BACKGROUND:The COVID-19 pandemic affected the epidemiology of respiratory syncytial virus (RSV). We sought to describe tertiary care hospital admissions associated with pediatric RSV in 2022/23 in Canada and to assess pandemic-related changes. METHODS:We conducted active surveillance of hospital-admitted infants and children aged 0 to 16 years at 13 Immunization Monitoring Program, Active (IMPACT) centres. We compared RSV-associated hospital admissions in 2022/23 with those in the prepandemic period (2017/18 through 2019/20). We calculated province-specific and age-stratified proportions of all-cause hospital admissions with RSV detection and age-stratified proportions of RSV-associated intensive care unit (ICU) admissions. We performed seasonal autoregressive integrated moving average (SARIMA) time-series analyses. RESULTS:In 2022/23, 5362 RSV-associated hospital admissions occurred, including 1260 (23.5%) ICU admissions, both more than double the prepandemic yearly averages. Overall, the median age increased from 6 (interquartile range [IQR] 1 to 20) months to 9 (IQR 2 to 27) months (p < 0.001). The proportion of RSV-associated hospital admissions among all-cause admissions increased by 3.5 percentage points (95% confidence interval [CI] 3.3 to 3.7 percentage points), to 6.8% (95% CI 6.6% to 7.0%). Whereas 41.5% of RSV-associated hospital admissions were among infants younger than 6 months, this age group accounted for 62.1% of ICU admissions. Overall, the ICU proportion remained constant; however, the odds of ICU admission among infants younger than 6 months increased (adjusted odds ratio 1.35, 95% CI 1.2 to 1.52) compared with the prepandemic period. National weekly incidence in 2022/23 peaked earlier and higher, and persisted longer than expected by SARIMA. INTERPRETATION:In 2022/23, the number of RSV-associated hospital admissions and ICU admissions increased dramatically in Canadian pediatric hospitals. The greatest burden remained in infants younger than 6 months. Strategies for RSV immunization for young infants may have a substantial public health impact.

Background:Respiratory syncytial virus (RSV) is a major cause of bronchiolitis and pneumonia in pediatric populations, especially in infancy. This study aims to assess overall and age-specific incidence of RSV-associated hospitalization and healthcare resource use throughout childhood in Canada. Methods:Data were retrieved from a national administrative dataset, which captured hospitalizations with International Classification of Diseases (ICD) codes, tenth revision from participating Canadian hospitals (Canadian Institute for Health Information, CIHI), and from an active surveillance program in tertiary care pediatric hospitals (the Canadian Immunization Program ACTive, IMPACT). Children aged 0-16 years with RSV in November 2017 through April 2023 were eligible. We estimated overall and age-specific RSV hospitalization incidence, healthcare resource use (length of stay, mechanical ventilation use), and costs by age group (0-5, 6-11, and 12-23 months, and 2-4 years, 5-9 years, 10-16 years). Costs were adjusted to 2022 Canadian dollars (CAD). The population denominator for age-specific RSV incidence estimates was retrieved from Statistics Canada. Findings:An estimated 29,277 RSV hospitalizations occurred, with an average of 5831 cases/year in pre-pandemic years (November 2017-June 2020). Infants aged <6 months old accounted for 13,055 (44.6%) of cases for study duration (November 2017-April 2023). RSV incidence among infants aged <6 months increased from 1250 per 100,000 in November 2017-June 2018 to 2393 per 100,000 in July 2022-April 2023. The average annual cost of RSV was $66,267,950 CAD. Infants <6 months old accounted for 49.0% ($32,471,296 CAD) of annual average RSV healthcare costs. Interpretation:Although RSV occurs throughout childhood, the high RSV hospitalization incidence in infants younger than 6 months of age highlights an urgent need for prevention strategies in this population to alleviate the health burden in this population and economic burden on healthcare systems. Funding:This surveillance activity is conducted as part of the Canadian Immunization Monitoring Program Active (IMPACT), a national surveillance initiative managed by the Canadian Paediatric Society (CPS) and conducted by the IMPACT network of pediatric investigators. Funding for RSV surveillance was provided by the Public Health Agency of Canada; funding for RSV economic burden analyses was provided by Sanofi and AstraZeneca.

Background: The Canadian Nosocomial Infection Surveillance Program (CNISP) observed increased mortality among neonatal intensive care unit (NICU) patients with central-line–associated bloodstream infection (CLABSI) starting in 2017. In this study, we compared NICU patients with CLABSIs before and after 2017, and quantified the impact of epidemiological factors on 30-day survival. Methods: We included 1,276 NICU patients from 8–16 participating CNISP hospitals from the pre-2017 period (2009–2016) and the post-2017 period (2017–2022) using standardized definitions and questionnaires. We used Cox regression modeling to assess the impact of age at date of positive culture, sex, birthweight, CLABSI microorganism, region of the country, and surveillance period (before 2017 vs after 2017) on time to 30-day all-cause mortality from date of positive culture. Gestational age was not available for this analysis. We reported model outputs as hazard ratios with 95% CIs. Results: In total, 769 (60%) NICU CLABSIs were reported in the pre-2017 period and 507 (40%) in the post-2017 period. The 30-day all-cause mortality rate was 8% (n = 100 of 1,276) overall, and significantly higher after 2017 (12%, n = 61 of 507) than before 2017 (5%, n = 39 of 769) ( P < .001). During the post-2017 period, cases were significantly younger: 16 days (IQR, 9–33) versus 21 days (IQR, 11–49) ( P = .002). Median days from ICU admission to infection were shorter: 14 (IQR, 8–31) versus 19 (IQR, 10–41) ( P < .001). More gram-negative CLABSIs were identified (29% vs 24%; P = .040) and fewer gram-positive CLABSIs were identified (64% vs 72%; P = .006) compared to the pre-2017 period. Mortality was higher in CLABSIs caused by gram-negative bacteria (15%, n = 50 of 328) than gram-positive bacteria (4.4%, n = 39 of 877) ( P < .001), and mortality was higher in neonates with birthweight <1,000 g (11%, n = 71 of 673) compared to those weighing ≥1,000 g (5%, n = 28 of 560) ( P < .001). Adjusting for all other factors, survival modeling indicated that NICU CLABSIs identified in the post-2017 period had 2.12 (95% CI, 1.23–3.66) times the hazard ratio of 30-day all-cause mortality compared to those before 2017 ( P < .006). Those identified with a gram-positive bacterium had a 0.28 hazard ratio (95% CI, 0.12–0.65) of 30-day mortality compared to those with a gram-negative bacterium or fungus ( P = .003). In the fully adjusted model, age, sex, and birthweight were not significantly associated with NICU CLABSI survival. Conclusions: NICU patients with CLABSIs had significantly higher all-cause mortality between 2017–2022 compared to 2009–2016, and those who acquired gram-positive–associated CLABSIs had improved survival compared to other organisms. Further work is needed to identify and understand factors driving the increased mortality among NICU CLABSI patients from 2017–2022. Disclosures: None

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

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.

Background:Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infection in young children worldwide. Underlying health conditions, especially premature birth, chronic lung disease and congenital heart disease, predispose to severe RSV illness. The only means of prophylaxis against RSV disease is passive prophylaxis with the monoclonal antibody, palivizumab (PVZ) (SynagisTM). The National Advisory Committee on Immunization (NACI) published a statement for PVZ use in 2003. The purpose of this article is to update previous NACI recommendations for the use of PVZ, taking into consideration recent data on RSV burden of illness, effectiveness of PVZ in infants at risk of more severe RSV disease and economic implications of PVZ use. Methods:The NACI Working Group and external experts performed systematic literature reviews on three topics to support updated NACI guidance: 1) RSV burden of disease; 2) PVZ effectiveness; and 3) cost effectiveness of PVZ prophylaxis. Full details and results are presented in the statement and supporting documents. Results:Respiratory syncytial virus hospitalization (RSVH) rates are highest in children younger than one year of age and especially in the first two months of life. In various populations of infants at risk of severe RSV infection, PVZ prophylaxis is associated with reductions of 38%-86% in the risk of RSVH. Only rare cases of anaphylaxis have been reported after decades of use. Palivizumab is expensive and only cost-saving in rare scenarios. Conclusion:Updated NACI recommendations on use of PVZ for the prevention of complications of RSV in infants are now available.

Angela Sinilaite 2 , April Killikelly 2 ; au nom du Comité consultatif national de l'immunisation (CCNI)* Résumé Contexte : Le virus respiratoire syncytial (VRS) est la cause la plus fréquente d'infections des voies respiratoires inférieures chez les enfants en bas âge dans le monde.Les problèmes de santé sous-jacents, notamment la naissance prématurée, une maladie pulmonaire chronique et une cardiopathie congénitale, prédisposent à une forme grave de maladie attribuable au VRS.Le seul moyen de prophylaxie contre les infections à VRS est une protection par immunisation passive avec le palivizumab (PVZ) (Synagis MD ), un anticorps monoclonal.Le Comité consultatif national de l'immunisation (CCNI) a publié une déclaration sur l'utilisation du PVZ en 2003.Le présent article a pour objet de mettre à jour les recommandations précédentes du CCNI concernant l'utilisation du PVZ, en tenant compte des données récentes sur le fardeau de la maladie à VRS, sur l'efficacité réelle du PVZ chez les nourrissons à risque d'une forme plus grave de la maladie à VRS et sur les répercussions économiques associées à l'utilisation du PVZ.Méthodes : Le Groupe de travail du CCNI et les experts externes ont procédé à des examens systématiques de la documentation sur trois sujets afin d'appuyer l'actualisation des documents d'orientation du CCNI : 1) Le fardeau de la maladie lié au VRS, 2) l'efficacité réelle du PVZ et 3) le rapport coût/efficacité de la prophylaxie par PVZ.Les informations et les résultats sont présentés dans leur intégralité dans la déclaration et les documents à l'appui.Résultats : Les taux d'hospitalisation attribuables au virus respiratoire syncytial (HVRS) sont plus élevés chez les enfants de moins d'un an et surtout au cours des deux premiers mois de vie.Dans des populations mixtes de nourrissons à risque d'infection grave par le VRS, la prophylaxie par PVZ est associée à des réductions de 38 à 86 % du risque d'HVRS.Seuls de rares cas d'anaphylaxie ont été signalés après des décennies d'utilisation.Le palivizumab coûte cher et ne permet des économies que dans de rares scénarios. Conclusion :Les recommandations actualisées du CCNI sur l'utilisation du PVZ pour la prévention des complications attribuables au VRS chez les nourrissons sont maintenant disponibles.Citation proposée : Moore D, Sinilaite A, Killikelly A, au nom du Comité consultatif national de l'immunisation (CCNI).« Sommaire de la mise à jour de la déclaration du Comité consultatif national de l'immunisation (CCNI) sur l'utilisation recommandée du palivizumab pour réduire les complications de l'infection par le virus respiratoire syncytial chez les nourrissons ».

Respiratory syncytial virus (RSV) infections are common among young children and represent a significant burden to patients, their families and the Canadian health system. Here we conduct a rapid review of the burden of RSV illness in children 24 months of age or younger. Four databases (Medline, Embase, Cochrane Database of Clinical Trials, ClinicalTrials.gov from 2014 to 2018), grey literature and reference lists were reviewed for studies on the following: children with or without a risk factor, without prophylaxis and with lab-confirmed RSV infection. Of 29 studies identified, 10 provided within-study comparisons and few examined clinical conditions besides prematurity. For infants of 33-36 weeks gestation (wGA) versus term infants, there was low-to-moderate certainty evidence for an increase in RSV-hospitalizations (n=599,535 infants; RR 2.05 [95% CI 1.89-2.22]; 1.3 more per 100 [1.1-1.5 more]) and hospital length of stay (n=7,597 infants; mean difference 1.00 day [95% CI 0.88-1.12]). There was low-to-moderate certainty evidence of little-to-no difference for infants born at 29-32 versus 33-36 wGA for hospitalization (n=12,812 infants; RR 1.20 [95% CI 0.92-1.56]). There was low certainty evidence of increased mechanical ventilation for hospitalized infants born at 29-32 versus 33-35 wGA (n=212 infants; RR 1.58, 95% CI 0.94-2.65). Among infants born at 32-35 wGA, hospitalization for RSV in infancy may be associated with increased wheeze and asthma-medication use across six-year follow-up (RR range 1.3-1.7). Children with versus without Down syndrome may have increased hospital length of stay (n=7,206 children; mean difference 3.00 days, 95% CI 1.95-4.05; low certainty). Evidence for other within-study comparisons was of very low certainty. In summary, prematurity is associated with greater risk for RSV-hospitalization and longer hospital length of stay, and Down syndrome may be associated with longer hospital stay for RSV. Respiratory syncytial virus-hospitalization in infancy may be associated with greater wheeze and asthma-medication use in early childhood. Lack of a comparison group was a major limitation for many studies.

Les infections par le virus respiratoire syncytial sont fréquentes chez les jeunes enfants et représentent un fardeau important pour les patients, leurs familles et le système de santé canadien. Nous procédons ici à un examen rapide du fardeau lié au virus respiratoire syncytial chez les enfants âgés de 24 mois ou moins. Quatre bases de données (Medline, Embase, Cochrane Database of Clinical Trials, ClinicalTrials.gov de 2014 à 2018), la littérature grise et les listes de référence ont été examinées pour trouver des études portant sur les éléments suivants : enfants avec ou sans facteur de risque, sans prophylaxie et avec une infection par le virus respiratoire syncytial confirmée en laboratoire. Sur les 29 études trouvées, 10 ont fourni des comparaisons intraétudes et peu ont fait l’examen des conditions cliniques autres que la prématurité. Pour les nourrissons âgés de 33 à 36 semaines de grossesse (SG) par rapport aux nourrissons nés à terme, il existe des preuves de certitude faible à modérée d’une augmentation des hospitalisations dues au virus respiratoire syncytial (n = 599 535 nourrissons; RR 2,05 [IC 95 % 1,89 à 2,22]; 1,3 de plus pour 100 [1,1 à 1,5 de plus]) et de la durée d’hospitalisation (n = 7 597 nourrissons; différence moyenne de 1,00 jour [IC 95 % 0,88 à 1,12]). Il y avait des preuves de certitude faible à modérée d’une différence faible à nulle entre les nourrissons nés entre 29 à 32 SG et ceux nés entre 33 à 36 SG pour l’hospitalisation (n = 12 812 nourrissons; RR 1,20 [IC 95 % 0,92 à 1,56]). Il existe des preuves de faible certitude d’une ventilation mécanique accrue pour les nourrissons hospitalisés nés à 29 à 32 SG par rapport à 33 à 35 SG (n = 212 nourrissons; RR 1,58; IC 95 % 0,94 à 2,65). Chez les nourrissons nés entre 32 et 35 SG, l’hospitalisation pour le virus respiratoire syncytial dans la petite enfance peut être associée à une augmentation de la respiration sifflante et de l’utilisation de médicaments contre l’asthme au cours du suivi de six ans (RR de 1,3 à 1,7). Les enfants atteints du syndrome de Down peuvent avoir une durée d’hospitalisation plus longue que ceux qui n’en sont pas atteints (n = 7 206 enfants; différence moyenne de 3,00 jours, IC 95 % 1,95 à 4,05; certitude faible). Les preuves pour les autres comparaisons intraétudes étaient d’un niveau de certitude très faible. En résumé, la prématurité est associée à un risque plus élevé d’hospitalisation pour le virus respiratoire syncytial et à une durée d’hospitalisation plus longue, et le syndrome de Down peut être associé à une hospitalisation plus longue pour le virus respiratoire syncytial. L’hospitalisation due au virus respiratoire syncytial dans la petite enfance peut être associée à une plus grande respiration sifflante et à une plus grande utilisation de médicaments contre l’asthme dans la petite enfance. L’absence de groupe de comparaison a constitué une limite majeure pour de nombreuses études.

Respiratory syncytial virus (RSV) can cause severe disease in infants and older adults.Various vaccine candidates are in development and may become authorized for use in Canada within the next 2-5 years.The Public Health Agency of Canada sought to enhance preparedness for RSV vaccine and passive immunization candidates by organizing an expert retreat to identify knowledge gaps in surveillance and research and development in the context of provincial and territorial RSV public health priorities.We determined that RSV candidate vaccines in development directly address four out of five identified public health priorities, and identified remaining data gaps around vaccine efficacy and effectiveness.We determined that limited or sufficient surveillance data is available to support decision-making for four out of five RSV public health priorities and identified data gaps for several key populations: (i) for RSV cases under 17 years of age, gaps remain for denominator data to calculate incidence and data on medically attended outpatient visits; (ii) for RSV cases in Indigenous and remote communities, gaps remain for data on incidence, prevalence, specific risk factors, feasibility and acceptability; and (iii) for RSV cases in older adults, gaps remain for data on incidence.This process demonstrated the feasibility of, and stakeholder support for, gap analyses in surveillance data to support decisions about prospective vaccines and immune products.

Background: Neurological 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. Methods: This 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. Results: Sixty-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-mumpsrubella, 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. Conclusions: Encephalopathy/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. (C) 2020 The Authors. Published by Elsevier Ltd.

Un vaccin contre le virus respiratoire syncytial (VRS) est activement recherché depuis plus de 60 ans en raison des effets de la maladie du VRS sur la santé des nourrisons.Toutefois, la seule mesure préventive disponible actuellement au Canada et ailleurs se limite à l'immunisation passive des nourrissons et enfants à haut risque avec un anticorps monoclonal.Plusieurs obstacles empêchent la création d'un vaccin contre le VRS, notamment l'aggravation de la maladie chez les nourrissons causée par le vaccin.Au cours des dix dernières années, plusieurs avancées importantes dans les domaines de l'immunologie cellulaire et de la structure des protéines ont conduit au passage de nouveaux produits en phase finale de développement clinique.En date de juillet 2019, 16 organismes mènent 121 essais cliniques sur la mise au point d'un vaccin contre le VRS.Cinq technologies dominent le domaine de la création d'un vaccin contre le VRS : quatre agents d'immunisation active (vaccins vivants atténués, à base de particules, à sous-unités et à base de vecteurs) et un nouvel agent d'immunisation passive (anticorps monoclonal).Des essais cliniques de phase 3 des candidats vaccins pour les femmes enceintes, les nourrissons, les enfants et les personnes âgées sont en cours.La prévention du VRS changera énormément dans les dix prochaines années.

BACKGROUND:Annual influenza vaccination is recommended for all individuals six months of age and older, including those with HIV infection. Prior to this statement, the National Advisory Committee on Immunization (NACI) stated that live attenuated influenza vaccine (LAIV) was contraindicated for all individuals with HIV infection. The objective of this article is to update NACI's guidance on the use of LAIV for HIV-infected individuals.METHODS:A systematic literature review of the use of LAIV in individuals with HIV was undertaken. The Canadian Adverse Events Following Immunization Surveillance System was searched for reports of adverse events following vaccination with LAIV in HIV-infected individuals. NACI approved the revised recommendations.RESULTS:NACI concluded that LAIV is immunogenic in children with HIV, and available data suggest that it is safe, although data were insufficient to detect possible uncommon adverse effects. LAIV may be considered as an option for vaccination of children 2-17 years old who meet the following criteria: 1) receiving highly active antiretroviral therapy for at least four months; 2) CD4 count of 500/µL or greater if age 2-5 years, or of 200/µL or greater if age 6-17 years; and 3) HIV plasma RNA less than 10,000 copies/mL. LAIV remains contraindicated for adults with HIV because of insufficient data. Intramuscular influenza vaccination is considered the standard for children living with HIV by NACI and the Canadian Paediatric & Perinatal HIV/AIDS Research Group, particularly for those without HIV viral load suppression (i.e. plasma HIV RNA is 40 copies/mL or greater). However, if intramuscular (IM) vaccination is not accepted by the patient or substitute decision-maker, LAIV would be reasonable for children meeting the criteria listed above.CONCLUSION:LAIV may be considered as an option for annual vaccination of selected children with HIV.

Robyn Harrison 5,6 au nom du Comité consultatif national de l'immunisation (CCNI)* Résumé Contexte : La vaccination annuelle contre la grippe est recommandée pour toutes les personnes âgées de six mois et plus, y compris celles qui sont infectées par le VIH.Avant cette déclaration, le Comité consultatif national de l'immunisation (CCNI) a déclaré que le vaccin vivant atténué contre l'influenza (VVAI) était contre-indiqué pour toutes les personnes infectées par le VIH.L'objectif du présent article est de mettre à jour les directives du CCNI sur l'utilisation du VVAI pour les personnes infectées par le VIH.Méthodes : On a entrepris un examen systématique de la littérature sur l'utilisation du VVAI chez les personnes atteintes du VIH.Le Système canadien de surveillance des effets secondaires suivant l'immunisation a fait l'objet d'une recherche pour trouver des signalements d'effets secondaires à la suite de la vaccination avec un VVAI chez les personnes infectées par le VIH.Le CCNI approuve les recommandations révisées.Résultats : Le CCNI a conclu que le VVAI est immunogène chez les enfants atteints du VIH et les données disponibles suggèrent qu'il est sans danger, même si elles étaient insuffisantes pour détecter d'éventuels effets secondaires inhabituels.Le VVAI peut être considéré comme une option de vaccination des enfants âgés de 2 à 17 ans qui respectent les critères suivants : 1) recevoir un traitement antirétroviral hautement actif pendant au moins quatre mois; 2) avoir une numération des CD4 de 500/µL ou plus si l'enfant est âgé est de 2 à 5 ans, ou de 200/µL ou plus si l'enfant est âgé de 6 à 17 ans et 3) l'ARN plasmatique du VIH est inférieur à 10 000 copies/ml.Le VVAI reste contre-indiqué pour les adultes atteints du VIH en raison de données insuffisantes.Le CCNI et le Groupe canadien de recherche pédiatrique et périnatale sur le VIH/sida considèrent la vaccination intramusculaire contre la grippe comme étant la norme pour les enfants affectés par le VIH, en particulier pour ceux qui n'ont pas de suppression de la charge virale pour le VIH (i.e.que l'ARN plasmatique du VIH est de 40 copies/ ml ou plus).Toutefois, si la vaccination intramusculaire n'est pas acceptée par le patient ou le décideur substitut, le VVAI serait raisonnable pour les enfants qui répondent aux critères énumérés ci-dessus. Conclusion :Le VVAI peut être considéré comme une option de vaccination annuelle pour certains enfants atteints du VIH.

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

Le virus respiratoire syncytial (VRS) peut provoquer des maladies graves chez les nourrissons et les personnes âgées.Plusieurs candidats vaccins sont en cours de développement et leur utilisation pourrait être autorisée au Canada dans les deux à cinq prochaines années.L'Agence de la santé publique du Canada s'est employée à améliorer le niveau de préparation à l'introduction du vaccin contre le VRS et de candidats vaccins pour l'immunisation passive en organisant une retraite d'experts, dont l'objectif consistait à cerner les lacunes dans les connaissances en matière de surveillance et de recherche et développement, et ce, sous l'angle des priorités de santé publique des provinces et des territoires concernant le VRS.Nous avons déterminé que les candidats vaccins contre le VRS en cours de développement répondaient pleinement à quatre des cinq priorités de santé publique, et avons mis en

The benefits of human immunodeficiency virus (HIV) testing in pregnancy, when combined with appropriate maternal antiretroviral therapy and intrapartum and postnatal prophylaxis, are well established. The vertical rate of transmission of HIV in North America is now well below 2%. Efforts must continue to ensure that these benefits are sustained. Women who have received little or no prenatal care and those who present for delivery with unknown HIV status need immediate testing. As more infants are exposed to antiretroviral agents, strategies need to be implemented to ensure adequate follow-up of these infants. Issues relating to the identification of HIV-exposed infants are highlighted.

Lorsqu’il est combiné à un traitement antirétroviral prénatal approprié et à une prophylaxie intrapartum et postnatale, le dépistage du virus de l'immunodéficience humaine (VIH) pendant la grossesse comporte des avantages bien établis. Le taux de transmission verticale du VIH en Amérique du Nord se situe maintenant bien en deçà de 2 %. Les efforts doivent se poursuivre pour maintenir ces avantages. Les femmes qui ont reçu peu de soins prénatals, sinon aucuns, et celles qui accouchent sans qu’on connaisse leur état sérologique doivent faire l’objet d’un dépistage immédiat. Puisque plus de nouveau-nés sont exposés à des agents antirétroviraux qu’auparavant, des stratégies sont à prévoir pour leur assurer un suivi convenable. Les enjeux relatifs au dépistage des nouveau-nés exposés au VIH sont présentés.

Background: Systemic inflammation, platelet dysfunction, and endothelial activation persist in people living with HIV despite sustained virologic suppression (SVS) with combined antiretroviral therapy (cART) and may lead to complications such as atherosclerosis and cardiovascular disease. Angiopoietin-1 (Ang-1) is a key regulator of angiogenesis and endothelial activation and has been studied as an objective biomarker in disease states such as atherosclerosis, sepsis, and severe malaria. Setting: Eight pediatric HIV care centers across Canada. Methods: Cross-sectional study of 61 children living with vertically acquired HIV on cART with undetectable RNA viral load. Plasma levels of Ang-1 were measured by ELISA and analyzed in relation to clinical characteristics abstracted from medical records. Results: Ang-1 levels were directly correlated with clinical indices of virologic control: cumulative proportion of life on effective cART (r = +0.35, P = 0.0078) and cumulative proportion of life with SVS (r = +0.36, P = 0.0049). Furthermore, higher Ang-1 levels were associated with younger age at SVS (r = 20.56, P, 0.0001). These associations remained statistically significant in multivariable linear regression models adjusting for potential confounders (P < 0.05 for all associations). Conclusions: Early effective cART and SVS were associated with higher Ang-1 levels in children living with vertically acquired HIV-1.

Objective Dolutegravir is recommended worldwide as a first-line antiretroviral therapy (ART) for individuals living with HIV. A recent study reported increased rates of neural tube defects in infants of dolutegravir-treated women. This study examined rates of congenital anomalies in infants born to women living with HIV (WLWH) in Canada. Design The Canadian Perinatal HIV Surveillance Programme captures surveillance data on pregnant WLWH and their babies and was analysed to examine the incidence of congenital anomalies. Setting Paediatric HIV clinics. Population Live-born infants born in Canada to WLWH between 2007 and 2017. Methods Data on mother-infant pairs, including maternal ART use at conception and during pregnancy, are collected by participating sites. Main outcome measures Congenital anomalies. Results Of the 2423 WLWH, 85 (3.5%, 95% CI 2.85-4.36%) had non-chromosomal congenital anomalies. There was no evidence of a significant difference in rates of congenital anomalies between women who were on ART in their first trimester (3.9%, CI 1.7-7.6%) or later in the pregnancy (3.9%, 95% CI 2.6-5.6%). Four of the 80 (5.0%, 95% CI 1.4-12.3%) neonates born to WLWH on dolutegravir during the first trimester had congenital anomalies, none were neural tube defects (95% CI 0.00-3.10%). Conclusion Despite recent evidence raising a safety concern, this analysis found no signal for increased congenital anomalies. Tweetable abstract Five percent of the infants of Canadian women living with HIV on dolutegravir at conception had congenital anomalies; none had neural tube defects.