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American Family Physician Jun 2024
Topics: Humans; Respiratory Syncytial Virus Infections; Antiviral Agents; Antibodies, Monoclonal, Humanized; Infant; Palivizumab; Viral Vaccines; Respiratory Syncytial Virus Vaccines
PubMed: 38905561
DOI: No ID Found -
JAMA Network Open Jun 2024Respiratory syncytial virus (RSV) transmission was disrupted worldwide following the COVID-19 pandemic, and further study is required to better understand these changes.
IMPORTANCE
Respiratory syncytial virus (RSV) transmission was disrupted worldwide following the COVID-19 pandemic, and further study is required to better understand these changes.
OBJECTIVE
To compare observed and expected RSV hospital and intensive care unit (ICU) admission rates and characteristics of admitted children during the 2021-2022 and 2022-2023 seasons.
DESIGN, SETTING, AND PARTICIPANTS
A population-based cohort study of all children aged younger than 5 years in Ontario, Canada, July 1, 2017, through March 31, 2023, was conducted.
EXPOSURES
Individual and neighborhood-level sociodemographic and clinical characteristics were identified from administrative data, including age, palivizumab eligibility, complex medical conditions, rurality, and living in a marginalized neighborhood.
MAIN OUTCOMES AND MEASURES
The main outcome was RSV-associated hospitalization. Secondary outcomes included ICU admissions, mechanical ventilation, extracorporeal membrane oxygenation, and in-hospital death. Poisson generalized estimating equations were used to model weekly age- and sex-specific hospitalization rates and estimate expected rates in the postpandemic era; adjusted rate ratios (RRs) and 95% CIs are reported.
RESULTS
This cohort study included approximately 700 000 children per study year. Compared with prepandemic years (2017-2018, 2018-2019, and 2019-2020), the 2021-2022 RSV season peaked slightly earlier, but overall admission rates were comparable (289.1 vs 281.4-334.6 per 100 000, or approximately 2000 admissions). The 2022-2023 season peaked a month earlier and resulted in more than twice as many hospitalizations (770.0 per 100 000; n = 4977 admissions). The proportion of children admitted to an ICU in 2022-2023 (13.9%) was slightly higher than prepandemic (9.6%-11.4%); however, the population-based rate was triple the prepandemic levels (106.9 vs 27.6-36.6 per 100 000 children in Ontario). With the exception of palivizumab-eligible children, all sociodemographic and health status characteristics were associated with lower-than-expected RSV hospitalization rates in 2021-2022. In contrast, older age of patients was associated with higher-than-expected rates in 2022-2023 (ie, 24-59 months: RR, 1.90; 95% CI, 1.35-2.66).
CONCLUSIONS AND RELEVANCE
There were notable differences in RSV epidemiologic characteristics in Ontario following the COVID-19 pandemic. It is not yet clear whether and how long atypical RSV epidemics may persist. Clinicians and program planners should consider the potential for ongoing impacts to health care capacity and RSV immunization programs.
Topics: Humans; Respiratory Syncytial Virus Infections; Hospitalization; Infant; Male; Female; Child, Preschool; Ontario; COVID-19; SARS-CoV-2; Intensive Care Units; Cohort Studies; Infant, Newborn; Respiration, Artificial; Pandemics; Palivizumab
PubMed: 38861259
DOI: 10.1001/jamanetworkopen.2024.16077 -
Signal Transduction and Targeted Therapy Jun 2024Respiratory syncytial virus (RSV) is the major cause of bronchiolitis and pneumonia in young children and the elderly. There are currently no approved RSV-specific...
Respiratory syncytial virus (RSV) is the major cause of bronchiolitis and pneumonia in young children and the elderly. There are currently no approved RSV-specific therapeutic small molecules available. Using high-throughput antiviral screening, we identified an oral drug, the prenylation inhibitor lonafarnib, which showed potent inhibition of the RSV fusion process. Lonafarnib exhibited antiviral activity against both the RSV A and B genotypes and showed low cytotoxicity in HEp-2 and human primary bronchial epithelial cells (HBEC). Time-of-addition and pseudovirus assays demonstrated that lonafarnib inhibits RSV entry, but has farnesyltransferase-independent antiviral efficacy. Cryo-electron microscopy revealed that lonafarnib binds to a triple-symmetric pocket within the central cavity of the RSV F metastable pre-fusion conformation. Mutants at the RSV F sites interacting with lonafarnib showed resistance to lonafarnib but remained fully sensitive to the neutralizing monoclonal antibody palivizumab. Furthermore, lonafarnib dose-dependently reduced the replication of RSV in BALB/c mice. Collectively, lonafarnib could be a potential fusion inhibitor for RSV infection.
Topics: Humans; Respiratory Syncytial Virus Infections; Pyridines; Mice; Animals; Respiratory Syncytial Virus, Human; Viral Fusion Proteins; Farnesyltranstransferase; Antiviral Agents; Piperidines; Mice, Inbred BALB C; Protein Conformation; Dibenzocycloheptenes
PubMed: 38853183
DOI: 10.1038/s41392-024-01858-5 -
Infectious Diseases and Therapy Jun 2024Respiratory syncytial virus (RSV) is one of the major causes of respiratory tract infections among children. Until recently, the monoclonal antibody palivizumab was the...
INTRODUCTION
Respiratory syncytial virus (RSV) is one of the major causes of respiratory tract infections among children. Until recently, the monoclonal antibody palivizumab was the only RSV prophylaxis available in Japan. In 2024, the bivalent RSV prefusion F protein-based (RSVpreF) vaccine was approved for the prevention of RSV infection in infants by active immunization of pregnant women. In this study, we assessed the cost-effectiveness of a combined strategy of RSVpreF vaccine and palivizumab in Japanese setting.
METHODS
Using a Markov model, we evaluated prevented cases and deaths of medically attended RSV infections from birth to age 11 months for each of the three healthcare settings: inpatient (hospitalization), emergency department visits, and outpatient visits. Incremental cost-effectiveness ratios (ICERs) were calculated from economic outcomes (intervention costs, medication costs, and productivity losses) and quality-adjusted life years (QALYs). Further, we calculated the maximum price of RSVpreF vaccine within which the program would be cost-effective.
RESULTS
In comparison with the current prophylaxis (palivizumab alone), a combined prophylaxis of year-round RSVpreF vaccination of pregnant women and palivizumab prescription for premature infants born in < 32 weeks gestational age (wGA) and all infants with high risk prevented 14,382 medically attended cases of RSV (hospitalization, 7490 cases; emergency department, 2239 cases; outpatient, 4653 cases) and 7 deaths, respectively. From a healthcare payer perspective, when the price of RSVpreF vaccine was equal to or less than ¥23,948 (US $182), a combination prophylaxis was cost-effective under the ICER threshold of ¥5 million per QALY. The other combination prophylaxis of year-round RSVpreF vaccination and palivizumab prescription of premature born in < 32 wGA regardless of risk in infants was a dominant strategy (more effective and less costly).
CONCLUSION
A combined prophylaxis of year-round RSVpreF vaccine and palivizumab could be a cost-effective strategy to protect neonates throughout the infant stage (< 1 years old) in Japan.
PubMed: 38834858
DOI: 10.1007/s40121-024-01000-6 -
JAMA Jun 2024
Topics: Humans; Respiratory Syncytial Virus Infections; Antiviral Agents; Infant; Palivizumab
PubMed: 38814625
DOI: 10.1001/jama.2024.7406 -
The Turkish Journal of Pediatrics May 2024Respiratory syncytial virus (RSV) is one of the most common pathogens causing severe lower respiratory tract disease in infancy and childhood. In newborns, young...
BACKGROUND
Respiratory syncytial virus (RSV) is one of the most common pathogens causing severe lower respiratory tract disease in infancy and childhood. In newborns, young infants, and in infants with co-morbidities, the risk of severe infection is increased. Current protection against severe RSV infection is immunoprophylaxis with the monoclonal antibody palivizumab. The study aimed to assess the effects of palivizumab prophylaxis in the Republic of Montenegro in comparison to the pre-prophylaxis period.
METHODS
The study was conducted in prospective/retrospective single center format in Montenegro in the Clinical Center of Podgorica, for the period 2009-2019.
RESULTS
A total of 104 high-risk infants in the palivizumab prophylaxis program (2014-2019 RSV seasons) and 168 high-risk children without palivizumab prophylaxis (2009-2013 RSV seasons) were enrolled. A total of 51 children (49.0%) received prophylaxis for prematurity, 33 (31.7%) for bronchopulmonary dysplasia (BPD), 13 (12.5%) for hemodynamically significant heart disease/defect (HSCHD), and 7 (6.8%) for "miscellaneous" indications. In the control group most children had prematurity (101, 60.1%), followed by BPD (59, 35.1%), HSCHD (3, 1.8%), and "miscellaneous" (5, 3.4%) conditions. Readmission to the pediatric intensive care units (PICU) due to RSV infection was significantly lower in prophylaxis group (0.0 vs 16.1%, p<0.001). No lethal outcomes were observed in high-risk children with palivizumab prophylaxis compared to 2.4% in the control group.
CONCLUSIONS
The introduction of RSV immunoprophylaxis as well as other new protective treatment strategies for high-risk newborns led to significant improvements in infant and childcare in Montenegro. This is the first report on palivizumab prophylaxis in Montenegro, demonstrating the effectiveness and safety of palivizumab use in clinical settings.
Topics: Palivizumab; Humans; Respiratory Syncytial Virus Infections; Antiviral Agents; Male; Infant; Female; Infant, Newborn; Prospective Studies; Retrospective Studies; Montenegro; Infant, Premature
PubMed: 38814297
DOI: 10.24953/turkjpediatr.2024.4592 -
MMW Fortschritte Der Medizin Jun 2024
Topics: Humans; Respiratory Syncytial Virus Infections; Infant; Infant, Newborn; Antiviral Agents; Palivizumab; Antibodies, Monoclonal, Humanized; Respiratory Syncytial Virus Vaccines
PubMed: 38806929
DOI: 10.1007/s15006-024-3993-1 -
Pediatric Pulmonology May 2024The aim was to gather an overview of the evidence of monoclonal antibody therapies in respiratory syncytial virus (RSV) prophylaxis in children. For this umbrella review... (Review)
Review
The aim was to gather an overview of the evidence of monoclonal antibody therapies in respiratory syncytial virus (RSV) prophylaxis in children. For this umbrella review of previous meta-analyses, we searched PubMed, Scopus, and Web of Science databases in August 2023. We included systematic reviews with meta-analyses of randomized controlled trials. One author extracted the data, and another author validated the data. We extracted all analyses focusing on clinical outcomes and comparing prophylaxis to placebo. Risk of bias in systematic reviews (ROBIS) tool was used to analyze the risk of bias in the included reviews. AMSTAR-2 was used to evaluate the quality of the included reviews. After screening of 323 abstracts and 22 full reports, a total of seven systematic reviews with meta-analyses were included. The risk of bias was rated to be low in four and high in three of these. Three reviews were of moderate quality, one low, and three very low quality according to AMSTAR-2 classification. Six of the meta-analyses were direct comparisons, and one was a network meta-analysis. Five of the reviews focused on palivizumab, one in nirsevimab, and one included all monoclonal antibodies. Six reviews focused on preterm neonates and consisted of 42 comparisons to placebo of which 21 showed efficacy, and 21 had no evidence of a difference. The positive effect was seen in all reviews against RSV infection and RSV hospitalization in palivizumab and nirsevimab groups compared to placebo. None of the mortality comparisons showed efficacy. One meta-analysis focused on cystic fibrosis patients and had eight comparisons, but it was underpowered to detect any results. The overall evidence from previous meta-analyses shows that monoclonal antibodies are effective in preventing RSV infections and RSV hospitalizations in preterm infants. However, no effect on mortality was seen in these studies. Evidence certainty has been ranked mainly from low to moderate.
PubMed: 38751021
DOI: 10.1002/ppul.27041 -
Human Vaccines & Immunotherapeutics Dec 2024Nirsevimab has been recently licensed for universal RSV prophylaxis in infants. NIRSE-GAL is a three-year population-based study initiated in Galicia in September 2023....
Assessment of effectiveness and impact of universal prophylaxis with nirsevimab for prevention of hospitalizations due to respiratory syncytial virus in infants. The NIRSE-GAL study protocol.
Nirsevimab has been recently licensed for universal RSV prophylaxis in infants. NIRSE-GAL is a three-year population-based study initiated in Galicia in September 2023. It aims to evaluate nirsevimab effectiveness against RSV-related hospitalizations lower respiratory tract infections (LRTI), severe RSV, all-cause LRTI, and all-cause hospitalization. NIRSE-GAL also aims to estimate nirsevimab impact on primary healthcare use in the short and mid-term, children's wheezing and asthma, and medical prescriptions for RSV. The immunization campaigns will be scheduled based on the expected start week for the RSV season and will last the whole season. Immunization will be offered to: i) infants born during the campaign (seasonal), ii) infants < 6 months at the start of the campaign (catch-up), and iii) infants with high-risk factors, aged 6-24 months at the start of the campaign (high-risk). The follow-up period will start: i) the immunization date for all immunized infants, ii) the start of the campaign, for the non-immunized catch-up or high-risk groups, or iii) the birthdate for the non-immunized seasonal group. Infants will be followed up until outcome occurrence, death, or end of study. Nirsevimab effectiveness will be estimated using Poisson and Cox regression models. Sensitivity and stratified analyses will be undertaken. The number of averted cases and the number needed to immunize will be estimated. Immunization failure and nirsevimab safety will be monitored. NIRSE-GAL was approved by the ethics committee of Galicia (CEIC 2023-377) and registered in ClinicalTrials.gov (ID: NCT06180993). Findings will be mainly shared via peer-reviewed publications and scientific conferences.
Topics: Humans; Respiratory Syncytial Virus Infections; Infant; Hospitalization; Antiviral Agents; Respiratory Syncytial Virus, Human; Female; Male; Respiratory Tract Infections; Immunization Programs; Infant, Newborn; Child, Preschool; Palivizumab; Antibodies, Monoclonal, Humanized
PubMed: 38738683
DOI: 10.1080/21645515.2024.2348135 -
Cardiology in the Young Apr 2024Adherence to palivizumab prophylaxis programmes is crucial to protect infants with CHD against respiratory syncytial virus infections. We analysed the effectiveness of...
OBJECTIVES
Adherence to palivizumab prophylaxis programmes is crucial to protect infants with CHD against respiratory syncytial virus infections. We analysed the effectiveness of two nudge interventions in increasing adherence.
METHODS
Our study included 229 infants, and their caregivers, from five centers in Turkey in the 2020-2021 respiratory syncytial virus season. We randomly allocated caregivers to a control and two intervention groups. Caregivers in all groups were informed about the prophylaxis programme and provided a schedule. Additionally, caregivers in Intervention 1 were called two days before appointments (default bias) and were asked to plan the appointment day (implementation intention), whereas caregivers in Intervention 2 received biweekly text messages informing them about the programme's benefits (availability bias) and current adherence rate (social norm).
RESULTS
Caregivers in Intervention 1 had a significantly higher adherence rate than Control (97.3% versus 90.9%) (p = 0.014). Both interventions had a significant effect on participants in their first prophylaxis season (p = 0.031, p = 0.037). Families where the father was employed had a 14.2% higher adherence rate (p = 0.001). Every additional child was associated with a 2.2% decrease in adherence rate (p = 0.02). In control, ICU admission history was associated with an 18.8% lower adherence rate (p = 0.0001), but this association disappeared in intervention groups.
CONCLUSION
This is the first prospective interventional study which, in the context of palivizumab prophylaxis, analyses the effectiveness of nudge interventions based on established cognitive biases by comparing randomly generated intervention and control groups. We found that default bias and implementation intention have significant effects on adherence.Clinical trial, in the name and number "Adherence of palivizumab prophylaxis, NCT05778240" registered retrospectively. https://clinicaltrials.gov/ct2/show/NCT05778240.
PubMed: 38664919
DOI: 10.1017/S1047951124024946