-
Molecules (Basel, Switzerland) Jan 2024Respiratory syncytial virus (RSV) is a significant viral pathogen that causes respiratory infections in infants, the elderly, and immunocompromised individuals.... (Review)
Review
Respiratory syncytial virus (RSV) is a significant viral pathogen that causes respiratory infections in infants, the elderly, and immunocompromised individuals. RSV-related illnesses impose a substantial economic burden worldwide annually. The molecular structure, function, and in vivo interaction mechanisms of RSV have received more comprehensive attention in recent times, and significant progress has been made in developing inhibitors targeting various stages of the RSV replication cycle. These include fusion inhibitors, RSV polymerase inhibitors, and nucleoprotein inhibitors, as well as FDA-approved RSV prophylactic drugs palivizumab and nirsevimab. The research community is hopeful that these developments might provide easier access to knowledge and might spark new ideas for research programs.
Topics: Humans; Infant; Aged; Antiviral Agents; Palivizumab; Respiratory Syncytial Virus, Human; Respiratory Syncytial Virus Infections; Anti-Retroviral Agents
PubMed: 38338343
DOI: 10.3390/molecules29030598 -
Expert Review of Respiratory Medicine Jan 2018Palivizumab is a humanized monoclonal antibody used for respiratory syncytial virus (RSV) prophylaxis. RSV is the primary cause of lower respiratory tract infection in... (Review)
Review
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.
Topics: Antiviral Agents; Cost-Benefit Analysis; Humans; Infant; Infant, Newborn; Palivizumab; Respiratory Syncytial Virus Infections; Treatment Outcome
PubMed: 29130355
DOI: 10.1080/17476348.2018.1401926 -
Pediatrics Jul 2023Guidance from the American Academy of Pediatrics (AAP) for the use of palivizumab prophylaxis against respiratory syncytial virus (RSV) was first published in a policy...
Guidance from the American Academy of Pediatrics (AAP) for the use of palivizumab prophylaxis against respiratory syncytial virus (RSV) was first published in a policy statement in 1998. AAP recommendations have been updated periodically to reflect the most recent literature regarding children at greatest risk of severe RSV disease. Since the last update in 2014, which refined prophylaxis guidance to focus on those children at greatest risk, data have become available regarding the seasonality of RSV circulation, the incidence and risk factors associated with bronchiolitis hospitalizations, and the potential effects of the implementation of prophylaxis recommendations on hospitalization rates of children with RSV infection. This technical report summarizes the literature review by the Committee on Infectious Diseases, supporting the reaffirmation of the 2014 AAP policy statement on palivizumab prophylaxis among infants and young children at increased risk of hospitalization for RSV infection. Review of publications since 2014 did not support a change in recommendations for palivizumab prophylaxis and continues to endorse the guidance provided in the 2021 Red Book.
Topics: Infant; Child; Humans; Child, Preschool; Palivizumab; Respiratory Syncytial Virus Infections; Antiviral Agents; Antibodies, Monoclonal, Humanized; Respiratory Syncytial Viruses; Hospitalization
PubMed: 37357729
DOI: 10.1542/peds.2023-061803 -
Journal of Paediatrics and Child Health Dec 2018Palivizumab prevents respiratory syncytial virus (RSV) in children at high risk of severe disease. This paper reviews the use and effectiveness of palivizumab at two...
AIM
Palivizumab prevents respiratory syncytial virus (RSV) in children at high risk of severe disease. This paper reviews the use and effectiveness of palivizumab at two tertiary paediatric hospitals (hospitals A and B) in New South Wales, Australia.
METHODS
Children prescribed palivizumab during the pre-intervention period, 1 January 2013 until 31 December 2014, were compared with children under 2 years of age who were admitted to paediatric intensive care units (PICUs) with an RSV infection. Eligibility for palivizumab was determined. To improve evidence-based utilisation of palivizumab, a 'streamlined palivizumab individual patient use' (IPU) pro forma was introduced at hospital A during 2015, and its applicability was reviewed.
RESULTS
In the 2 years prior to implementing the streamlined IPU, 47 children received palivizumab, with 87% at hospital A. Of the children at hospital A, 32% did not meet the guidelines, and 32% did not complete the course. While 13% of children admitted to PICU for RSV infection were eligible for palivizumab, none received it prior to admission. In 2015, 16 streamlined IPUs were submitted, and 11 patients received palivizumab. Of these patients, 27% did not meet the guidelines, and 63% did not complete the course. Of the children who received palivizumab during the three RSV seasons, one developed an RSV infection, and none were admitted to PICU.
CONCLUSIONS
Palivizumab is often prescribed without meeting recognised best practice guidelines, and patients eligible are frequently not prescribed palivizumab. The streamlined IPU, implemented in hospital A, excluded patients who did not meet guidelines. The pro forma needs further refinement, and complementary strategies introduced to improve compliance.
Topics: Antiviral Agents; Drug Prescriptions; Humans; Intensive Care Units, Pediatric; Neonatology; New South Wales; Palivizumab; Pediatrics; Quality Improvement; Respiratory Syncytial Virus Infections; Treatment Outcome
PubMed: 29863814
DOI: 10.1111/jpc.14083 -
Reviews in Medical Virology May 2022Respiratory syncytial virus (RSV) is a major health problem. A better understanding of the geographical and temporal dynamics of RSV circulation will assist in tracking... (Review)
Review
Respiratory syncytial virus (RSV) is a major health problem. A better understanding of the geographical and temporal dynamics of RSV circulation will assist in tracking resistance against therapeutics currently under development. Since 2015, the field of RSV molecular epidemiology has evolved rapidly with around 20-30 published articles per year. The objective of this systematic review is to identify knowledge gaps in recent RSV genetic literature to guide global molecular epidemiology research. We included 78 studies published between 2015 and 2020 describing 12,998 RSV sequences of which 8,233 (63%) have been uploaded to GenBank. Seventeen (22%) studies were performed in low- and middle-income countries (LMICs), and seven (9%) studies sequenced whole-genomes. Although most reported polymorphisms for monoclonal antibodies in clinical development (nirsevimab, MK-1654) have not been tested for resistance in neutralisation essays, known resistance was detected at low levels for the nirsevimab and palivizumab binding site. High resistance was found for the suptavumab binding site. We present the first literature review of an enormous amount of RSV genetic data. The need for global monitoring of RSV molecular epidemiology becomes increasingly important in evaluating the effectiveness of monoclonal antibody candidates as they reach their final stages of clinical development. We have identified the following three knowledge gaps: whole-genome data to study global RSV evolution, data from LMICs and data from global surveillance programs.
Topics: Antibodies, Monoclonal; Antiviral Agents; Humans; Palivizumab; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human
PubMed: 34543489
DOI: 10.1002/rmv.2284 -
Journal of Proteins and Proteomics 2022Viral infections are progressively becoming a global health burden, as witnessed in the ongoing COVID-19 pandemic. Respiratory Syncytial Virus (RSV) is another highly...
UNLABELLED
Viral infections are progressively becoming a global health burden, as witnessed in the ongoing COVID-19 pandemic. Respiratory Syncytial Virus (RSV) is another highly contagious negative-sense RNA virus that causes lower respiratory tract infections and high mortality in infants. Palivizumab (Synagis) is the only humanized monoclonal antibody (mAb) approved by the FDA against RSV. The virus neutralization efficacy often depends on the nature and abundance of the glycoforms in therapeutic mAbs. Therefore, a thorough estimation of their PTM profile, especially glycosylation, is relevant. Here, we describe the intact and released glycan analysis of palivizumab (Synagis) using HILIC chromatography and mass spectrometry. We detected five glycoforms (Man5/G0FB, G0F/G1F, G1F/G1F, G0FB/G0FB, and G2F/G2F) in deconvoluted MS spectra of intact glycosylated palivizumab. The mapping of the peptide and glycopeptides using LC-ESI-MS led to the detection of associated PTMs and the direct identification of a glycopeptide, GlcNAcMan. EEQYNSTYR, derived from the heavy chain of palivizumab.Release glycan analysis using UHPLC-HILIC revealed a typical glycan profile consisting of major glycans, G0F (33.94%), G1F (35.50%), G2F (17.24%) also reported previously and minor G1F' (5.81%), Man5 (3.96%) and G0FB (2.26%) forms with the superior resolution of isomeric G1F/G1F'. Next, we provide the first experimental evidence of Neu5Gc in the commercial palivizumab formulation using DMB labelling. The estimated monosaccharide composition was consistent with previous studies. The findings of the study highlight the efficiency of the release glycan method in providing a correct measure of the total palivizumab glycan pool compared to the intact glycoprotein/glycopeptide approach. The UHPLC-RPLC/HILIC and MS combinations provide a more comprehensive glycoprofile assessment due to the parallel use of fluorescent labels for the analysis of the release of -glycan, sialic acid, and monosaccharide composition. This approach is suitable for quick quality testing and market surveillance of therapeutic mAbs. Alongside a well-perceived need for cost-effective immunoprophylaxis and the ongoing fast-paced development of next-generation variants of palivizumab, such as MEDI8897, the study reiterates glycosylation as a critical parameter that needs monitoring for drug characterization and quality control.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s42485-022-00086-1.
PubMed: 35572846
DOI: 10.1007/s42485-022-00086-1 -
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 -
British Journal of Hospital Medicine... May 2019Bronchiolitis is an acute respiratory illness that is the leading cause of hospitalization in young children less than 2 years of age in the UK. Respiratory syncytial... (Review)
Review
Bronchiolitis is an acute respiratory illness that is the leading cause of hospitalization in young children less than 2 years of age in the UK. Respiratory syncytial virus is the most common virus associated with bronchiolitis and has the highest disease severity, mortality and cost. Bronchiolitis is generally a self-limiting condition, but can have serious consequences in infants who are very young, premature, or have underlying comorbidities. Management of bronchiolitis in the UK is guided by the National Institute for Health and Care Excellence (2015) guidance. The mainstays of management are largely supportive, consisting of fluid management and respiratory support. Pharmacological interventions including nebulized bronchodilators, steroids and antibiotics generally have limited or no evidence of efficacy and are not advised by National Institute of Health and Care Excellence. Antiviral therapeutics remain in development. As treatments are limited, there have been extensive efforts to develop vaccines, mainly targeting respiratory syncytial virus. At present, the only licensed product is a monoclonal antibody for passive immunisation. Its cost restricts its use to those at highest risk. Vaccines for active immunisation of pregnant women and young infants are also being developed.
Topics: Bronchiolitis; Bronchodilator Agents; Cannula; Clinical Protocols; Fluid Therapy; Glucocorticoids; Humans; Oxygen Inhalation Therapy; Palivizumab; Respiratory Syncytial Virus Infections; State Medicine; United Kingdom
PubMed: 31059347
DOI: 10.12968/hmed.2019.80.5.278 -
Future Cardiology Sep 2018Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infections and causes up to 200,000 infant deaths a year worldwide. The average... (Review)
Review
Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infections and causes up to 200,000 infant deaths a year worldwide. The average rate of hospitalization for severe RSV infection is 5 per 1000 children, and the rate is three-times higher in those with congenital heart disease (CHD). Palivizumab, a monoclonal antibody, reduces hospitalization rates and intensive care admissions. It is used prophylactically and is administered as monthly doses during the RSV season. Hemodynamically unstable CHD is the most susceptible CHD to a severe episode of RSV infection. This review explores current evidence surrounding therapies, patterns of infection and identifies groups which may still be vulnerable to severe RSV infection.
Topics: Antibodies, Monoclonal, Humanized; Cost-Benefit Analysis; Disease Susceptibility; Female; Heart Defects, Congenital; Hospitalization; Humans; Infant, Newborn; Male; Palivizumab; Practice Guidelines as Topic; Primary Prevention; Prognosis; Respiratory Syncytial Virus Infections; Treatment Outcome
PubMed: 29877720
DOI: 10.2217/fca-2017-0096 -
Drug, Healthcare and Patient Safety 2023Respiratory Syncytial Virus (RSV) is a major global cause of childhood morbidity and mortality. Palivizumab, a monoclonal antibody that provides passive immunity against... (Review)
Review
Respiratory Syncytial Virus (RSV) is a major global cause of childhood morbidity and mortality. Palivizumab, a monoclonal antibody that provides passive immunity against RSV, is currently licensed for prophylactic use in specific "high-risk" populations, including congenital heart disease, bronchopulmonary dysplasia and prematurity. Available research suggests palivizumab use in these high-risk populations can lead to a reduction in RSV-related hospitalization. However, palivizumab has not been demonstrated to reduce mortality, adverse events or length of hospital stay related to RSV. In this article, we review the management of RSV, indications for palivizumab prophylaxis, the safety, cost-effectiveness and efficacy of this preventative medication, and emerging therapeutics that could revolutionize future prevention of this significant pathogen.
PubMed: 37720805
DOI: 10.2147/DHPS.S348727