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Respiratory syncytial virus (RSV) is the leading viral cause of childhood bronchiolitis and pneumonia causing over 3 million hospitalizations and 100,000 deaths in children under 5 years of age annually. Wastewater-based surveillance (WBS) has proven an effective early warning system for high-consequence pathogens, including SARS-CoV-2, polio, mpox, and influenza, but has yet to be fully leveraged for RSV surveillance. A model predicated on the Canadian province of Ontario demonstrates that implementation of a WBS system can potentially result in significant cost savings and clinical benefits when guiding an RSV preventive program with a long-acting monoclonal antibody. A network of integrated WBS initiatives offers the opportunity to help minimize the devastating global burden of RSV in children by optimizing the timing of preventive measures and we strongly advocate that its benefits continue to be explored., Competing Interests: RD and EM have no conflicts to declare regarding this study but hold leadership positions in a company (Advanced Environmental Molecular Analytics Ltd.) with work non-relevant to the work presented. BP has received research funding and/or compensation as advisor/lecturer from AstraZeneca and Sanofi outside the scope of this study. BR-G and JE were employed by the company Violicom Medical Limited. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Thampi, Mercier, Paes, Edwards, Rodgers-Gray and Delatolla.)

Introduction: Detection of community respiratory syncytial virus (RSV) infections informs the timing of immunoprophylaxis programs and hospital preparedness for surging pediatric volumes. In many jurisdictions, this relies upon RSV clinical test positivity and hospitalization (RSVH) trends, which are lagging indicators. Wastewater-based surveillance (WBS) may be a novel strategy to accurately identify the start of the RSV season and guide immunoprophylaxis administration and hospital preparedness., Methods: We compared citywide wastewater samples and pediatric RSVH in Ottawa and Hamilton between August 1, 2022, and March 5, 2023. 24-h composite wastewater samples were collected daily and 5 days a week at the wastewater treatment facilities in Ottawa and Hamilton, Ontario, Canada, respectively. RSV WBS samples were analyzed in real-time for RSV by RT-qPCR., Results: RSV WBS measurements in both Ottawa and Hamilton showed a lead time of 12 days when comparing the WBS data set to pediatric RSVH data set (Spearman's ρ = 0.90). WBS identify early RSV community transmission and declared the start of the RSV season 36 and 12 days in advance of the provincial RSV season start (October 31) for the city of Ottawa and Hamilton, respectively. The differing RSV start dates in the two cities is likely associated with geographical and regional variation in the incidence of RSV between the cities., Discussion: Quantifying RSV in municipal wastewater forecasted a 12-day lead time of the pediatric RSVH surge and an earlier season start date compared to the provincial start date. These findings suggest an important role for RSV WBS to inform regional health system preparedness, reduce RSV burden, and understand variations in community-related illness as novel RSV vaccines and monoclonal antibodies become available., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Mercier, Pisharody, Guy, Wan, Hegazy, D’Aoust, Kabir, Nguyen, Eid, Harvey, Rodenburg, Rutherford, Mackenzie, Willmore, Hui, Paes, Delatolla and Thampi.)

Background: The main objective was to determine the incidence, management, and outcomes of respiratory syncytial virus nosocomial infection (RSVNI) outbreaks in neonatal intensive care units., Methods: A comprehensive search of RSVNI in 9 databases was conducted from January 1, 2000 to May 1, 2021, of which the Cochrane Library comprised the Cochrane central register of controlled trials and the Cochrane database of systematic reviews. Two hundred and twenty-eight articles were retrieved and 17 were retained. A descriptive analysis was performed, and frequencies are reported as mean, median, and range where pertinent., Results: One hundred and seventeen infants were analyzed and comprised preterms (88.1%) and those with pre-existing co-morbidities. The estimated proportional incidence of RSVNI was 23.8% (177/744) infants. Outbreaks were principally managed by conventional protective measures, neonatal intensive care unit closure, and visitor restriction. Palivizumab was used to control RSVNI in 10 studies. RSVNI-related mortality was 8.5% (15/177) and 8.0% (7/87) among infants where infection control was solely employed., Conclusion: RSVNI is associated with significant morbidity and mortality. The use of palivizumab should be a multidisciplinary decision, based on rapidly spreading infection. Prospective studies are essential to determine the cost-benefit of palivizumab versus standard prevention control for an RSVNI outbreak., (Copyright © 2021 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: The aim of this study is to compare respiratory illness-related hospitalization (RIH) and respiratory syncytial virus (RSV)-related hospitalization (RSVH) in multiple births versus singletons, who received palivizumab during the RSV season and participated in the Canadian registry of palivizumab (CARESS)., Study Design: Prospective, observational study of infants aged <2 years recruited across 32 centers over 12 RSV seasons from 2005 to 2017. Demographic data were collected at enrolment and RIH events were recorded monthly., Results: A total of 25,003 infants were enrolled of whom 6,949 (27.8%) were of multiple birth, and 18,054 (72.2%) were singletons. A significantly larger proportion of the multiple births were premature (80.2%) compared with the singleton group (56.8%). Multiples had a lower gestational age (mean ± standard deviation): 31.2 ± 3.2 versus 33.2 ± 5.5 weeks and birth weight (mean: 1,590 ± 606.8 vs. 2,069.4 ± 1068.5 g; both p  < 0.0005). They were younger at enrolment (4.5 ± 5.0 vs. 6.1 ± 6.8 months), and fewer attended daycare (1.9 vs. 4.6%), and experienced exposure to smoking (24.5 vs. 29.9%), but more lived in a crowded household (36.7 vs. 19.4%); all p  < 0.0005. Multiples had a longer length of neonatal stay (51.1 ± 65.9 vs. 47.9 ± 67.8 days), and more required respiratory support (65.7 vs. 57.7%), but for shorter duration (22.6 ± 32.9 vs. 24.7 ± 40.6 days); all p  < 0.001. RIH and RSVH rates (%) in multiples versus singletons were 4.7; 7.7 and 1.4; and 1.6, respectively. Cox regression showed that multiples had a lower risk of RIH compared with singletons (hazard ratio [HR] = 0.616, 95% confidence interval [CI]: 0.543-0.698, p  < 0.0005), but not RSVH (HR: 0.77, 95% CI: 0.57-1.02, p  = 0.071)., Conclusion: Multiple birth infants, who are known to be at greater risk for severe RSVH compared with singletons, are well protected by palivizumab, provided adherence to the monthly injection scheme is guaranteed., Competing Interests: B.P., I.M., and K.L.L. have received investigator initiated research funding or received compensation as advisors or lecturers from AbbVie Corporation, Merck and MedImmune. A.L. and D.K. have no conflict of interest to declare. B.P. wrote the first draft of the manuscript. No honorarium, grant, or other form of payment was given to anyone to produce the manuscript., (Thieme. All rights reserved.)

Objective: The advisory board to the Ontario Ministry of Health considered adopting the new three-variable international risk scoring tool (IRST) to guide prophylaxis against respiratory syncytial virus hospitalization (RSVH) in moderate-to-late preterm infants born 32-35 weeks' gestational age (wGA). Canada currently uses a nationally validated, seven-variable RST, to predict RSVH in 33-35 wGA infants. We explored the potential implications of switching from the Canadian to the IRST., Methods: Predictive accuracy (area under the receiver operating characteristic curve [AUROC]) of the two RSTs and correlations (Spearman rank) and number needed to treat (NNT) between cut-off scores for low-, moderate- and high-risk subjects were assessed., Results: The RSTs contain many of the same risk factors (birth proximity to the RSV season, smoking, siblings, daycare), with the Canadian RST also including sex, small for GA and familial eczema. Predictive accuracy was similar (AUROC, IRST: 0.773 [sensitivity: 68.9%; specificity: 73.0%] vs Canadian: 0.762 [68.2%; 71.9%]). Significant correlations between cut-off scores ( p  < .001) and risk categories ( p  < .001) were apparent, although the correlation coefficients were weak for both (scores: 0.217; categories: 0.055). While the proportion of high-risk infants was similar (IRST: 0.7% vs Canadian: 0.6%), the NNT was lower for the Canadian RST (7.5 vs 14.3), and more infants were assigned moderate risk by the IRST (19.9% vs 9.8%)., Conclusions: The IRST can be considered simpler (fewer risk factors) than the Canadian RST and its adoption may reduce the number of RSVHs among moderate-to-late preterm infants; however, the cost-effective implications for RSV prophylaxis warrant further investigation.

Introduction: Respiratory syncytial virus (RSV) causes approximately 120,000 deaths annually in children <5 years, with 99% of fatalities occurring in low- and middle-income countries (LMICs)., Areas Covered: There are numerous RSV interventions in development, including long-acting monoclonal antibodies, vaccines (maternal and child) and treatments which are expected to become available soon. We reviewed the key challenges and issues that need to be addressed to maximize the impact of these interventions in LMICs. The epidemiology of RSV in LMICs was reviewed (PubMed search to 30 June 2020 inclusive) and the need for more and better-quality data, encompassing hospital admissions, community contacts, and longer-term respiratory morbidity, emphasized. The requirement for an agreed clinical definition of RSV lower respiratory tract infection was proposed. The pros and cons of the new RSV interventions are reviewed from the perspective of LMICs., Expert Opinion: We believe that a vaccine (or combination of vaccines, if practicable) is the only viable solution to the burden of RSV in LMICs. A coordinated program, analogous to that with polio, involving governments, non-governmental organizations, the World Health Organization, the manufacturers and the healthcare community is required to realize the full potential of vaccine(s) and end the devastation of RSV in LMICs.

Purpose: Evaluate parental knowledge of respiratory syncytial virus (RSV) and other respiratory infections in preterm infants., Design: Survey., Sample: Five hundred and eighty-three parents of preterm infants with generalized, Canadian provincial representation., Main Outcome: Knowledge of RSV infection, sources of information, and parental understanding of disease risk., Results: 97.9 percent (571/583) of the parents had heard about RSV, since they all had a preterm infant. Sixty-one percent reported having good knowledge of RSV; 19.4 percent had very good knowledge; 19.7 percent had little or no awareness of RSV-related infection. Most (86.3 percent) believed that RSV illness was a very serious condition; 13 percent recognized that it could be a major problem for their child. Principal sources of information were the nurse, doctor and pamphlets. Over 480 participants cited 3 or more sources of additional information-Internet, social media platforms, and educational sessions. Respiratory syncytial virus prophylaxis was a priority, but knowledge regarding the eligibility criteria for prophylaxis is essential., (© Copyright 2021 Springer Publishing Company, LLC.)

To provide comprehensive information on the epidemiology and burden of respiratory syncytial virus hospitalisation (RSVH) in preterm infants, a pooled analysis was undertaken of seven multicentre, prospective, observational studies from across the Northern Hemisphere (2000-2014). Data from all 320-356 weeks' gestational age (wGA) infants without comorbidity were analysed. RSVH occurred in 534/14 504 (3.7%) infants; equating to a rate of 5.65 per 100 patient-seasons, with the rate in individual wGA groups dependent upon exposure time (P = 0.032). Most RSVHs (60.1%) occurred in December-January. Median age at RSVH was 88 days (interquartile range (IQR): 54-159). Respiratory support was required by 82.0% of infants: oxygen in 70.4% (median 4 (IQR: 2-6) days); non-invasive ventilation in 19.3% (median 3 (IQR: 2-5) days); and mechanical ventilation in 10.2% (median 5 (IQR: 3-7) days). Intensive care unit admission was required by 17.9% of infants (median 6 days (IQR: 2-8) days). Median overall hospital length of stay (LOS) was 5 (IQR: 3-8) days. Hospital resource use was similar across wGA groups except for overall LOS, which was shortest in those born 35 wGA (median 3 vs. 4-6 days for 32-34 wGA; P < 0.001). Strategies to reduce the burden of RSVH in otherwise healthy 32-35 wGA infants are indicated.

Respiratory syncytial virus (RSV) infection is a leading cause of hospitalisation in early childhood and palivizumab is the only licensed intervention for prevention. Palivizumab guidelines should reflect the latest evidence, in addition to cost-effectiveness and healthcare budgetary considerations. RSV experts from Europe, Canada and Israel undertook a systematic review of the evidence over the last 5 years and developed recommendations regarding prophylaxis in industrialised countries. Almost 400 publications were reviewed. This group recommended palivizumab for: preterm infants (<29 and ≤31 weeks gestational age [wGA] and ≤9 and ≤6 months of age, respectively; high-risk 32-35wGA), former preterm children ≤24 months with chronic lung disease/bronchopulmonary dysplasia, children ≤24 months with significant congenital heart disease; and other high-risk populations, such as children ≤24 months with Down syndrome, pulmonary/neuromuscular disorders, immunocompromised, and cystic fibrosis. Up to 5 monthly doses should be administered over the RSV season. It is our impression that the adoption of these guidelines would help reduce the burden of RSV., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Infants with congenital diaphragmatic hernia (CDH) are at an increased risk of respiratory morbidity from recurrent respiratory tract infections including those from respiratory syncytial virus (RSV). Prospective studies on RSV prophylaxis in CDH infants are limited. We determined the risk of respiratory illness- and RSV-related hospitalizations (RIH and RSVH, respectively) among infants prophylaxed for CDH, standard indications (SIs) and those without increased risk (NR)., Methods: The prospective Canadian Respiratory Syncytial Virus Evaluation Study of Palivizumab (CARESS) registry was searched for infants who received palivizumab during 12 RSV seasons (2005-2017) in Canada. Cox proportional hazards analyses were conducted to compare RIH and RSVH risks across the groups adjusted for potential confounders., Results: In total, 21 107 infants (201 CDH, 389 NR, and 20 517 SI) were included. RIH incidences were 10.0% (CDH), 2.1% (NR), and 6.2% (SI). CDH patients had a significantly higher RIH hazard compared with NR (hazard ratio [HR], 3.6 [95% confidence interval {CI}, 1.5-8.8]; P = .005) but not SI (HR, 1.2 [95% CI, .8-2.0]; P = .379). RSVH incidences were 0.6%, 0.3%, and 1.5% for CDH, NR, and SI, respectively. RSVH risk was similar across groups (SI: HR, 0.0, P = .922; NR: HR, 0.0, P = .934)., Conclusions: CDH infants had a 3-fold increased risk of RIH compared to NR but not SI infants. RSVH risk was similar with low RSVH incidences across all groups, implying that CDH infants may benefit from palivizumab during the RSV season, similar to other high-risk groups., Clinical Trials Registration: NCT00420966., (© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America.)

Data on respiratory-related illness and respiratory syncytial virus (RSV) infection in children with a tracheostomy are sparse. We determined respiratory illness hospitalization (RIH) and RSV-related hospitalization (RSVH) hazard ratios in children with a tracheostomy following prophylaxis compared with infants' prophylaxed for standard indications (prematurity ≤ 35 weeks' gestational age, bronchopulmonary dysplasia, and significant congenital heart disease) and children with complex medical disorders. Children who received ≥ 1 injection of palivizumab were prospectively enrolled across 32 Canadian sites during the RSV season. Respiratory illness event data were collected monthly. Data were analyzed using t tests, chi-square tests, and Cox proportional hazards adjusted for confounders. A total of 23,597 infants were enrolled; 220 tracheostomy, 19,402 standard indications, 3975 complex medical disorders. Of the 220 tracheostomy infants, 30 had bronchopulmonary dysplasia, 18 were premature, 12 had congenital heart disease, and 160 had other medical complexities. RIH and RSVH incidences (tracheostomy, standard indications, complex medical disorders) were 24.5%, 6.2%, and 9.8% and 2.0%, 1.5%, and 1.8% respectively. RIH hazard was significantly higher in tracheostomy infants compared with standard indications (HR = 1.8, 95% CI 1.1-3.0, p = 0.02) but was similar between the tracheostomy and complex medical disorders groups (HR = 1.3, 95% CI 0.7-2.2, p = 0.37). RSVH hazard was also similar in tracheostomy infants relative to standard indications and complex medical disorders (both p > 0.75). Children with tracheostomies who received palivizumab had an increased RIH hazard compared with the standard indications group. Similar RSVH hazard between tracheostomy, standard indications, and complex medical disorders groups suggests that children with tracheostomies may benefit from palivizumab by reducing RSVH during the RSV season.

Introduction: The use of palivizumab for the prevention of respiratory syncytial virus-related hospitalization is well-established and has been adopted universally in pediatric position statements. Areas covered: The definition of chronic lung disease (CLD, bronchopulmonary dysplasia) has evolved over time and has significantly impacted the reported incidence of the condition, and the description of mild, moderate and severe disease in published studies. We reviewed lung function in infancy, childhood and adulthood of healthy preterm infants and those with CLD and how alterations in airway function, especially following respiratory syncytial virus infection may set the stage for chronic obstructive pulmonary disease in adults. We also characterized the real-world experience of the use of palivizumab compared to the single, randomized trial and examined the socioeconomic burden of respiratory syncytial virus hospitalization, an element that is commonly overlooked, when considering the value of prevention in the extremely high-risk, CLD population. Expert opinion: Based on the current evidence, we propose that palivizumab should be offered to all children with CLD in the first two years of life, irrespective of CLD disease severity. This may positively influence pulmonary maturation and normalize the trajectory of compromised lung function in these children into adulthood.

An observational study was conducted of children < 2 years who received ≥ 1 dose of palivizumab in 32 Canadian institutions from 2005 to 2017. We compared respiratory illness (RIH) and respiratory syncytial virus-related hospitalization (RSVH) hazards in children with a congenital airway anomaly (CAA) versus those prophylaxed for standard indications (SI) and serious medical disorders (SMD). Data were assembled on neonatal course, demographics, palivizumab utilization and adherence, and respiratory illness events, and analyzed using ANOVA, chi-square tests and Cox proportional hazards. Twenty-five thousand three children (1219 CAA, 3538 SMD, and 20,246 SI) were enrolled. Palivizumab adherence was 74.8% overall and similar across groups. For 2054 respiratory-related events, 1724 children were hospitalized. RIH rates were 13.6% (CAA), 9.6% (SMD), and 6.0% (SI). RSVH rates were 2.4% (CAA), 1.6% (SMD), and 1.5% (SI). After adjustment for demographic and neonatal differences, children with a CAA had a significantly increased RIH and RSVH hazard relative to SI (RIH, HR = 1.6, 95% CI 1.2-2.2, p = 0.002; RSVH, HR = 2.1, 95% CI 1.0-4.4, p = 0.037) but similar to SMD (RIH, HR = 1.3, 95% CI 0.9-1.9, p = 0.190; RSVH, HR = 1.7, 95% CI 0.7-4.1, p = 0.277).Conclusion: Children with a CAA experience higher RIH risk. RSVH hazard was similar between CAA and SMD but higher for CAA compared to SI, implying that this population requires surveillance for RSV prophylaxis. What is Known: • Children with congenital airway anomalies (CAA) are at risk for respiratory tract illness and respiratory syncytial virus-related hospitalization (RSVH) with accompanying morbidity and mortality • RSV prophylaxis may be useful in children with a CAA, but is not routinely recommended What is New: • Children with a CAA had a 1.6-2.3 fold greater risk of respiratory-related hospitalization and RSVH compared to those prophylaxed for standard, approved indications and serious medical disorders. • RSVH risk in children aged < 2 years with either upper or lower airway anomalies is similar. Children with a CAA require careful surveillance during the RSV season and prophylaxis may be appropriate.

Children with medical complexity (CMC) are vulnerable to respiratory illness hospitalization (RIH) and respiratory syncytial virus (RSV)-related hospitalization (RSVH) due to multisystem disorders and compromised airways. It is unknown whether RSV prophylaxis is effective, or if RSVH is associated with significant morbidities in CMC. The study objectives were to (1) determine the incidence of RSV-related infection in prophylaxed CMC during the first 3 years of life and (2) assess the burden of illness following RSVH. A single tertiary center, retrospective study, was conducted of CMC who received palivizumab during the 2012-2016 RSV seasons. Fifty-four subjects were enrolled; most received one (38.9%, n = 21) or two (57.4%, n = 31) seasons of prophylaxis (mean = 4.2 [SD = 1.24], palivizumab doses per season). The cohort comprised children with multiple medical conditions (n = 22, 40.8%), tracheostomy (n = 18, 33.3%), and invasive (n = 10, 18.5%) or non-invasive (n = 4, 7.4%) ventilation. Of the CMC, 24 were hospitalized 47 times for a viral-related respiratory illness. RSV incidence in the first 3 years of life was 7.4%. Viral-related RIH and RSVH rates were 44.4% (n = 24/54) and 1.9% (n = 1/54), respectively. Of the four RSV-positive children, one was ventilated for 9 days, two acquired nosocomial RSV that was managed on the ward, and one was discharged home under close complex care supervision. All four RSV-positive cases required additional oxygen during their illness. CMC experience a high viral-related RIH rate and palivizumab likely minimizes RSV-related events and associated morbidities. The efficacy of palivizumab in CMC, especially in those ≤ 3 years, should be prospectively evaluated.

Respiratory syncytial virus (RSV) may cause severe illness in cystic fibrosis (CF) children, but recommendations vary on prophylaxis. CARESS is a prospective registry of children who received palivizumab in 32 Canadian sites from 2005 to 2016. Demographic data were collected at enrollment and respiratory illness-related events recorded monthly. We reviewed respiratory illness hospitalization (RIH) and RSV hospitalization (RSVH) in CF children aged < 24 months versus those prophylaxed for standard indications (SI; prematurity, chronic lung disease [CLD] and congenital heart disease [CHD]), and complex medical disorders (CM). Of 23,228 children analyzed, 19,452 (83.8%) were SI, 3349 (14.4%) were CM, and 427 (1.8%) were CF. CF children were more likely to be Caucasian, heavier at birth and enrollment, and less likely to have a sibling or live in crowded conditions. CF children were similar to the other groups in daycare attendance, history of atopy, and exposure to smoking. RIH incidences were 4.3% (premature), 13.8% CLD, 11.5% CHD, 11.7% CM, and 6.8% CF. RSVH incidence in CF children was similar to that in the SI and CM groups: 1.1, 1.5, and 2.0% groups respectively. Cox regression analyses showed that compared to CF children, the HRs for RSVH in SI (HR 2.0 95% CI 0.5-8.3, p = 0.3) and CM (HR 2.4, 95% CI 0.6-9.8, p = 0.2) did not differ. CF children are equally at risk for RSVH relative to those prophylaxed for other indications. Pending robust evidence from prospective trials, palivizumab could perhaps be considered in the interim, for young CF patients born early during the RSV season with evidence of serious lung disease.

Respiratory syncytial virus (RSV) infection in cystic fibrosis (CF) infants is associated with significant morbidities. This study's objective is to evaluate the effectiveness and adverse events related to palivizumab (PVZ) in CF infants. Data on respiratory-related illness (RIH) and RSV hospitalizations (RSVH) were collected retrospectively in CF infants aged < 2 years in Alberta, Canada, from 2000 to 2017. Logistic regression models were used to compare the odds of RSVH or RIH in PVZ infants from the Canadian registry of palivizumab (CARESS) versus untreated (UPVZ) infants from Alberta, after adjusting for potential confounders. Illness severity was compared between cohorts using χ 2 and t tests. A total of 267 CF infants were included: 183 (PVZ) and 84 (UPVZ). A total of 53.3% were tested for RSV. Fifty-five infants experienced a RIH and 10 had a RSVH. The PVZ cohort experienced similar odds of RSVH but decreased odds of RIH versus UPVZ, adjusting for gestational age, birth weight, birth during RSV peak months, and presence of siblings (Exp(B) = 0.23 [0.11-0.49], p < 0.0005). In RSVH-related subjects, PVZ subjects experienced shorter length of overall stay (LOS; t = 2.39 [df = 7], p = 0.048). In those with a RIH, the PVZ group had shorter overall intensive care unit (t = 3.52 [df = 15], p = 0.003) and hospital LOS (t = 2.11 [df = 52], p = 0.04). No serious adverse events were related to PVZ. The odds of RSVH were similar between groups, but PVZ subjects had decreased odds of RIH. The low number of RSV tests performed may explain the similarity in RSVH rates. Significant differences in LOS may indicate decreased RSVH and RIH illness severity in the PVZ versus UPVZ groups.

Healthy, premature infants ≤35 weeks' gestational age (wGA) are universally recognized to be at an increased risk of perinatal morbidity and mortality. Serious respiratory syncytial virus (RSV) lower respiratory tract infection imposes an additional burden of illness on these infants following hospitalization. Incurred morbidities relative to term infants include longer lengths of hospital stay, admission to intensive care, and need for oxygen and mechanical ventilation, all of which are associated with increased hospital costs. The highest morbidities are experienced by premature infants who are youngest (<3 months' chronological age) and are of lower gestational age. Short- and long-term follow-up indicates that healthy preterm infants both of lower gestational age and who are late preterm have obstructive lung function at baseline, which is further compromised by RSV-related infection during infancy. There is increasing evidence that childhood exposure to an episode of RSV infection may set the stage for an abnormal respiratory function trajectory, which, in adulthood, leads to chronic obstructive pulmonary disease. Healthy premature infants <32 wGA merit RSV prophylaxis based on existing data, whereas moderate- and high-risk preterm infants 32 to 35 wGA should be selectively and cost-effectively targeted for prophylaxis using validated risk scoring tools and country-specific thresholds for funding., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Background: The objective was to develop a risk scoring tool which predicts respiratory syncytial virus hospitalisation (RSVH) in moderate-late preterm infants (32-35 weeks' gestational age) in the Northern Hemisphere., Methods: Risk factors for RSVH were pooled from six observational studies of infants born 32 weeks and 0 days to 35 weeks and 6 days without comorbidity from 2000 to 2014. Of 13 475 infants, 484 had RSVH in the first year of life. Logistic regression was used to identify the most predictive risk factors, based on area under the receiver operating characteristic curve (AUROC). The model was validated internally by 100-fold bootstrapping and externally with data from a seventh observational study. The model coefficients were converted into rounded multipliers, stratified into risk groups, and number needed to treat (NNT) calculated., Results: The risk factors identified in the model included (i) proximity of birth to the RSV season; (ii) second-hand smoke exposure; and (iii) siblings and/or daycare. The AUROC was 0.773 (sensitivity: 68.9%; specificity: 73.0%). The mean AUROC from internal bootstrapping was 0.773. For external validation with data from Ireland, the AUROC was 0.707 using Irish coefficients and 0.681 using source model coefficients. Cut-off scores for RSVH were ≤19 for low- (1.0%), 20-45 for moderate- (3.3%), and 50-56 (9.5%) for high-risk infants. The high-risk group captured 62.0% of RSVHs within 23.6% of the total population (NNT 15.3)., Conclusions: This risk scoring tool has good predictive accuracy and can improve targeting for RSVH prevention in moderate-late preterm infants., (© 2018 Wiley Periodicals, Inc.)

Introduction: Palivizumab is a humanized monoclonal antibody used for respiratory syncytial virus (RSV) prophylaxis. RSV is the primary cause of lower respiratory tract infection in children aged <2 years, and can give rise to high-burden hospitalization and respiratory complications in later life. Adherence to a monthly dosing regimen, both in timing and injection number, is essential to sustain therapeutic levels of palivizumab and maintain protective status. Deviation from the approved dosing schedule may reduce the efficacy of palivizumab and increase the risk of breakthrough RSV infection and hospitalization. Areas covered: There is no standardized definition of adherence to palivizumab treatment. This review addresses the wide variability in defining and reporting adherence to palivizumab prophylaxis across different studies. The review assesses whether a relationship exists in the outcomes reported in studies relative to the monthly adherence protocol as defined in published randomized controlled trials of the efficacy and safety of palivizumab. Expert commentary: Standardized detailed reporting of adherence to palivizumab prophylaxis using consistent definitions will help provide a more robust level of evidence. This information may be important when considering variations in effectiveness, alterations to recommendations and guidelines, and cost-effectiveness of treatment.

Children aged <2 years with chronic lung disease (CLD) have a 10-fold higher risk for respiratory syncytial virus-positive hospitalization (RSVH) compared to healthy term infants. Based on the updated position statements, we compared respiratory-related illness hospitalization (RIH) and RSVH risks in CLD children who received palivizumab during the first year (FY) versus second year (SY) of life in the Canadian Registry of Palivizumab (CARESS). Demographic data were collected at enrolment and RIH events recorded monthly from 2005 to 2015. Eight hundred forty-seven FY and 450 SY children with CLD were identified. SY children had a lower gestational age (27 versus 29 weeks) and required more days of respiratory support (64 versus 43), oxygen therapy (108 versus 55), and length of stay (118 versus 73) during the neonatal course compared to FY children; all p < 0.0005. RIH rates were 12.2 (FY) and 18.2 (SY), and RSVH rates were 2.3 (FY) and 3.9 (SY). Cox regression showed similar hazards for both RIH (hazard ratio 0.9, 95% CI 0.6-1.6, p = 0.812) and RSVH (hazard ratio 1.1, 95% CI 0.4-2.9, p = 0.920)., Conclusions: SY and FY children had similar risks for RIH and RSVH. The findings imply that SY children with CLD are correctly selected for palivizumab based on neonatal illness severity and merit prophylaxis. What is Known: • Children with chronic lung disease have a 10-fold higher risk for RSV-positive hospitalization in comparison to healthy term infants and commonly receive palivizumab prophylaxis as a preventative measure against serious RSV-related lower respiratory tract infections. • The American Academy of Pediatrics [ 2 ] and the Canadian Paediatric Society [ 30 ] have recently modified their recommendations for RSV prophylaxis in children with chronic lung disease, limiting palivizumab to either those <32 weeks gestation or those in the first year of life who are oxygen dependent or require medical therapy for the treatment of their condition. What is New: • Children with chronic lung disease receiving an additional course of palivizumab in their second year of life were determined to be at similar risk for both respiratory illness-related hospitalization and RSV-positive hospitalization as palivizumab-naïve children enrolled in the first year of life in the Canadian Registry for palivizumab (CARESS). • CARESS physicians are correctly identifying high-risk children with chronic lung disease in their second year of life, whom they believe will benefit from an additional year of palivizumab prophylaxis, based on neonatal illness severity.

Background: Moderate-late preterm infants, 33-35 weeks' gestational age (wGA), are at increased risk for respiratory syncytial virus hospitalization (RSVH). The objective of this study is to quantify the burden of RSVH in moderate-late preterm infants., Methods: A pooled analysis was conducted on RSVH from 7 prospective, observational studies in the Northern Hemisphere from 2000 to 2014. Infants' 33-35 wGA without comorbidity born during the respiratory syncytial virus season who did not receive respiratory syncytial virus immunoprophylaxis were enrolled. Data for the first confirmed RSVH during the season (+1 month) were analyzed. Incidence and hospitalization rate per 100 patient-seasons, intensive care unit admission and length of stay (LOS), oxygen support, mechanical ventilation and overall hospital LOS were assessed., Results: The pooled analysis comprised 7,820 infants; 267 experienced a confirmed RSVH at a median age of 8.4 weeks. The crude pooled RSVH incidence rate was 3.41% and the rate per 100 patient-seasons was 4.52. Median hospital LOS was 5.7 days. A total of 22.2% of infants required intensive care unit admission for a median LOS of 8.3 days. A total of 70.4% received supplemental oxygen support for a median of 4.9 days, and 12.7% required mechanical ventilation for a median of 4.8 days., Conclusions: The burden of RSVH in moderate-late, 33-35 weeks' wGA preterm infants without comorbidities born during the viral season in Northern Hemisphere countries is substantial. Severe cases required prolonged and invasive supportive therapy., Competing Interests: Funding support for this pooled database analysis was provided by AbbVie. E.J.A., X.C.-E., M.B., M.L., M.S.-P. and B.P. have received research funding and/or compensation as advisor/lecturer from AbbVie. E.J.A. has received research funding from MedImmune. B.R.-G. and J.F., working for Strategen, have previously received payment from AbbVie for work on various projects. E.R., P.V. and F.C. are former employees of AbbVie and may hold AbbVie stock or stock options. G.N. is an employee of AbbVie and may hold AbbVie stock or stock options. The authors have no conflicts of interest to disclose.

Background: Respiratory syncytial virus (RSV) infection frequently results in RSV-related hospitalization (RSVH) in young infants. We examined the outcomes of palivizumab recipients within the Canadian Registry (CARESS) and the Torino-Verona Italian Registry over the 2002-2014 RSV seasons., Methods: RSVHs were captured during the study seasons. Premature infants who received palivizumab (≤35 completed weeks' gestational age; group1) were compared with infants given palivizumab for underlying disorders regardless of gestational age (group 2). Variables and between-group incidences were analyzed. Risk factors associated with RSVH were assessed by logistic regression., Results: A total of 14,468 palivizumab-exposed infants were enrolled (group 1, n = 9093; group 2, n = 4856; miscellaneous, n = 519). RSVH was significantly more frequent in group 2 (211/4856, 4.34%) versus group 1 infants (216/9093, 2.37% [relative risk 1.93; 95% confidence interval (CI): 1.60-2.33; P < 0.0001]). Infants with neuromuscular disorders (7.88%), airway anomalies (5.95%), bronchopulmonary dysplasia (4.75%) and hemodynamically significant congenital heart disease (4.10%) had the highest RSVH incidences. After multivariable logistic regression, only neuromuscular disease [odds ratio [OR] 4.29; 95% CI: 2.30-8.00; P < 0.01], airway anomalies (OR 3.23; 95% CI: 1.92-5.43; P < 0.01), Down syndrome (OR 2.25; 95% CI: 1.31-3.89; P < 0.01), hemodynamically significant congenital heart disease (OR 2.24; 95% CI: 1.52-3.31; P < 0.001), prematurity ≤28 completed weeks' gestational age (OR 1.82; 95% CI: 1.29-2.58; P < 0.001) and bronchopulmonary dysplasia (OR 1.81; 95% CI: 1.31-2.50; P < 0.001) significantly predicted RSVH. No significant association was detected with the number of doses administered or the time elapsed after the previous dose., Conclusions: RSVH rates are higher in infants given palivizumab for reasons other than prematurity. It is uncertain whether these findings relate to inadequate current palivizumab dosing protocols or to a specific increased RSVH risk inherent in infants with severe underlying comorbidities.

Background: Aboriginal infants are at risk for serious respiratory infection., Objective: To determine the hazard rate (HR) for respiratory-related illness (RIH) and respiratory syncytial virus (RSV) specific infection hospitalization (RSVH) in Aboriginal versus non-Aboriginal children receiving palivizumab and the effect of adherence on hospitalization., Methods: Palivizumab recipients in the Canadian registry from 2005 to 2014 were included. Adherence was determined by the number of palivizumab doses received during the RSV season and interdose time interval. Adherence proportions between groups were compared by χ test. Cox proportional hazard analysis determined the effect of Aboriginal status and adherence on the risk of RIH and RSVH., Results: Aboriginal infants comprised 3.6% (701/19,235) of the registry. HR was 1.6 [95% confidence interval (CI): 1.3-2.0, P < 0.001] and 1.2 (95% CI: 0.7-2.2, P = 0.383) for RIH and RSVH. Aboriginal infants were 62.8% and 63.3% adherent with all recommended injections and within stipulated time intervals, respectively, whereas 81.9% (χ = 162.45, df = 1, P < 0.001) and 72.4% (χ = 27.35, df = 1, P = 0.002) of non-Aboriginal infants were correspondingly adherent. Only 39.9% of Aboriginals were perfectly adherent (adherent to total number and injection intervals), compared with 61.7% of non-Aboriginals (χ = 133.89, df = 1, P < 0.001). Even after adjustment for known risk factors, being Aboriginal and nonadherent was associated with higher RIH hazard (HR = 1.4, 95% CI: 1.1-1.8; HR = 1.3, 95% CI: 1.1-1.4, P = 0.004), respectively. Aboriginals nonadherent with interdose intervals had a 2.2-fold increased HR for RSVH (HR = 2.2, 95% CI: 1.2-4.2, P = 0.015)., Conclusions: Prophylaxed Aboriginal infants have a significantly increased RIH and RSVH hazard than non-Aboriginal infants. Improving adherence especially interdose frequency may further reduce hospitalizations in this vulnerable population.

Background: In several countries, respiratory syncytial virus prophylaxis is offered to late preterm infants who are at escalated risk of respiratory syncytial virus hospitalization (RSVH). However, targeted prophylaxis should be informed by country-specific data. This study, which uniquely includes 36 weeks of gestational age (GA) infants, aims to establish the risk factors for RSVH in 32-36 weeks of GA infants in Ireland., Methods: A prospective observational study at 13 hospitals of laboratory-confirmed RSVH in nonprophylaxed 32-36 weeks of GA infants was conducted from July 2011 to February 2014. Baseline and first-year clinical data were analyzed by using SPSS software Version 22 (IBM Corp, Armonk, NY). Significant (P < 0.05) variables were entered into multiple logistic regression to determine the independent risk factors for RSVH., Results: Sixty-three percent of eligible infants (1825 of 2877) were recruited. The RSVH rate was 3.6% (65 of 1807 analyzed infant records). There was no RSV-attributable mortality. Twelve infants required intensive care. Of the 15 variables correlating to RSVH, 5 independent risk factors were identified: older siblings [odds ratio (OR): 3.8; 95% confidence interval (CI): 1.97-7.41], being Caucasian (OR: 2.3; 95% CI: 1.04-5.29), neonatal respiratory morbidity (OR: 2.2; 95% CI: 1.28-3.94); birth July 15 to December 15 (OR: 2.1; 95% CI: 1.09-3.92) and family history of asthma (OR: 1.9; 95% CI: 1.01-3.39). Birth from 36 weeks to 36 + 6 days mitigated RSVH risk (relative risk: 0.58; 95% CI: 0.34-0.99); however, risk factors were similar to the 32-35 weeks of GA cohort., Conclusion: Neonatal respiratory morbidity or being Caucasian were the population-specific independent risk factors for RSVH in 32-36 weeks of GA in Ireland, whereas the other identified independent risk factors mirrored those established in previous studies.

Background: Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infections in infants. Palivizumab, a means of passive prophylaxis, relies on patient adherence to ensure therapeutic effectiveness. The objective of this study is to evaluate the association between adherence and the incidence of RSV-associated outcomes and to identify demographic factors that may impact adherence., Methods: Infants were recruited into the Canadian registry of palivizumab (CARESS) with parental consent. Monthly interviews collected information on palivizumab administration and RSV-associated outcomes. An infant was considered adherent if they received all of their expected injections or ≥5 injections within the appropriate interdose intervals., Results: Nineteen thousand two hundred thirty-five infants received a total of 83,447 injections from October 2005 to May 2014. Adherence was more likely in infants with higher maternal education and in those with siblings. Adherence was less likely in infants of aboriginal descent, with mothers who smoke and older infants. Adherence was significantly associated [odds ratio (95% confidence interval), P value] with a lower incidence of RSV infection [0.74 (0.60-0.93), 0.01] but not with RSV-associated hospitalization. However, in those hospitalized for RSV, adherence was significantly associated with the incidence of intubation and duration of hospitalization, intensive care stay and respiratory support., Conclusions: Adherence may have implications in children with less severe RSV infections and those who are already hospitalized for a RSV infection. Our study also identifies subpopulations that are more likely to be nonadherent to palivizumab therapy. Future studies should aim to validate the relationship among adherence, palivizumab levels and RSV-associated outcomes.

Objectives: To evaluate the safety and tolerability of palivizumab for RSV prophylaxis in high-risk children in everyday practice., Methods: High-risk children prophylaxed against RSV infection were recruited into a prospective, observational, Canadian RSV Evaluation Study of Palivizumab (CARESS) registry with active, serious adverse event (SAE) monitoring from 2008 to 2013. SAE reports were systematically collected and assessed for severity and relationship to palivizumab. Data were analyzed by Chi-square or Fisher Exact Tests to examine group differences in proportions., Results: 13025 infants received 57392 injections. Hospitalizations for respiratory-related illness (RIH) were reported in 915 patients, and SAEs other than RIH were reported in 52 patients. Of these, 6 (0.05%) patients had a total of 14 hypersensitivity reactions that were deemed possibly or probably related to palivizumab (incidence: 2.8 per 10,000 patient-months). The SAEs of 42 patients were assessed as not related to palivizumab. SAEs in the remaining 4 patients were not classifiable as their records were incomplete. There were no significant demographic predictors of SAE occurrence., Conclusions: Under active surveillance, a small proportion of infants in the CARESS registry experienced SAEs that had a potential relationship with palivizumab and these appeared to be unpredictable in terms of onset. Palivizumab appears to be a safe and well-tolerated antibody for RSV prophylaxis in high-risk children in routine practice.

Several environmental and demographic risk factors have been validated and are used to determine the risk of acquiring severe respiratory syncytial virus (RSV) infection and subsequent hospitalization in late preterm infants born at 33-35 weeks gestational age. The applicability of the same composite model of risk factors in the term population has not been fully explored. The primary objective of this pilot study was to establish whether a risk scoring tool (RST), could predict the severity of RSV infection in term, RSV-positive infants who were hospitalized. A retrospective observational study was conducted in a pediatric unit, over 2 RSV seasons (2011-2013). A convenient sample of 72 children was selected out of a total of 111 RSV-positive cases after exclusions. The RST was applied and a score of respiratory disease severity was determined for each patient. Demographic characteristics were analyzed by standard descriptive methods, χ(2) analysis was utilized for categorical data and ANOVA for comparison between the clinical severity groups and the RST score. A P-value <0.05 was considered significant. Sixty per cent (n = 43) of all infants scored in the low-risk category compared to 26% (n = 19) in the moderate and 14% (n = 10) in the high-risk groups. RST scores were also inconsistent with disease severity. Mean (SD) RST scores for those with mild, moderate, and severe illness were 47.8 [16.4], 41.1 [20.39] and, 41.7 [19.8], respectively (P = 0.17). In conclusion, the RST did not predict accurately the clinical severity of RSV bronchiolitis in term infants nor did it correlate with risk for RSV-related hospitalization., (© 2015 Wiley Periodicals, Inc.)

Premature infants are at substantial risk for a spectrum of morbidities that are gestational age dependent. Respiratory syncytial virus (RSV) infection is most common in the first two years of life with the highest burden in children aged <6 months. Preterm infants ≤35 weeks' gestation are handicapped by incomplete immunological and pulmonary maturation and immature premorbid lung function with the added risk of bronchopulmonary dysplasia. Superimposed RSV infection incites marked neutrophilic airway inflammation and innate immunological responses that further compromise normal airway modeling. This review addresses the epidemiology and burden of RSV disease, focusing on the preterm population. Risk factors that determine RSV-disease severity and hospitalization and the impact on healthcare resource utilization and potential long-term respiratory sequelae are discussed. The importance of disease prevention and the evidence-based rationale for prophylaxis with palivizumab is explored, while awaiting the development of a universal vaccine.

Background and Objectives: Children with Down syndrome (DS) are at significant risk for respiratory syncytial virus (RSV) infection and related hospitalization. We compared hospitalization rates due to respiratory tract infection in children with DS aged <2 years who prospectively received palivizumab during the RSV season with a previously published, similar untreated DS birth cohort., Methods: A total of 532 children with DS who prospectively received palivizumab were assembled from the prospective Canadian RSV Evaluation Study of Palivizumab registry between 2005 and 2012. The untreated group included 233 children with DS derived from a nationwide Dutch birth cohort from 2003 to 2005. Events during the RSV seasons were counted. Poisson regression analysis was performed to compare incidence rate ratios (95% confidence intervals [CIs]) between groups while controlling for observation length and known risk factors for severe RSV infection., Results: In total, 31 (23 untreated, 8 treated) RSV-related hospitalizations were documented. The adjusted risk of RSV-related hospitalizations was higher in untreated subjects than in palivizumab recipients (incidence rate ratio 3.63; 95% CI, 1.52-8.67). The adjusted risk of hospitalization for all respiratory tract infection (147 events; 73 untreated, 74 treated) was similar (incidence rate ratio untreated versus palivizumab 1.11; 95% CI, 0.80-1.55)., Conclusions: These results suggest that palivizumab is associated with a 3.6-fold reduction in the incidence rate ratio for RSV-related hospitalization in children with DS during the first 2 years of life. A randomized trial is needed to determine the efficacy of RSV immunoprophylaxis in this specific high-risk patient population., (Copyright © 2014 by the American Academy of Pediatrics.)

Objectives: To examine the characteristics of congenital heart disease patients hospitalised with respiratory syncytial virus infection after prophylaxis and determine the associated comorbidities and the incidence of breakthrough respiratory syncytial virus infections., Study Design: This is a retrospective, single-centre study that was conducted over a period of 7 years. Respiratory syncytial virus infection was identified by classification codes and confirmed by virological tests. Data on baseline demographics, cardiac anomalies, other underlying disease, criteria for hospitalisation, type of respiratory illness and management, complications, and palivizumab prophylaxis were analysed by standard descriptive methods and comparative statistics., Results: A total of 30 patients were enrolled. The majority were ≤ 2 years (n = 24). The mean admission age was 15.1 months (standard deviation = 18.3). In all, 90% were acyanotic, 40% had haemodynamically significant disease, and 60% had ≥ 1 underlying medical illness. Patients were admitted with: respiratory distress (86.7%), hypoxaemia (66.7%), fever (60%), inability to maintain oral intake (36.7%), and apnoea (16.7%). More than 50% required mechanical ventilation and intensive care with a median stay of 11 days (range: 1-43); the length of hospital stay for all children was 10 days (range: 1-65). Complications included: concurrent bacterial sepsis (20%), electrolyte abnormalities (16.7%), and worsening pulmonary hypertension (13.3%). Of 10 infants ≤ 2 years with haemodynamically significant heart disease, four had received prophylaxis. There was one death, which was attributed to respiratory syncytial virus infection., Conclusions: Overall, 185 infants ≤ 2 years with haemodynamically significant cardiac disease received prophylaxis. In all, six qualifying infants missed immunisation and were hospitalised. Breakthrough respiratory syncytial virus infections occurred in 2.2%, demonstrating good efficacy of palivizumab in this population compared with the original, multi-centre, randomised trial.

Background: Down syndrome (DS) is a risk factor for respiratory syncytial virus (RSV) hospitalization, but little is known about prophylaxis in these children., Methods: CARESS is a prospective registry of children who received ≥1 dose of palivizumab during the 2006-2012 RSV seasons across 32 sites in Canada. The objective was to compare respiratory illness hospitalization and RSV hospitalization (RSVH) hazard ratios in DS children aged <2 years who received palivizumab versus children who received prophylaxis for standard indications (SI) and for other medical illnesses (MI)., Results: 13,310 children were enrolled; DS (600; 4.5%), SI (11,081; 83.3%) and MI (1629, 12.2%), with DS children increasing over the duration from 0.1% (2006) to 4.5% (2012). Participants were significantly different in mean birth weight, gestational and enrollment age and risk factors. Children in each group received an average of 4.3 ± 1.4 (DS), 4.1 ± 1.6 (SI) and 4.5 ± 1.4 (MI) palivizumab injections per RSV season, with DS, differing significantly from SI [F(2, 13,307) = 43.6, P = 0.01] but not MI [F(2, 13 307) = 43.6, P = 0.07]. Compliance rates were similar across the groups. While a significantly greater proportion of SI children had RIHs compared with DS, [hazard ratio: 0.64 (0.48-0.84); P = 0.001] hazard ratios were similar for DS and MI. RSVH incidence rates were: 1.53%, 1.45% and 2.27% for DS, SI and MI, respectively. Neither group nor compliance affected time to RSVH., Conclusions: The proportion of DS children who received palivizumab in CARESS has increased almost 45-fold. RSVH rates were low in DS following prophylaxis and hazards were similar to those found in SI and MI.

Respiratory syncytial virus (RSV) infection occurs commonly in infants aged ≤2 years, and severe infection results in hospitalization with accompanying morbidity and mortality. Palivizumab has been available for prophylaxis for the past 15 years. Prospective data on patients who received palivizumab from 2005 to 2012 has been assembled in the Canadian registry (CARESS) to document utilization, compliance, and health outcomes in both hospital and community settings. Long-term data is necessary to evaluate the impact of palivizumab on the incidence of RSV infections, minimize healthcare resources, and identify which infant subpopulations are receiving prophylaxis. A database search was also conducted for similar information from published registries, and hospitalization rates were compared to results from randomized clinical trials (RCTs).Overall hospitalization rates (percent; range) for respiratory-related illnesses and RSV-specific infection in infants who meet standard indications for prophylaxis were 6.6 (3.3-7.7) and 1.55 (0.3-2.06), respectively, in CARESS, which closely aligns with registry data from 4 other countries, despite the former comprising the largest cohort of complex patients internationally. Overall RSV-related hospitalization rates were lower across registries compared to equivalent patients in RCTs. Registry data provides valuable information regarding real-world experience with palivizumab, while facilitating the genesis of new research themes.

Objective: To review and summarize the literature concerning the cost-effectiveness of palivizumab compared to no prophylaxis in infants and young children with congenital heart disease (CHD)., Methods: A systematic literature search (MEDLINE to March 2012, limited to English language) identified studies that examined the cost-effectiveness of palivizumab in CHD populations. The quality of each study was assigned a quality score of 1-100 based on the Quality of Health Economic Studies (QHES) instrument., Results: Ten studies were identified through the search strategy, of which four principally addressed the research question and six additional articles examined CHD in conjunction with other high-risk indications for palivizumab in their economic analyses. QHES for the studies ranged from 58-100, with a median score of 93 (76 for principal articles, 94 for secondary analyses). Cost-utility analyses, which evaluated costs per quality-adjusted life year (QALY), showed favorable results in five analyses (range $10,329-$16,648 per QALY), while the other two suggested no cost-effectiveness ($146,061 and $169,971 per QALY). Of three cost-effectiveness analyses, which assessed costs per hospital admission prevented (HAP), two concluded that the drug was not cost-effective ($16,216/day of hospitalization prevented and $868,296/HAP), while one did not interpret the final result ($43,561/HAP)., Limitations: Significant variance exists across study characteristics, analytic models utilized, duration of RSV seasons assessed, primary outcome measures evaluated, sensitivity analyses conducted, and other model assumptions. Further, it was difficult to obtain true CHD-based quality scores for the studies that analyzed more than one indication., Conclusions: The findings of this review currently remain inconclusive. Although a favorable trend was identified in the cost-utility analyses, additional rigorously conducted studies are necessary to better estimate the cost-effectiveness of palivizumab for CHD infants in clinical practice.

Prospective cohort studies show that Down's syndrome (DS) is an independent risk factor for hospitalization for RSV bronchiolitis. It is unknown whether this observation has been translated into specific management for DS children. The primary goal was to assess the knowledge of healthcare providers in the European Union about RSV infection in DS children and to determine whether it influenced the implementation of prophylaxis. DS caregivers were surveyed using a standardized questionnaire, and country-specific guidelines were obtained. Fifty-three caregivers participated. Thirty-nine (86.7%) had knowledge of the increased risk of severe RSV infection in DS children, and 30 (71.4%) graded that it was important to have a statement on the use of RSV prophylaxis in existing guidelines. Twenty-eight participants had a local DS guideline; hard copies of twelve unique guidelines were obtained. Only one (8.3%) contained a statement on RSV prophylaxis for DS, and five considered such a statement for the next version. Conclusion. Most pediatricians had knowledge that DS children have an increased risk of severe RSV infection. Despite the lack of a specific RSV prophylaxis trial in DS, they felt that a statement on RSV prophylaxis in DS guidelines was important, but this was rarely present in current guidelines.

Health care staff and families with young children are often unware of the ease of respiratory syncytial virus (RSV) spread and potential clinical consequences of serious respiratory illness. Successful Canadian RSV prophylaxis (RSVP) programs (a) provide practical educational resources on RSV and respiratory disease that consider language and cultural barriers; (b) develop policies to identify all children eligible for RSVP with palivizumab; (c) emphasize compliance with RSVP, particularly during patient transfer between hospitals, community clinics, and remote outpost centers; and (d) establish collaborative networks to help ensure optimum RSVP compliance for all high-risk children. Herein, we share practical resources and key educational references for counseling of caregivers with infants or young children at risk for RSV infection, and health care providers participating in RSVP program development.

Globally, respiratory syncytial virus (RSV) infection causes substantial morbidity in infants and young children, particularly those with specific risk factors (e.g., prematurity, chronic lung and congenital heart disease). Supportive measures are the mainstay of care for RSV-related disease. In the absence of medical treatments, RSV prophylaxis (RSVP) with palivizumab is recommended for high-risk patients to help reduce the risk of developing serious disease. Geographic distances, language and cultural barriers, and other factors can impede effective education of caregivers regarding the potential impact of RSV disease and benefits of RSVP compliance. We present our experiences developing successful Canadian RSVP programs, organized through a dedicated coordinator or small group of health care staff. These programs focus on identifying all infants and young children eligible for RSVP, effectively educating health care staff and family caregivers, developing educational tools that consider language and cultural factors, and interdisciplinary collaboration and networking throughout the health care system.

Respiratory syncytial virus (RSV) infections are prevalent globally and can cause substantial morbidity in infants and young children. The virus is easily transmitted by direct hand-to-hand contact and can lead to serious respiratory disease and hospitalization, particularly in premature infants and children with certain medical conditions. Educating families with young children, especially those in remote rural regions, regarding the potential adverse health outcomes of RSV infection and measures to reduce the risk of transmitting or acquiring RSV has been a key focus of the health care system in Canada. Geographic, cultural, and socioeconomic factors present formidable challenges to the execution of this endeavor. Therefore, it is critical to develop and systematically implement effective educational programs for both families and health care providers. In Canada, nurses play a critical role in education and counseling. In this review, we share our perspectives and suggest empirical practices that may be applicable worldwide.

We examined the dosing regimens, compliance, and outcomes of premature infants who received palivizumab within the Canadian Registry of Palivizumab (CARESS). Infants receiving ≥1 dose of palivizumab during the 2006-2011 respiratory syncytial virus (RSV) seasons were recruited across 30 sites. Respiratory illness events were captured monthly. Infants ≤32 completed weeks gestational age (GA) (Group 1) were compared to 33-35 completed weeks GA infants (Group 2) following prophylaxis. In total, 6,654 patients were analyzed (Group 1, n = 5,183; Group 2, n = 1,471). The mean GA was 29.9 ± 2.9 versus 34.2 ± 2.2 weeks for Groups 1 and 2, respectively. Group differences were significant (all p-values <0.05) for the following: proportion of males, Caucasians, siblings, multiple births, maternal smoking, smoking during pregnancy, household smokers, >5 household individuals, birth weight, and enrolment age. Overall, infants received 92.6 % of expected injections. Group 1 received significantly more injections, but a greater proportion of Group 2 received injections within recommended intervals. The hospitalization rates were similar for Groups 1 and 2 for respiratory illness (4.7 % vs. 3.7 %, p = 0.1) and RSV (1.5 % vs. 1.4 %, p = 0.3). Neither the time to first respiratory illness [hazard ratio = 0.9, 95 % confidence interval (CI) 0.7-1.2, p = 0.5] nor to first RSV hospitalization (hazard ratio = 1.3, 95 % CI 0.8-2.2, p = 0.3) were different. Compliance with RSV prophylaxis is high. Despite the higher number of palivizumab doses in infants ≤32 completed weeks GA, the two groups' respiratory illness and RSV-positive hospitalization rates were similar.

Palivizumab prophylaxis has been demonstrated to reduce the number of hospitalizations attributable to respiratory syncytial virus in high-risk infants. However, as palivizumab acquisition costs are high, quantifying cost-effectiveness is important. The primary aim of this review was to examine the cost-effectiveness of palivizumab across numerous indications in high-risk infants and to report on factors that may impact outcomes. A systematic literature search was conducted to identify pharmacoeconomic analyzes of palivizumab compared to no prophylaxis for respiratory syncytial virus in infants and young children. A total of 28 articles met inclusion criteria and were subsequently assigned quality scores according to the Quality of Health Economic Studies criteria. Results varied according to perspective, input parameters, outcome measures, populations and base-case and sensitivity analyses. Overall, cost-effectiveness results were inconsistent. Some studies reported favorable outcomes, while others did not, or were inconclusive. Factors to consider in the interpretation of such economic evaluations are discussed.

Palivizumab utilization, compliance, and outcomes were examined in infants with preexisting medical diseases within the Canadian Registry Database (CARESS) to aid in developing guidelines for potential "at-risk" infants in the future. Infants who received ≥1 dose of palivizumab during the 2006-2010 respiratory syncytial virus (RSV) seasons at 29 sites were recruited and utilization, compliance, and outcomes related to respiratory infection/illness (RI) events were collected monthly. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated for premature infants ≤35 completed weeks gestational age (GA) who met standard approval criteria (group 1) compared to those with medical disorders (group 2) using Cox proportional hazards regression models with adjustment for potential confounding factors. Of 7,339 registry infants, 4,880 were in group 1 and 952 in group 2, which included those with Down syndrome (20.3%), upper airway anomalies (18.7%), pulmonary diseases (13.3%), and cystic fibrosis (12.3%). Group 2 were older at enrollment (10.2 ± 9.2 vs. 3.5 ± 3.1 months, p < 0.0005), had higher GA (35.9 ± 6.0 vs. 31.0 ± 5.4 weeks, p < 0.0005), and were less compliant with treatment intervals (69.4% vs. 72.6%, p = 0.048). A greater proportion of group 2 infants were hospitalized for RI (9.0% vs. 4.2%, p < 0.0005) and RSV (2.4% vs. 1.3%, p = 0.003) (unadjusted). Being in group 2 was associated with an increased risk of RI (HR = 2.0, 95%CI 1.5-2.5, p < 0.0005), but not RSV hospitalization (HR = 1.6, 95% CI 0.9-2.8, p = 0.106). In infants receiving palivizumab, those with underlying medical disorders, though not currently approved for prophylaxis, are at higher risk for RI events compared with preterm infants. However, risk of RSV hospitalizations is similar.

Respiratory syncytial virus (RSV) is the most frequent aetiologic agent that causes bronchiolitis and lower respiratory tract infection in infants. These infections may be severe and even life-threatening in selected high-risk populations. Traditional, well-established, high-risk populations are preterm infants with or without chronic lung disease and children with congenital heart disease. For these children, RSV prophylaxis using palivizumab, a monoclonal anti-RSV humanised antibody against the F-protein of RSV, has proven safe and efficacious in preventing RSV-related hospitalisation. Recently, a number of rare medical conditions have been associated with the risk of severe RSV infections. Evidence of safety and efficacy of RSV prophylaxis in these populations is lacking. Given the low incidence of these conditions, randomised trials are not feasible. A practical, opinion-based approach to this dilemma is offered in this paper. It is proposed that these rare disorders may qualify for RSV prophylaxis if the association between a specific condition and the risk of severe RSV infection is confirmed in at least 3 independent publications, of which at least 1 includes a prospective cohort study. To facilitate pharmaco-economic analyses, at least one of the three studies must also report on the absolute risk of severe RSV infection in the specified illness. The authors believe that qualification criteria will enable caregivers to target RSV prophylaxis more effectively in children with rare conditions and the proposed approach provides direction for future epidemiological studies on the risk of severe RSV infection in children with these uncommon, medical illnesses., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Congenital abnormalities and impaired mechanisms that govern the normal coordinated physiology of breathing, sucking, swallowing and airway clearance, place infants with underlying medical disorders at high risk for respiratory morbidity following respiratory syncytial virus (RSV) lower respiratory tract infection. The use of RSV prophylaxis in premature infants' ≤ 35 weeks gestational age, infants with chronic lung and hemodynamically significant heart disease is firmly established through randomized controlled clinical trials (RCT's). RSV prophylaxis in infants with serious medical illnesses must be justified based on emerging scientific literature and the overriding concept of achieving a balance between benefit and harm with treatment. This article will explore the current evidence for palivizumab prophylaxis in a variety of disorders and examine existing differences between pediatric advisory body recommendations and real world practice., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Preterm infants are at increased risk of being rehospitalised during the first few months of life with severe respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) that usually manifests as apnea and hypoxemia. This occurs more commonly in preterm infants < 33 weeks gestational age (GA), but recent studies demonstrate that late preterm infants (those born between 34 weeks and 0 days to 36 weeks and 6 days GA) are equally susceptible to RSV LRTI as those with lower GA. Factors associated with severe LRTI include immaturity of both the humoral and cell-mediated immune system and interrupted lung development prior to 36 weeks GA which results in lower functional residual capacity, reduced compliance, diminished forced expiratory air flow and impaired gas exchange. Morbidity and mortality are significantly increased in late preterms compared to their term counterparts. Prophylaxis with palivizumab against RSV infection seems to be crucial. Due to the large number of infants in this age group, additional risk factors have been identified in order to tailor palivizumab prophylaxis effectively to those at highest risk for severe RSV LRTI., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: Palivizumab prophylaxis against respiratory syncytial virus (RSV) infection has been widely adopted for high-risk infants during the RSV season, based on country-specific guidelines., Objective: To determine if a validated, risk-scoring tool (RST), can be applied to term, RSV-positive infants seen in the emergency room (ER) to predict need for hospitalization, in order to target prophylaxis cost effectively at a selected group of children., Design: Retrospective, descriptive study., Setting: McMaster Children's Hospital in Hamilton, Ontario, Canada., Participants: A total of 72, consecutive, term, RSV-positive cases were identified retrospectively, from November through April during the 2006-2007 RSV season., Methods: A questionnaire/chart review was conducted on 68 of 72 cases, to determine risk categories based on the RST. Four, trained abstractors, extracted pertinent data from the medical records of RSV-positive patients. Means, standard deviations (SD), and percents were used to describe the study variables for hospitalized and ER patients discharged home. Chi-square tests were used to compare infants' risk factors to hospitalization. ANOVA was used for comparisons within and between risk groups and RST scores. A p-value of <0.05 was considered statistically significant., Results: The majority of infants scored in the low-risk category (n = 44), versus moderate (n = 16) or high risk (n = 8). Within the low-risk category, 27 (61%) of children were admitted to hospital compared to 17 (39%) who were treated in the ER and discharged home. The mean RST scores for those admitted to the pediatric intensive care unit/ward, the ward only, or those discharged home from the ER were 48.3 (n = 10), 41.0 (n = 36), and 36.5 (n = 22), respectively (p = 0.17). The mean number of risk factors for those discharged home versus hospitalized patients was 2.5 (1.3) and 2.97 (1.13), respectively (p = 0.15). Only two of eight cases in the high-risk group required intensive care., Conclusions: Overall, the risk-scoring tool did not discriminate between low versus moderate- to high-risk RSV-positive term infants who require hospitalization which has cost implications, since universal prophylaxis of this cohort would be financially prohibitive. A larger study is necessary to establish risk factors that more accurately determine RSV hospitalization among term infants.

Objective: To study the impact of the Risk-Scoring Tool (RST) as a strategy for targeting prophylaxis effectively in 33-35-week gestational age (GA) Canadian infants who range from low to high risk by evaluating the subsequent incidence of respiratory syncytial virus (RSV) infections resulting in emergency room (ER) visits and hospitalization., Design: Prospective, descriptive study., Setting: McMaster Children's Hospital and St Joseph's Healthcare in Hamilton, Ontario., Participants: Premature infants between 33 and 35 weeks' completed gestation who were less than 6 months' chronological age at the start of, or during, the local 2005-2008 RSV winter seasons., Methods: A validated, Canadian RST was used to calculate a total risk score based on seven risk factors. Only infants at moderate (RST score 49-64) and high risk (RST score 65-100) received palivizumab at monthly intervals from November to April and were followed during the respective RSV seasons. All parents received information on RSV prevention at hospital discharge. Parents of all recruited infants were contacted by telephone in May at the end of each season, and medical records were checked to determine ER visits for RSV-related respiratory tract infections and RSV hospitalization. Means, standard deviations, ranges, and percents were used to describe the variables for patients enrolled in the study., Results: Over 3 years, 430 infants were recruited. Of these, 346 (81%), 57 (13%), and 27 (6%) were in the low-, moderate- and high-risk categories, respectively, based on their risk scores. A total of 78 (18.1%) infants received full courses of palivizumab. Six out of 57 (10.5%) infants in the moderate-risk group did not receive prophylaxis, while all 27 high-risk group infants received palivizumab. Seven (1.6%) infants were RSV-positive and five (low-risk) infants were hospitalized. One high-risk, RSV-positive infant, was seen in the ER, and discharged home. There were no statistical differences in the number of infants with RSV-related ER visits and hospitalizations within the risk category groups (p = 0.43). The limitations of this study include the observational design and the relatively small sample size., Conclusions: The RST is a practical, easy-to-use instrument to guide judicious RSV prophylaxis for moderate-high-risk, 33-35-week GA infants. It is cost-effective, reducing hospitalization in infants who are most 'at-risk', while avoiding prophylaxis in a large segment (81.9%) of this GA cohort who are considered low risk for RSV infection.

Objective: The purpose of the study was to develop and validate a clinical instrument predicting the risk of respiratory syncytial virus (RSV)-associated hospitalization (RSV-H) in premature infants born at 33 through 35 completed weeks of gestation (33-35GA)., Design: An RSV risk scoring tool (RSV-RS) was developed by entering risk factors for RSV-H, determined in a Canadian prospective study, into a multiple logistic regression model. The scoring tool was then validated externally with data from a Spanish case-control study (FLIP). The Canadian cohort comprised 1758 RSV-positive infants born 33-35GA, of whom 66 (3.7%) had confirmed RSV-H. The FLIP data set comprised 186 (33.4%) RSV-H cases and 371 (66.7%) controls., Method: The primary outcome measure was RSV-H. The RSV-RS score was the sum of the weighted probabilities for each included risk factor multiplied by 100 and ranged from 0 to 100. Receiver operator characteristic curve analyses determined cutoff points to predict subjects at low, moderate, or high RSV-H risk., Results: The RSV-RS included 7 risk factors and cutoff scores of 0-48, 49-64, and 65- 100 for low-, moderate-, and high-risk subjects, respectively. For the Canadian cohort, RSV-RS sensitivity in predicting RSV-H cases was 68.2%, with 71.9% specificity. With the FLIP data set, the RSV-RS had lower accuracy (61.3% sensitivity; 65.8% specificity) but showed significant positive association with increased risk for RSV-H., Conclusion: The RSV-RS accurately identified 33-35GA infants at increased risk for RSV-H in a Canadian cohort. External validation with Spanish case-control study data further confirmed that the scoring tool is appropriate for the estimation of RSV-H risk.