Paediatric inflammatory multisystem syndrome in Canada: population-based surveillance and role of SARS-CoV-2 linkage.

BACKGROUND: Paediatric inflammatory multisystem syndrome (PIMS) is a rare condition temporally associated with SARS-CoV-2 infection. Using national surveillance data, we compare presenting features and outcomes among children hospitalized with PIMS by SARS-CoV-2 linkage, and identify risk factors for intensive care (ICU). METHODS: Cases were reported to the Canadian Paediatric Surveillance Program by a network of >2800 pediatricians between March 2020 and May 2021. Patients with positive versus negative SARS-CoV-2 linkages were compared, with positive linkage defined as any positive molecular or serologic test or close contact with confirmed COVID-19. ICU risk factors were identified with multivariable modified Poisson regression. RESULTS: We identified 406 children hospitalized with PIMS, including 49.8% with positive SARS-CoV-2 linkages, 26.1% with negative linkages, and 24.1% with unknown linkages. The median age was 5.4 years (IQR 2.5-9.8), 60% were male, and 83% had no comorbidities. Compared to cases with negative linkages, children with positive linkages experienced more cardiac involvement (58.8% vs. 37.4%; p < 0.001), gastrointestinal symptoms (88.6% vs. 63.2%; p < 0.001), and shock (60.9% vs. 16.0%; p < 0.001). Children aged ≥6 years and those with positive linkages were more likely to require ICU. CONCLUSIONS: Although rare, 30% of PIMS hospitalizations required ICU or respiratory/hemodynamic support, particularly those with positive SARS-CoV-2 linkages. IMPACT: We describe 406 children hospitalized with paediatric inflammatory multisystem syndrome (PIMS) using nationwide surveillance data, the largest study of PIMS in Canada to date. Our surveillance case definition of PIMS did not require a history of SARS-CoV-2 exposure, and we therefore describe associations of SARS-CoV-2 linkages on clinical features and outcomes of children with PIMS. Children with positive SARS-CoV-2 linkages were older, had more gastrointestinal and cardiac involvement, and hyperinflammatory laboratory picture. Although PIMS is rare, one-third required admission to intensive care, with the greatest risk amongst those aged ≥6 years and those with a SARS-CoV-2 linkage.

Knowledge of Congenital CMV, Risk Behaviours for CMV Acquisition, and Acceptance of an Educational Infographic Among Postpartum Women: A Pilot Study.

Congenital cytomegalovirus (cCMV) infection in the newborn can present with sensorineural hearing loss and microcephaly. The objectives of this study were to determine baseline knowledge of cCMV and the acceptability of an infographic about cCMV among a group of postpartum women. Participants completed a questionnaire assessing their perceptions of an infographic as well as their knowledge and risk behaviours for acquisition of CMV. Of all 140 respondents, 119 (85%) had no prior knowledge of cCMV, and all 12 women (8.6%) who viewed the infographic indicated that it was helpful. Our study also demonstrated that passive dissemination of an infographic in clinics results in limited viewership.

Characteristics of children admitted to hospital with acute SARS-CoV-2 infection in Canada in 2020.

BACKGROUND: Risk factors for severe outcomes of SARS-CoV-2 infection are not well established in children. We sought to describe pediatric hospital admissions associated with SARS-CoV-2 infection in Canada and identify risk factors for more severe disease. METHODS: We conducted a national prospective study using the infrastructure of the Canadian Paediatric Surveillance Program (CPSP). Cases involving children who were admitted to hospital with microbiologically confirmed SARS-CoV-2 infection were reported from Apr. 8 to Dec. 31 2020, through weekly online questionnaires distributed to the CPSP network of more than 2800 pediatricians. We categorized hospital admissions as related to COVID-19, incidental, or for social or infection control reasons and determined risk factors for disease severity in hospital. RESULTS: Among 264 hospital admissions involving children with SARS-CoV-2 infection during the 9-month study period, 150 (56.8%) admissions were related to COVID-19 and 100 (37.9%) were incidental infections (admissions for other reasons and found to be positive for SARS-CoV-2 on screening). Infants (37.3%) and adolescents (29.6%) represented most cases. Among hospital admissions related to COVID-19, 52 (34.7%) had critical disease, 42 (28.0%) of whom required any form of respiratory or hemodynamic support, and 59 (39.3%) had at least 1 underlying comorbidity. Children with obesity, chronic neurologic conditions or chronic lung disease other than asthma were more likely to have severe or critical COVID-19. INTERPRETATION: Among children who were admitted to hospital with SARS-CoV-2 infection in Canada during the early COVID-19 pandemic period, incidental SARS-CoV-2 infection was common. In children admitted with acute COVID-19, obesity and neurologic and respiratory comorbidities were associated with more severe disease.

Results from the Canadian Nosocomial Infection Surveillance Program for detection of carbapenemase-producing Acinetobacter spp. in Canadian hospitals, 2010-16.

Objectives: Globally there is an increased prevalence of carbapenem-resistant Acinetobacter spp. (CRAs) and carbapenemase-producing Acinetobacter spp. (CPAs) in the hospital setting. This increase prompted the Canadian Nosocomial Infection Surveillance Program (CNISP) to conduct surveillance of CRA colonizations and infections identified from patients in CNISP-participating hospitals between 2010 and 2016. Methods: Participating acute care facilities across Canada submitted CRAs from 1 January 2010 to 31 December 2016. Patient data were collected from medical records using a standardized questionnaire. WGS was conducted on all CRAs and data underwent single nucleotide variant analysis, resistance gene detection and MLST. Results: The 7 year incidence rate of CRA was 0.02 per 10 000 patient days and 0.015 per 1000 admissions, with no significant increase observed over the surveillance period (P > 0.73). Ninety-four CRA isolates were collected from 58 hospitals, of which 93 (98.9%) were CPA. Carbapenemase OXA-235 group (48.4%) was the most common due to two separate clusters, followed by the OXA-23 group (41.9%). Patients with a travel history were associated with 38.8% of CRA cases. The all-cause 30 day mortality rate for infected cases was 24.4 per 100 CRA cases. Colistin was the most active antimicrobial agent (95.8% susceptibility). Conclusions: CRA remains uncommon in Canadian hospitals and the incidence did not increase from 2010 to 2016. Almost half of the cases were from two clusters harbouring OXA-235-group enzymes. Previous medical treatment during travel outside of Canada was common.

Results from the Canadian Nosocomial Infection Surveillance Program on Carbapenemase-Producing Enterobacteriaceae, 2010 to 2014.

Carbapenemase-producing Enterobacteriaceae (CPE) are increasing globally; here we report on the investigation of CPE in Canada over a 5-year period. Participating acute care facilities across Canada submitted carbapenem-nonsusceptible Enterobacteriaceae from 1 January 2010 to 31 December 2014 to the National Microbiology Laboratory. All CPE were characterized by antimicrobial susceptibilities, pulsed-field gel electrophoresis, multilocus sequence typing, and plasmid restriction fragment length polymorphism analysis and had patient data collected using a standard questionnaire. The 5-year incidence rate of CPE was 0.09 per 10,000 patient days and 0.07 per 1,000 admissions. There were a total of 261 CPE isolated from 238 patients in 58 hospitals during the study period. blaKPC-3 (64.8%) and blaNDM-1 (17.6%) represented the highest proportion of carbapenemase genes detected in Canadian isolates. Patients who had a history of medical attention during international travel accounted for 21% of CPE cases. The hospital 30-day all-cause mortality rate for the 5-year surveillance period was 17.1 per 100 CPE cases. No significant increase in the occurrence of CPE was observed from 2010 to 2014. Nosocomial transmission of CPE, as well as international health care, is driving its persistence within Canada.

Caractéristiques des hospitalisations au Canada d'enfants ayant contracté une infection aiguë par le SRAS-CoV-2 en 2020.

CONTEXTE: Les facteurs de risque de complications graves de l'infection par le SRAS-CoV-2 n'ont pas été bien établis chez les enfants. Nous avons voulu décrire les hospitalisations pédiatriques associées au SRAS-CoV-2 au Canada et identifier les facteurs de risque de maladie grave. MÉTHODES: Nous avons procédé à une étude prospective nationale en utilisant l'infrastructure du Programme canadien de surveillance pédiatrique (PCSP). Les hospitalisations d'enfants ayant contracté une infection par le SRAS-CoV-2 confirmée en laboratoire de microbiologie ont été rapportées du 8 avril au 31 décembre 2020 au moyen de questionnaires hebdomadaires en ligne distribués au réseau du PCSP, qui compte plus de 2800 pédiatres. Nous avons catégorisé les hospitalisations comme suit : liées à la COVID-19, infections découvertes fortuitement, ou hospitalisations pour des raisons sociales ou de contrôle des infections, et dégagé les facteurs de risque associés à la gravité de la maladie chez les patients hospitalisés. RÉSULTATS: Sur les 264 hospitalisations d'enfants ayant contracté le SRAS-CoV-2 au cours de la période de l'étude de 9 mois, 150 (56,8 %) ont été associées à la COVID-19 et 100 (37,9 %) étaient des cas découverts fortuitement (admission pour d'autres raisons et découverte fortuite du SRAS-CoV-2 par dépistage positif). Les nourrissons (37,3 %) et les adolescents (29,6 %) représentaient la majorité des cas. Parmi les hospitalisations liées à la COVID-19, 52 patients (34,7 %) étaient atteints d'une forme grave de la maladie, dont 42 (28,0 % des cas liés à la COVID-19) ont eu besoin d'une forme d'assistance respiratoire ou hémodynamique, et 59 (39,3 %) présentaient au moins 1 comorbidité sous-jacente. Les enfants atteints d'obésité, de maladies neurologiques chroniques ou de maladies pulmonaires chroniques, à l'exclusion de l'asthme, étaient plus susceptibles de présenter une forme grave ou critique de la COVID-19. INTERPRÉTATION: Parmi les enfants hospitalisés au Canada chez lesquels on a diagnostiqué une infection par le SRAS-CoV-2 au début de la pandémie de COVID-19, la découverte fortuite du SRAS-CoV-2 a été fréquente. Chez les enfants hospitalisés pour une COVID-19 aiguë, l'obésité et les comorbidités neurologiques et respiratoires ont été associées à une gravité accrue.

Pediatric Staphylococcus aureus Infections: Impact of Methicillin Resistance at a Canadian Center.

OBJECTIVES: Methicillin-resistant Staphylococcus aureus (MRSA) causes a wide spectrum of potentially serious infections in children. This study describes the evolving experience with S. aureus infections at a Canadian tertiary pediatric care center serving a wide geographic area. DESIGN: In this two-component study, a retrospective review of infection control databases for MRSA infection was conducted, along with a prospective component for 1 year during which all community-onset S. aureus infections were identified. Cases with methicillin resistance and susceptibility were compared. RESULTS: Review of infection control database records showed 239 unique infections, with steady increases over time. Common pulsed-field gel electrophoresis types included Canadian MRSA-7 and Canadian MRSA-10. During the 1-year prospective component, 210 clinical infections were identified, with MRSA isolated in 41%. Patients with MRSA were significantly younger than those with methicillin-susceptible isolates (4.9 vs 7.7 years, P < 0.001). The most common presentations were soft tissue infections in the emergency department, with a degree of inappropriate antimicrobial use. CONCLUSIONS: MRSA contributed to a significant proportion of S. aureus infections at a large Canadian tertiary care center. Ample opportunities exist to develop stewardship protocols, especially for the management of soft tissue infections in outpatients.

Prevalence of antimicrobial use in a network of Canadian hospitals in 2002 and 2009.

BACKGROUND: Increasing antimicrobial resistance has been identified as an important global health threat. Antimicrobial use is a major driver of resistance, especially in the hospital sector. Understanding the extent and type of antimicrobial use in Canadian hospitals will aid in developing national antimicrobial stewardship priorities. METHODS: In 2002 and 2009, as part of one-day prevalence surveys to quantify hospital-acquired infections in Canadian Nosocomial Infection Surveillance Program hospitals, data were collected on the use of systemic antimicrobial agents in all patients in participating hospitals. Specific agents in use (other than antiviral and antiparasitic agents) on the survey day and patient demographic information were collected. RESULTS: In 2002, 2460 of 6747 patients (36.5%) in 28 hospitals were receiving antimicrobial therapy. In 2009, 3989 of 9953 (40.1%) patients in 44 hospitals were receiving antimicrobial therapy (P<0.001). Significantly increased use was observed in central Canada (37.4% to 40.8%) and western Canada (36.9% to 41.1%) but not in eastern Canada (32.9% to 34.1%). In 2009, antimicrobial use was most common on solid organ transplant units (71.0% of patients), intensive care units (68.3%) and hematology/oncology units (65.9%). Compared with 2002, there was a significant decrease in use of first-and second-generation cephalosporins, and significant increases in use of carbapenems, antifungal agents and vancomycin in 2009. Piperacillin-tazobactam, as a proportion of all penicillins, increased from 20% in 2002 to 42.8% in 2009 (P<0.001). There was a significant increase in simultaneous use of >1 agent, from 12.0% of patients in 2002 to 37.7% in 2009. CONCLUSION: From 2002 to 2009, the prevalence of antimicrobial agent use in Canadian Nosocomial Infection Surveillance Program hospitals significantly increased; additionally, increased use of broad-spectrum agents and a marked increase in simultaneous use of multiple agents were observed.

HISTORIQUE: La résistance antimicrobienne croissante est une menace importante pour la santé dans le monde. L'utilisation d'antimicrobiens est un moteur de résistance majeur, particulièrement dans le milieu hospitalier. Il faut comprendre la portée et le type d'utilisation des antimicrobiens dans les hôpitaux canadiens pour établir les priorités nationales en matière de gouvernance antimicrobienne. MÉTHODOLOGIE: En 2002 et 2009, dans le cadre de sondages de prévalence d'une journée visant à quantifier les infections nosocomiales dans les hôpitaux du Programme canadien de surveillance des infections nosocomiales, les chercheurs ont colligé des données sur l'utilisation des antimicrobiens systémiques par tous les patients des hôpitaux participants. Le jour du sondage, ils ont recueilli les agents précis utilisés (à part les antiviraux et les antiparasitaires) et l'information démographique relative aux patients. RÉSULTATS: En 2002, 2 460 des 6 747 patients (36,5 %) de 28 hôpitaux recevaient un traitement antimicrobien. En 2009, 3 989 des 9 953 patients (40,1 %) de 44 hôpitaux recevaient un tel traitement (P<0,001). L'utilisation avait beaucoup augmenté au centre du Canada (37,4 % à 40,8 %) et dans l'Ouest canadien (36,9 % à 41,1 %), mais pas dans l'Est canadien (32,9 % à 34,1 %). En 2009, l'utilisation d'antimicrobiens était plus courante dans les unités de transplantation d'organes pleins (71,0 % des patients), les unités de soins intensifs (68,3 %) et les unités d'hématologie-oncologie (65,9 %). Par rapport à 2002, on constatait en 2009 une diminution importante des céphalosporines de première et seconde générations et des augmentations marquées de carbapénèmes, d'antifongiques et de vancomycine. L'utilisation de piperacilline-tazobactam, en proportion de toutes les pénicillines, est passée de 20 % en 2002 à 42,8 % en 2009 (P<0,001). L'utilisation simultanée de plus d'un agent a également connu une hausse importante, passant de 12,0 % des patients en 2002 à 37,7 % en 2009. CONCLUSION: De 2002 à 2009, la prévalence d'utilisation d'antimicrobiens dans les hôpitaux du Programme canadien de surveillance des infections nosocomiales a considérablement augmenté. De plus, les chercheurs ont constaté une augmentation marquée d'agents à large spectre et d'utilisation simultanée de multiples agents.

Severe combined immunodeficiency (SCID) in Canadian children: a national surveillance study.

PURPOSE: Severe Combined Immune Deficiency (SCID) is universally fatal unless treated with hematopoietic stem cell transplantation (HSCT). Following the identification of disseminated Bacille Calmette-Guérin (BCG) infections in Canadian First Nations, Métis and Inuit (FNMI) children with unrecognized primary immune deficiencies, a national surveillance study was initiated in order to determine the incidence, diagnosis, treatment and outcome of children with SCID in Canada. METHODS: Canadian pediatricians were asked to complete a monthly reporting form if they had seen a suspected SCID case, from 2004 to 2010, through the Canadian Paediatric Surveillance Program (CPSP). If the case met CPSP SCID criteria, more detailed data, including demographics and clinical information about investigations, treatment and outcome was collected. RESULTS: A total of 40 cases of SCID were confirmed for an estimated incidence of SCID in non-FNMI Canadian children of 1.4 per 100,000 live births (95 % CI 1 to 1.9/100,000). The proportion of SCID cases that were FNMI (17.5 %) was almost three times higher than was expected on the basis of proportion of the pediatric population estimated to be FNMI (6.3 %) resulting in an estimated incidence of 4.4 per 100,000 live births (95 % CI 2.1 to 9.2/100,000) in FNMI Canadian children. The mean age at diagnosis for all SCID cases was 4.2 months (range 1­583 days). There were 12 deaths (30 %; 95 % CI 18­46 %); seven died of confirmed or suspected infections before they could receive an HSCT. CONCLUSIONS: The frequency of SCID cases in FNMI children is higher than in the general Canadian pediatric population. The high mortality rate, due primarily to infection, suggests that early diagnosis by newborn screening followed by HSCT could significantly benefit children with SCID.

A genetic polymorphism of FREM1 is associated with resistance against HIV infection in the Pumwani sex worker cohort.

A subgroup of women enrolled in the Pumwani sex worker cohort remain seronegative and PCR negative for human immunodeficiency virus type 1 despite repeated exposure through high-risk sex work. Studies have shown that polymorphisms of genes involved in antigen presentation and viral restriction factors are associated with resistance to HIV infection. To discover other possible genetic factors underlying this HIV-resistant phenotype, we conducted an exploratory nonbiased, low-resolution, genome-wide single-nucleotide polymorphism (SNP) analysis comparing 60 HIV-resistant women to 48 HIV-infected controls. The SNP minor allele rs1552896, in an intron of FREM1, was significantly associated with the resistant phenotype (P = 1.68 × 10(-5); adjusted P = 2.37 × 10(-4); odds ratio [OR], 9.51; 95% confidence interval [CI], 2.82 to 32.05). We expanded the sample size by genotyping rs1552896 in the Pumwani cohort and comparing 114 HIV-resistant women to 609 HIV-infected controls and confirmed the association (P = 1.7 × 10(-4); OR, 2.67; 95% CI, 1.47 to 4.84). To validate the association in a second cohort, we genotyped 783 women enrolled in a mother-child health study and observed the minor allele of rs1552896 enriched in HIV-uninfected women (n = 488) compared to HIV-infected enrollees (n = 295) (P = 0.036; OR, 1.69; 95% CI, 0.98 to 2.93). Quantitative reverse transcription-PCR showed that FREM1 mRNA was highly expressed in tissues relevant for HIV-1 infection, and immunohistochemical analysis revealed that FREM1 protein is expressed in the ectocervical mucosa of HIV-resistant women. The significant association of rs1552896 with an HIV-resistant phenotype, together with the expression profile of FREM1 in tissues relevant to HIV infection, suggests that FREM1 is a potentially novel candidate gene for resistance to HIV infection.

Cerebrospinal fluid shunt-associated surgical site infection with three-month versus twelve-month surveillance periods in Canadian hospitals.

Cerebrospinal fluid shunt-associated surgical site infection surveillance for 3 months compared to 12 months after surgery captures 83% of cases with no significant differences in patient characteristics, surgery types, or pathogens. A shorter 3-month follow-up can reduce resource use and allow for more timely reporting of healthcare-associated infection rates for hospitals.

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

Importance: Respiratory syncytial virus (RSV) is a leading cause of pediatric hospitalizations. Objective: 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. Design, Setting, and Participants: 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. Main Outcomes and Measures: 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. Results: 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. Conclusions and Relevance: 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.

Antimicrobial use among paediatric inpatients at hospital sites within the Canadian Nosocomial Infection Surveillance Program, 2017/2018.

BACKGROUND: Antimicrobial resistance threatens the ability to successfully prevent and treat infections. While hospital benchmarks regarding antimicrobial use (AMU) have been well documented among adult populations, there is less information from among paediatric inpatients. This study presents benchmark rates of antimicrobial use (AMU) for paediatric inpatients in nine Canadian acute-care hospitals. METHODS: Acute-care hospitals participating in the Canadian Nosocomial Infection Surveillance Program submitted annual AMU data from paediatric inpatients from 2017 and 2018. All systemic antimicrobials were included. Data were available for neonatal intensive care units (NICUs), pediatric ICUs (PICUs), and non-ICU wards. Data were analyzed using days of therapy (DOT) per 1000 patient days (DOT/1000pd). RESULTS: Nine hospitals provided paediatric AMU data. Data from seven NICU and PICU wards were included. Overall AMU was 481 (95% CI 409-554) DOT/1000pd. There was high variability in AMU between hospitals. AMU was higher on PICU wards (784 DOT/1000pd) than on non-ICU (494 DOT/1000pd) or NICU wards (333 DOT/1000pd). On non-ICU wards, the antimicrobials with the highest use were cefazolin (66 DOT/1000pd), ceftriaxone (59 DOT/1000pd) and piperacillin-tazobactam (48 DOT/1000pd). On PICU wards, the antimicrobials with the highest use were ceftriaxone (115 DOT/1000pd), piperacillin-tazobactam (115 DOT/1000pd), and cefazolin (111 DOT/1000pd). On NICU wards, the antimicrobials with the highest use were ampicillin (102 DOT/1000pd), gentamicin/tobramycin (78 DOT/1000pd), and cefotaxime (38 DOT/1000pd). CONCLUSIONS: This study represents the largest collection of antimicrobial use data among hospitalized paediatric inpatients in Canada to date. In 2017/2018, overall AMU was 481 DOT/1000pd. National surveillance of AMU among paediatric inpatients is necessary for establishing benchmarks and informing antimicrobial stewardship efforts.

Resource use and disease severity of children hospitalized for COVID-19 versus multisystem inflammatory syndrome in children (MIS-C) in Canada.

Background: Direct comparisons of paediatric hospitalizations for acute coronavirus disease 2019 (COVID-19) and multisystem inflammatory syndrome in children (MIS-C) can inform health system planning. We describe the absolute and relative hospital burden of acute paediatric COVID-19 and MIS-C in Canada. Methods: This national prospective study was conducted via the Canadian Paediatric Surveillance Program from March 2020-May 2021. Children younger than 18 years old and hospitalized for acute COVID-19 or MIS-C were included in the analysis. Outcomes included supplemental oxygen (low-flow oxygen or high-flow nasal cannula), ventilation (non-invasive or conventional mechanical), vasopressors, paediatric intensive care unit (PICU) admission, or death. Adjusted risk differences (aRD) and 95% confidence intervals (CI) were calculated to identify factors associated with each diagnosis. Results: Overall, we identified 330 children hospitalized for acute COVID-19 (including five deaths) and 208 hospitalized for MIS-C (including zero deaths); PICU admission was required for 49.5% of MIS-C hospitalizations versus 18.2% of acute COVID-19 hospitalizations (aRD 20.3; 95% CI, 9.9-30.8). Resource use differed by age, with children younger than one year hospitalized more often for acute COVID-19 (aRD 43.4% versus MIS-C; 95% CI, 37.7-49.1) and more children 5-11 years hospitalized for MIS-C (aRD 38.9% vs. acute COVID-19; 95% CI, 31.0-46.9). Conclusion: While there were more hospitalizations and deaths from acute paediatric COVID-19, MIS-C cases were more severe, requiring more intensive care and vasopressor support. Our findings suggest that both acute COVID-19 and MIS-C should be considered when assessing the overall burden of severe acute respiratory syndrome coronavirus 2 in hospitalized children.

Molecular characterization of rotavirus isolates from select Canadian pediatric hospitals.

BACKGROUND: We report the first multi-site rotavirus genotype analysis in Canada. Prior to this study, there was a dearth of rotavirus G and P genotyping data in Canada. Publically funded universal rotavirus vaccination in Canada started in 2011 and has been introduced by four provinces to date. Uptake of rotavirus vaccines in Canada prior to 2012 has been very limited. The aim of this study was to describe the genotypes of rotavirus strains circulating in Canada prior to widespread implementation of rotavirus vaccine by genotyping samples collected from selected paediatric hospitals. Secondly we identified rotavirus strains that differed genetically from those included in the vaccines and which could affect vaccine effectiveness. METHODS: Stool specimens were collected by opportunity sampling of children with gastroenteritis who presented to emergency departments. Samples were genotyped for G (VP7) genotypes and P (VP4) genotypes by hemi-nested multiplex PCR methods. Phylogenetic analysis was carried out on Canadian G9 strains to investigate their relationship to G9 strains that have circulated in other regions of the world. RESULTS: 348 samples were collected, of which 259 samples were rotavirus positive and genotyped. There were 34 rotavirus antigen immunoassay negative samples genotyped using PCR-based methods. Over the four rotavirus seasons, 174 samples were G1P[8], 45 were G3P[8], 22 were G2P[4], 13 were G9P[8], 3 were G4P[8] and 2 were G9P[4]. Sequence analysis showed that all Canadian G9 isolates are within lineage III. CONCLUSIONS: Although a limited number of samples were obtained from a median of 4 centres during the 4 years of the study, it appears that currently approved rotavirus vaccines are well matched to the rotavirus genotypes identified at these hospitals. Further surveillance to monitor the emergence of rotavirus genotypes in Canada is warranted.

Urgent air transfers for acute respiratory infections among children from Northern Canada, 2005-2014.

BACKGROUND: The incidence of hospitalizations for acute respiratory infections (ARI) among young Indigenous children from Northern Canada is consistently high. ARIs requiring urgent air transfer can be life-threatening and costly. We aimed to describe their epidemiology, estimate age-specific incidences, and explore factors associated with level of care required. METHODS: We undertook a retrospective cohort study of children <5 years old from Northern Canada transferred by urgent air transport for ARI from 2005 through 2014 to 5 pediatric tertiary care centers in Vancouver, Edmonton, Winnipeg, Ottawa and Montreal. Admissions were identified via ARI-related ICD-9/10 coding and forward sortation area. Descriptive statistics and univariable analyses were performed. RESULTS: Among 650 urgent air transfers, the majority were from Nunavut (n = 349, 53.7%) or Nunavik (n = 166, 25.5%), <6 months old (n = 372, 57.2%), and without underlying comorbidity (n = 458; 70.5%). Estimated annual tertiary care ARI admission rates in infants <1 year old from Nunavut (40.7/1000) and Nunavik (44.5/1000) were tenfold higher than in children aged 1 to 4 years. Bronchiolitis (n = 333, 51.2%) and pneumonia (n = 208, 32.0%) were the most common primary discharge diagnoses. Nearly half required critical care (n = 316, 48.6%); mechanical ventilation rates ranged from 7.2% to 55.9% across centres. The most common primary pathogen was respiratory syncytial virus (n = 196, 30.1%). Influenza A or B was identified in 35 cases (5.4%) and vaccine-preventable bacterial infections in 27 (4.1%) cases. INTERPRETATION: Urgent air transfers for ARI from Northern Canada are associated with high acuity. Variations in levels of care were seen across referral centers, age groups and pathogens.

Risk factors for severe COVID-19 in hospitalized children in Canada: A national prospective study from March 2020-May 2021.

Background: Children living with chronic comorbid conditions are at increased risk for severe COVID-19, though there is limited evidence regarding the risks associated with specific conditions and which children may benefit from targeted COVID-19 therapies. The objective of this study was to identify factors associated with severe disease among hospitalized children with COVID-19 in Canada. Methods: We conducted a national prospective study on hospitalized children with microbiologically confirmed SARS-CoV-2 infection via the Canadian Paediatric Surveillance Program (CPSP) from April 2020-May 2021. Cases were reported voluntarily by a network of >2800 paediatricians. Hospitalizations were classified as COVID-19-related, incidental infection, or infection control/social admissions. Severe disease (among COVID-19-related hospitalizations only) was defined as disease requiring intensive care, ventilatory or hemodynamic support, select organ system complications, or death. Risk factors for severe disease were identified using multivariable Poisson regression, adjusting for age, sex, concomitant infections, and timing of hospitalization. Findings: We identified 544 children hospitalized with SARS-CoV-2 infection, including 60·7% with COVID-19-related disease and 39·3% with incidental infection or infection control/social admissions. Among COVID-19-related hospitalizations (n=330), the median age was 1·9 years (IQR 0·1-13·3) and 43·0% had chronic comorbid conditions. Severe disease occurred in 29·7% of COVID-19-related hospitalizations (n=98/330 including 60 admitted to intensive care), most frequently among children aged 2-4 years (48·7%) and 12-17 years (41·3%). Comorbid conditions associated with severe disease included pre-existing technology dependence requirements (adjusted risk ratio [aRR] 2·01, 95% confidence interval [CI] 1·37-2·95), body mass index Z-scores ≥3 (aRR 1·90, 95% CI 1·10-3·28), neurologic conditions (e.g. epilepsy and select chromosomal/genetic conditions) (aRR 1·84, 95% CI 1·32-2·57), and pulmonary conditions (e.g. bronchopulmonary dysplasia and uncontrolled asthma) (aRR 1·63, 95% CI 1·12-2·39). Interpretation: While severe outcomes were detected at all ages and among patients with and without comorbidities, neurologic and pulmonary conditions as well as technology dependence were associated with increased risk of severe COVID-19. These findings may help guide vaccination programs and prioritize targeted COVID-19 therapies for children. Funding: Financial support for the CPSP was received from the Public Health Agency of Canada.

Pandemic 2009 (A)H1N1 influenza (swine flu) - the Manitoba experience.

The pattern of illness associated with the first wave of the pandemic influenza A H1N1 (swine flu) in the spring and early summer of 2009 in regions of the province of Manitoba in Canada was more severe, on a population basis, than any other northern hemisphere jurisdiction outside of Mexico City. Manitoba accounted for 50% of intensive care admissions and 25% of pediatric admissions, but only 6.5% of deaths, attributable to the virus in Canada during the first wave. Activation and use of emergency response protocols embedded within the routine health authority management system and good communication between the diagnostic laboratory, public health, and health care practitioners was effective in coping with the sudden need for hospitalization of large numbers of children and young adults with severe respiratory illness over a short time period. Early treatment with oseltamivir was associated with a shorter duration of hospitalization among children. Intensive education of health care providers, patients, and visitors, along with close monitoring of infection prevention and control practices, were instrumental in preventing both nosocomial and health care worker infections.

Antimicrobial use among adult inpatients at hospital sites within the Canadian Nosocomial Infection Surveillance Program: 2009 to 2016.

BACKGROUND: Antimicrobial resistance is a growing threat to the world's ability to prevent and treat infections. Links between quantitative antibiotic use and the emergence of bacterial resistance are well documented. This study presents benchmark antimicrobial use (AMU) rates for inpatient adult populations in acute-care hospitals across Canada. METHODS: In this retrospective surveillance study, acute-care adult hospitals participating in the Canadian Nosocomial Infection Surveillance Program (CNISP) submitted annual AMU data on all systemic antimicrobials from 2009 to 2016. Information specific to intensive care units (ICUs) and non-ICU wards were available for 2014-2016. Data were analyzed using defined daily doses (DDD) per 1000 patient days (DDD/1000pd). RESULTS: Between 2009 and 2016, 16-18 CNISP adult hospitals participated each year and provided their AMU data (22 hospitals participated in ≥1 year of surveillance; 11 in all years). From 2009 to 2016, there was a significant reduction in use (12%) (from 654 to 573 DDD/1000pd, p = 0.03). Fluoroquinolones accounted for the majority of this decrease (47% reduction in combined oral and intravenous use, from 129 to 68 DDD/1000pd, p < 0.002). The top five antimicrobials used in 2016 were cefazolin (78 DDD/1000pd), piperacillin-tazobactam (53 DDD/1000pd), ceftriaxone (49 DDD/1000pd), vancomycin (combined oral and intravenous use was 44 DDD/1000pd; 7% of vancomycin use was oral), and ciprofloxacin (combined oral and intravenous use: 42 DDD/1000pd). Among the top 10 antimicrobials used in 2016, ciprofloxacin and metronidazole use decreased significantly between 2009 and 2016 by 46% (p = 0.002) and 26% (p = 0.002) respectively. Ceftriaxone (85% increase, p = 0.0008) and oral amoxicillin-clavulanate (140% increase, p < 0.0001) use increased significantly but contributed only a small component (8.6 and 5.0%, respectively) of overall use. CONCLUSIONS: This study represents the largest collection of dispensed antimicrobial use data among inpatients in Canada to date. Between 2009 and 2016, there was a significant 12% decrease in AMU, driven primarily by a 47% decrease in fluoroquinolone use. Modest absolute increases in parenteral ceftriaxone and oral amoxicillin-clavulanate use were noted but contributed a small amount of total AMU. Ongoing national surveillance is crucial for establishing benchmarks and antimicrobial stewardship guidelines.

Human immunodeficiency virus (HIV) type 1 proviral hypermutation correlates with CD4 count in HIV-infected women from Kenya.

APOBEC3G is an important innate immune molecule that causes human immunodeficiency virus type 1 (HIV-1) hypermutation, which can result in detrimental viral genome mutations. The Vif protein of wild-type HIV-1 counteracts APOBEC3G activity by targeting it for degradation and inhibiting its incorporation into viral particles. Additional APOBEC cytidine deaminases have been identified, such as APOBEC3F, which has a similar mode of action but different sequence specificity. A relationship between APOBEC3F/G and HIV disease progression has been proposed. During HIV-1 sequence analysis of the vpu/env region of 240 HIV-infected subjects from Nairobi, Kenya, 13 drastically hypermutated proviral sequences were identified. Sequences derived from plasma virus, however, lacked hypermutation, as did proviral vif. When correlates of disease progression were examined, subjects with hypermutated provirus were found to have significantly higher CD4 counts than the other subjects. Furthermore, hypermutation as estimated by elevated adenine content positively correlated with CD4 count for all 240 study subjects. The sequence context of the observed hypermutation was statistically associated with APOBEC3F/G activity. In contrast to previous studies, this study demonstrates that higher CD4 counts correlate with increased hypermutation in the absence of obvious mutations in the APOBEC inhibiting Vif protein. This strongly suggests that host factors, such as APOBEC3F/G, are playing a protective role in these patients, modulating viral hypermutation and host disease progression. These findings support the potential of targeting APOBEC3F/G for therapeutic purposes.