An understanding of the genotype of Canadian strains and the potential strain coverage conferred by the MenB-FHbp vaccine is needed to inform immunization policies. MethodsSerogroup B Neisseria meningitidis strains responsible for meningococcal disease in Canada from 2006 to 2012 were collected as part of the Canadian Immunization Monitoring Program Active surveillance network. Genotypic analysis was done on MenB isolates from 2006 to 2012 with determination of fHbp surface expression for a subset of isolates: those occurring from 2010 to 2012. ResultsTwo clonal complexes (cc269 and cc41/44) were observed in 68.8% of the 276 isolates. A total of 50 different fHbp peptides were identified among isolates from 2006 to 2012. Surface expression of fHbp was detected on 95% of MenB isolates from 2010 to 2012 and 91% of isolates expressed fHbp at levels that are predicted to be susceptible to the bactericidal immune response elicited by the MenB-FHbp vaccine. Some regional differences were observed, particularly in isolates from British Columbia and Quebec. ConclusionThe majority of MenB isolates responsible for meningococcal disease in Canada expressed fHbp at levels predicted to be sufficient for complement mediated bactericidal activity in the presence of MenB-FHbp induced serum antibodies.

An Introduction of the Active Vaccine Safety Surveillance System in Foreign Countries

Vaccines require higher safety standards than most other medicinal products because they are given to healthy individuals, including infants, children, and elderly. Despite various activities by national agencies, public concern about vaccine safety often arises. Post-marketing activities for vaccine safety can be broadly classified into passive and active surveillances. Many countries as well as Korea operate passive vaccine safety surveillance systems that report adverse events related to vaccines. However, the active surveillance systems operate only in several countries, such as the United States of America (USA), Europe, Canada and Australia. In the US, Vaccine Safety Datalink (VSD) and Post-Licensure Rapid Immunization Safety Monitoring (PRISM) were developed in 1990 and 2009 respectively for monitoring vaccine actively. In the case of Europe, the Vaccine Adverse Event Surveillance and Communication (VAESCO) consortium was launched in 2008. After the end of VAESCO, the Accelerated Development of VAccine beNefit-risk Collaboration in Europe (ADVANCE) was organized to establish a vaccine benefit-risk monitoring framework in 2013. Canada has been operating a vaccine active monitoring system known as the Canadian Immunization Monitoring Program, ACTive (IMPACT) since 1991. The objective of this review was to describe and compare background, databases, and analysis systems of various vaccine active surveillance systems in the US, Europe, and Canada. We described the examples of studies on the safety of influenza A (H1N1) vaccines carried out in each system. This review could help provide directions for the future development of the ideal active vaccine safety surveillance system in Korea. Key words: Vaccine, Safety, Active vaccine surveillance system, Database, H1N1 influenza virus vaccine

VARICELLA-RELATED HOSPITALIZATIONS IN IMPACT CENTERS AFTER INTRODUCTION OF 1- AND 2-DOSE VARICELLA VACCINATION PROGRAMS BETWEEN 2000 AND 2015

Abstract BACKGROUND The Canadian Immunization Monitoring Program ACTive (IMPACT) conducts active surveillance for varicella-related hospitalizations in 12 paediatric tertiary care centres, starting Apr 1999. OBJECTIVES This study was to determine the hospitalization trends in relation to vaccine program introduction in the provinces, between 2000 and 2015. DESIGN/METHODS Demographic data of varicella cases from the 12 IMPACT centers were analysed. The cases were subdivided into three groups (A, B and C), combining provinces with approximately the same time periods at introduction of 1-dose and 2-dose vaccination programs (see results). RESULTS The mean number of hospitalizations per year declined during the 1-dose and 2-dose eras in each group of provinces, as follows: CONCLUSION Varicella hospitalizations declined by 63–77% but reached a plateau during the 1-dose vaccine era. There was a further decline to 81–89% of baseline in the two groups which instituted 2-dose vaccine programs in 2011–12, but too early to document any further decline in Group C, the provinces which initiated 2-dose programs in 2014–16. Introduction of 2-dose programs appear to have provided further benefit, after 1-dose programs in Canada.