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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 -
BMC Infectious Diseases Apr 2024Palivizumab has proven effective in reducing hospitalizations, preventing severe illness, improving health outcomes, and reducing healthcare costs for infants at risk of...
AIM
Palivizumab has proven effective in reducing hospitalizations, preventing severe illness, improving health outcomes, and reducing healthcare costs for infants at risk of respiratory syncytial virus (RSV) infection. We aim to assess the value of palivizumab in preventing RSV infection in high-risk infants in Colombia, where RSV poses a significant threat, causing severe respiratory illness and hospitalizations.
METHODS
We conducted a decision tree analysis to compare five doses of palivizumab with no palivizumab. The study considered three population groups: preterm neonates (≤ 35 weeks gestational age), infants with bronchopulmonary dysplasia (BPD), and infants with hemodynamically significant congenital heart disease (CHD). We obtained clinical efficacy data from IMpact-RSV and Cardiac Synagis trials, while we derived neonatal hospitalization risks from the SENTINEL-1 study. We based hospitalization and recurrent wheezing management costs on Colombian analyses and validated them by experts. We estimated incremental cost-effectiveness ratios and performed 1,000 Monte Carlo simulations for probabilistic sensitivity analyses.
RESULTS
Palivizumab is a dominant strategy for preventing RSV infection in preterm neonates and infants with BPD and CHD. Its high efficacy (78% in preventing RSV in preterm infants), the substantial risk of illness and hospitalization, and the high costs associated with hospitalization, particularly in neonatal intensive care settings, support this finding. The scatter plots and willingness-to-pay curves align with these results.
CONCLUSION
Palivizumab is a cost-saving strategy in Colombia, effectively preventing RSV infection in preterm neonates and infants with BPD and CHD by reducing hospitalizations and lowering healthcare costs.
Topics: Infant; Infant, Newborn; Humans; Palivizumab; Respiratory Syncytial Virus Infections; Cost-Benefit Analysis; Colombia; Antiviral Agents; Infant, Premature; Antibodies, Monoclonal, Humanized; Respiratory Syncytial Virus, Human; Heart Defects, Congenital; Hospitalization
PubMed: 38641577
DOI: 10.1186/s12879-024-09300-5 -
Neonatal Network : NN Apr 2024Respiratory syncytial virus (RSV) is the leading cause of hospitalization in infancy in the United States. Nearly all infants are infected by 2 years of age, with...
Respiratory syncytial virus (RSV) is the leading cause of hospitalization in infancy in the United States. Nearly all infants are infected by 2 years of age, with bronchiolitis requiring hospitalization often occurring in previously healthy children and long-term consequences of severe disease including delayed speech development and asthma. Incomplete passage of maternal immunity and a high degree of genetic variability within the virus contribute to morbidity and have also prevented successful neonatal vaccine development. Monoclonal antibodies reduce the risk of hospitalization from severe RSV disease, with palivizumab protecting high-risk newborns with comorbidities including chronic lung disease and congenital heart disease. Unfortunately, palivizumab is costly and requires monthly administration of up to five doses during the RSV season for optimal protection.Rapid advances in the past two decades have facilitated the identification of antibodies with broad neutralizing activity and allowed manipulation of their genetic code to extend half-life. These advances have culminated with nirsevimab, a monoclonal antibody targeting the Ø antigenic site on the RSV prefusion protein and protecting infants from severe disease for an entire 5-month season with a single dose. Four landmark randomized controlled trials, the first published in July 2020, have documented the efficacy and safety of nirsevimab in healthy late-preterm and term infants, healthy preterm infants, and high-risk preterm infants and those with congenital heart disease. Nirsevimab reduces the risk of RSV disease requiring medical attention (number needed to treat [NNT] 14-24) and hospitalization (NNT 33-63) with rare mild rash and injection site reactions. Consequently, the Centers for Disease Control and Prevention has recently recommended nirsevimab for all infants younger than 8 months of age entering or born during the RSV season and high-risk infants 8-19 months of age entering their second season. Implementing this novel therapy in this large population will require close multidisciplinary collaboration. Equitable distribution through minimizing barriers and maximizing uptake must be prioritized.
Topics: Humans; Infant, Newborn; Antibodies, Monoclonal, Humanized; Antiviral Agents; Heart Defects, Congenital; Infant, Premature; Palivizumab; Respiratory Syncytial Virus Infections; United States; Randomized Controlled Trials as Topic
PubMed: 38599778
DOI: 10.1891/NN-2023-0056 -
The Journal of Infection May 2024This study investigated the prevalence, genetic diversity, and evolution of human respiratory syncytial virus (HRSV) in Barcelona from 2013 to 2023.
OBJECTIVES
This study investigated the prevalence, genetic diversity, and evolution of human respiratory syncytial virus (HRSV) in Barcelona from 2013 to 2023.
METHODS
Respiratory specimens from patients with RTI suspicion at Hospital Universitari Vall d'Hebron were collected from October 2013 to May 2023 for laboratory-confirmation of respiratory viruses. Next-generation sequencing was performed in randomly-selected samples with Illumina technology. Phylogenetic analyses of whole genome sequences were performed with BEAST v1.10.4. Signals of selection and evolutionary pressures were inferred by population dynamics and evolutionary analyses. Mutations in major surface proteins were genetic and structurally characterised, emphasizing those within antigenic epitopes.
RESULTS
Analyzing 139,625 samples, 5.3% were HRSV-positive (3008 HRSV-A, 3882 HRSV-B, 56 HRSV-A and -B, and 495 unsubtyped HRSV), with a higher prevalence observed in the paediatric population. Pandemic-related shifts in seasonal patterns returned to normal in 2022-2023. A total of 198 whole-genome sequences were obtained for HRSV-A (6.6% of the HRSV-A positive samples) belonging to GA2.3.5 lineage. For HRSV-B, 167 samples were sequenced (4.3% of the HRSV-B positive samples), belonging to GB5.0.2, GB5.0.4a and GB5.0.5a. HRSV-B exhibited a higher evolution rate. Post-SARS-CoV-2 pandemic, both subtypes showed increased evolutionary rates and decreased effective population size initially, followed by a sharp increase. Analyses indicated negative selective pressure on HRSV. Mutations in antigenic epitopes, including S276N and M274I in palivizumab-targeted site II, and I206M, Q209R, and S211N in nirsevimab-targeted site Ø, were identified.
DISCUSSION
Particularly in the context of the large-scale use in 2023-2024 season of nirsevimab, continuous epidemiological and genomic surveillance is crucial.
Topics: Humans; Respiratory Syncytial Virus, Human; Respiratory Syncytial Virus Infections; Phylogeny; Child, Preschool; Child; Male; Infant; Evolution, Molecular; Female; Genome, Viral; Middle Aged; Spain; Adolescent; Adult; Genetic Variation; Antibodies, Monoclonal; Aged; Young Adult; Mutation; Whole Genome Sequencing; Antibodies, Viral; Prevalence; High-Throughput Nucleotide Sequencing; Infant, Newborn
PubMed: 38588960
DOI: 10.1016/j.jinf.2024.106153 -
Journal of the Pediatric Infectious... Apr 2024The efforts to prevent RSV infection in infants span over half a century. RSV vaccine development began in the 1960s, and it confronted a significant disappointment...
A Historical Perspective on RSV Prevention: A Journey Spanning Over Half a Century from the Setback of an Inactive Vaccine Candidate to the Success of Passive Immunization Strategy.
The efforts to prevent RSV infection in infants span over half a century. RSV vaccine development began in the 1960s, and it confronted a significant disappointment after testing a formalin inactivated RSV (FI RSV) vaccine candidate. This inactivated RSV vaccine was not protective. A large number of the vaccinated RSV naïve children, when subsequently exposed to natural RSV infection from wild type virus in the community, developed severe lung inflammation termed enhanced respiratory disease. This resulted in a halt in RSV vaccine development. In the 1990s, attention turned to the potential for passive protection against severe RSV disease with immunoglobulin administration. This led to studies on using standard intravenous immunoglobulins in high-risk infants, followed by high-titer RSV immunoglobulin preparation and, subsequently, the development of RSV monoclonal antibodies. Over the past 25 years, palivizumab has been recognized as a safe and effective monoclonal antibody as a prevention strategy for RSV in high-risk children. Its high cost and need for monthly administration, however, has hindered its use to ~2% of the birth cohort, neglecting the vast majority of newborns, including healthy full-term infants who comprise the largest portion of RSV hospitalizations and the greatest part of the burden of RSV disease. Still these efforts, helped pave the way for the present advances in RSV prevention that hold promise for mitigating severe RSV disease for all infants.
PubMed: 38577737
DOI: 10.1093/jpids/piae027 -
Nature Communications Apr 2024Currently, only Palivizumab and Nirsevimab that target the respiratory syncytical virus (RSV) fusion protein are licensed for pre-treatment of infants....
Currently, only Palivizumab and Nirsevimab that target the respiratory syncytical virus (RSV) fusion protein are licensed for pre-treatment of infants. Glycoprotein-targeting antibodies may also provide protection against RSV. In this study, we generate monoclonal antibodies from mice immunized with G proteins from RSV-A2 and RSV-B1 strains. These monoclonal antibodies recognize six unique antigenic classes (G0-G5). None of the anti-G monoclonal antibodies neutralize RSV-A2 or RSV-B1 in vitro. In mice challenged with either RSV-A2 line 19 F or RSV-B1, one day after treatment with anti-G monoclonal antibodies, all monoclonal antibodies reduce lung pathology and significantly reduce lung infectious viral titers by more than 2 logs on day 5 post-RSV challenge. RSV dissemination in the lungs was variable and correlated with lung pathology. We demonstrate new cross-protective anti-G monoclonal antibodies targeting multiple sites including conformation-dependent class G0 MAb 77D2, CCD-specific class G1 MAb 40D8, and carboxy terminus of CCD class G5 MAb 7H11, to support development of G-targeting monoclonal antibodies against RSV.
Topics: Humans; Mice; Animals; Antibodies, Monoclonal; Respiratory Syncytial Virus Infections; Antibodies, Viral; Respiratory Syncytial Virus, Human; Viral Fusion Proteins; GTP-Binding Proteins; Respiratory Syncytial Virus Vaccines; Antibodies, Neutralizing
PubMed: 38575575
DOI: 10.1038/s41467-024-47146-2 -
European Journal of Pediatrics Jun 2024We aimed to describe differences in the epidemiology, management, and outcomes existing between centers located in countries which differ by geographical location and... (Observational Study)
Observational Study
UNLABELLED
We aimed to describe differences in the epidemiology, management, and outcomes existing between centers located in countries which differ by geographical location and economic status during to post-pandemic bronchiolitis seasons. This was a prospective observational cohort study performed in two academic centers in Latin America (LA) and three in Italy. All consecutive children with a clinical diagnosis of bronchiolitis were included, following the same data collection form. Nine hundred forty-three patients have been enrolled: 275 from the two Latin American Centers (San Jose, 215; Buenos Aires, 60), and 668 from Italy (Rome, 178; Milano, 163; Bologna, 251; Catania, 76). Children in LA had more frequently comorbidities, and only rarely received palivizumab. A higher number of patients in LA had been hospitalized in a ward (64% versus 23.9%, p < 0.001) or in a PICU (16% versus 6.2%, p < 0.001), and children in LA required overall more often respiratory support, from low flow oxygen to invasive mechanical ventilation, except for CPAP which was more used in Italy. There was no significant difference in prescription rates for antibiotics, but a significantly higher number of patients treated with systemic steroids in Italy.
CONCLUSIONS
We found significant differences in the care for children with bronchiolitis in Italy and LA. Reasons behind such differences are unclear and would require further investigations to optimize and homogenize practice all over the world.
WHAT IS KNOWN
• Bronchiolitis is among the commest cause of morbidity and mortality in infants all over the world.
WHAT IS NEW
• There are significant differences on how clinicians care for bronchiolitis in different centers and continents. Differences in care can be principally due to different local practices than differences in patients severity/presentations. • Understanding these differences should be a priority to optime and standardize bronchiolitis care globally.
Topics: Humans; Italy; Prospective Studies; Infant; Male; Female; Bronchiolitis; Latin America; Infant, Newborn; Treatment Outcome; Hospitalization; Child, Preschool; Palivizumab
PubMed: 38554172
DOI: 10.1007/s00431-024-05530-6 -
Italian Journal of Pediatrics Mar 2024Respiratory Syncytial Virus (RSV) infections may lead to severe consequences in infants born preterm with breathing problems (such as bronchopulmonary dysplasia (BPD)...
BACKGROUND
Respiratory Syncytial Virus (RSV) infections may lead to severe consequences in infants born preterm with breathing problems (such as bronchopulmonary dysplasia (BPD) and respiratory distress syndrome (RDS)) or congenital heart diseases (CHD). Since studies investigating the influence of different gestational age (WGA) and concomitant specific comorbidities on the burden of RSV infections are scarce, the present study aimed to better characterize these high-risk populations in the Italian context.
METHODS
This retrospective, longitudinal and record-linkage cohort study involved infants born between 2017 and 2019 in Lazio Region (Italy) and is based on data extracted from administrative databases. Each infant was exclusively included in one of the following cohorts: (1) BPD-RDS (WGA ≤35 with or without CHD) or (2) CHD (without BPD and/or RDS) or (3) Preterm (WGA ≤35 without BPD (and/or RDS) or CHD). Each cohort was followed for 12 months from birth. Information related to sociodemographic at birth, and RSV and Undetermined Respiratory Agents (URA) hospitalizations and drug consumption at follow-up were retrieved and described.
RESULTS
A total of 8,196 infants were selected and classified as 1,084 BPD-RDS, 3,286 CHD and 3,826 Preterm. More than 30% of the BPD-RDS cohort was composed by early preterm infants (WGA ≤ 29) in contrast to the Preterm cohort predominantly constitute by moderate preterm infants (98.2%), while CHD infants were primarily born at term (83.9%). At follow-up, despite the cohorts showed similar proportions of RSV hospitalizations, in BPD-RDS cohort hospitalizations were more frequently severe compared to those occurred in the Preterm cohort (p<0.01), in the BPD-RDS cohort was also found the highest proportion of URA hospitalizations (p<0.0001). In addition, BPD-RDS infants, compared to those of the remaining cohorts, received more frequently prophylaxis with palivizumab (p<0.0001) and were more frequently treated with adrenergics inhalants, and glucocorticoids for systemic use.
CONCLUSIONS
The assessment of the study clinical outcomes highlighted that, the demographic and clinical characteristics at birth of the study cohorts influence their level of vulnerability to RSV and URA infections. As such, continuous monitoring of these populations is necessary in order to ensure a timely organization of health care system able to respond to their needs in the future.
Topics: Infant; Infant, Newborn; Humans; Respiratory Syncytial Virus Infections; Infant, Premature; Retrospective Studies; Cohort Studies; Palivizumab; Hospitalization; Heart Defects, Congenital; Bronchopulmonary Dysplasia; Antiviral Agents
PubMed: 38528568
DOI: 10.1186/s13052-024-01627-8 -
Infection & Chemotherapy Mar 2024We aimed to evaluate the clinical features of respiratory syncytial virus (RSV) infection and risk factors for severe RSV disease among Korean children in 2022/2023. A...
We aimed to evaluate the clinical features of respiratory syncytial virus (RSV) infection and risk factors for severe RSV disease among Korean children in 2022/2023. A total of 235 children were identified, and 84.3% were hospitalized. Patients under 3 months and 2 years of age accounted for 20.9% and 54.5%, respectively. Pneumonia was diagnosed in 40.9% of children and bronchiolitis in 23.8%. Respiratory support and intensive care were required in 43.4% and 7.7% of patients, respectively. nasopharyngeal colonization and the presence of underlying disease showed a significant correlation with severity indicators. The clinical impact of RSV infection was high on infants and toddlers, even those having no underlying disease or not being indicated for palivizumab.
PubMed: 38527782
DOI: 10.3947/ic.2023.0076 -
Human Vaccines & Immunotherapeutics Dec 2024Respiratory syncytial virus (RSV) is a highly contagious virus that affects the lungs and respiratory passages of many vulnerable people. It is a leading cause of lower...
Respiratory syncytial virus (RSV) is a highly contagious virus that affects the lungs and respiratory passages of many vulnerable people. It is a leading cause of lower respiratory tract infections and clinical complications, particularly among infants and elderly. It can develop into serious complications such as pneumonia and bronchiolitis. The development of RSV vaccine or immunoprophylaxis remains highly active and a global health priority. Currently, GSK's Arexvy™ vaccine is approved for the prevention of lower respiratory tract disease in older adults (>60 years). Palivizumab and currently nirsevimab are the approved monoclonal antibodies (mAbs) for RSV prevention in high-risk patients. Many studies are ongoing to develop additional therapeutic antibodies for preventing RSV infections among newborns and other susceptible groups. Recently, additional antibodies have been discovered and shown greater potential for development as therapeutic alternatives to palivizumab and nirsevimab. Plant expression platforms have proven successful in producing recombinant proteins, including antibodies, offering a potential cost-effective alternative to mammalian expression platforms. Hence in this study, an attempt was made to use a plant expression platform to produce two anti-RSV fusion (F) mAbs 5C4 and CR9501. The heavy-chain and light-chain sequences of both these antibodies were transiently expressed in plants using a geminiviral vector and then purified using single-step protein A affinity column chromatography. Both these plant-produced mAbs showed specific binding to the RSV fusion protein and demonstrate effective viral neutralization activity . These preliminary findings suggest that plant-produced anti-RSV mAbs are able to neutralize RSV .
Topics: Infant; Animals; Humans; Infant, Newborn; Aged; Palivizumab; Nicotiana; Respiratory Syncytial Virus Infections; Antibodies, Monoclonal; Antibodies, Viral; Respiratory Syncytial Virus, Human; Antibodies, Neutralizing; Viral Fusion Proteins; Respiratory Syncytial Virus Vaccines; Mammals
PubMed: 38508690
DOI: 10.1080/21645515.2024.2327142