scholarly journals Passive Immunoprophylaxis against Respiratory Syncytial Virus in Children: Where Are We Now?

2021 ◽  
Vol 22 (7) ◽  
pp. 3703
Author(s):  
Alessandro Rocca ◽  
Carlotta Biagi ◽  
Sara Scarpini ◽  
Arianna Dondi ◽  
Silvia Vandini ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Neuromuscular Disorders ◽  
Passive Immunization ◽  
Symptomatic Treatment ◽  
Effective Vaccine ◽  
Radiographic Appearance ◽  
Development Of Resistance ◽  
Increased Risk ◽  
Syncytial Virus ◽  
Tract Infections

Respiratory syncytial virus (RSV) represents the main cause of acute respiratory tract infections in children worldwide and is the leading cause of hospitalization in infants. RSV infection is a self-limiting condition and does not require antibiotics. However hospitalized infants with clinical bronchiolitis often receive antibiotics for fear of bacteria coinfection, especially when chest radiography is performed due to similar radiographic appearance of infiltrate and atelectasis. This may lead to unnecessary antibiotic prescription, additional cost, and increased risk of development of resistance. Despite the considerable burden of RSV bronchiolitis, to date, only symptomatic treatment is available, and there are no commercially available vaccines. The only licensed passive immunoprophylaxis is palivizumab. The high cost of this monoclonal antibody (mAb) has led to limiting its prescription only for high-risk children: infants with chronic lung disease, congenital heart disease, neuromuscular disorders, immunodeficiencies, and extreme preterm birth. Nevertheless, it has been shown that the majority of hospitalized RSV-infected children do not fully meet the criteria for immune prophylaxis. While waiting for an effective vaccine, passive immune prophylaxis in children is mandatory. There are a growing number of RSV passive immunization candidates under development intended for RSV prevention in all infants. In this review, we describe the state-of-the-art of palivizumab’s usage and summarize the clinical and preclinical trials regarding the development of mAbs with a better cost-effectiveness ratio.

scholarly journals Current State and Challenges in Developing Respiratory Syncytial Virus Vaccines

Vaccines ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 672
Author(s):  
Carlotta Biagi ◽  
Arianna Dondi ◽  
Sara Scarpini ◽  
Alessandro Rocca ◽  
Silvia Vandini ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
High Risk ◽  
Clinical Stage ◽  
Passive Immunization ◽  
The Elderly ◽  
Effective Vaccine ◽  
Stage Of Development ◽  
High Risk Populations ◽  
Syncytial Virus ◽  
Tract Infections

Respiratory syncytial virus (RSV) is the main cause of acute respiratory tract infections in infants and it also induces significant disease in the elderly. The clinical course may be severe, especially in high-risk populations (infants and elderly), with a large number of deaths in developing countries and of intensive care hospitalizations worldwide. To date, prevention strategies against RSV infection is based on hygienic measures and passive immunization with humanized monoclonal antibodies, limited to selected high-risk children due to their high costs. The development of a safe and effective vaccine is a global health need and an important objective of research in this field. A growing number of RSV vaccine candidates in different formats (particle-based vaccines, vector-based vaccines, subunit vaccines and live-attenuated vaccines) are being developed and are now at different stages, many of them already being in the clinical stage. While waiting for commercially available safe and effective vaccines, immune prophylaxis in selected groups of high-risk populations is still mandatory. This review summarizes the state-of-the-art of the RSV vaccine research and its implications for clinical practice, focusing on the characteristics of the vaccines that reached the clinical stage of development.

scholarly journals Clinical burden of severe respiratory syncytial virus infection during the first 2 years of life in children born between 2000 and 2011 in Scotland

2020 ◽  
Vol 179 (5) ◽  
pp. 791-799 ◽  
Author(s):  
Richard Thwaites ◽  
Scot Buchan ◽  
John Fullarton ◽  
Carole Morris ◽  
ElizaBeth Grubb ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Neuromuscular Disorders ◽  
International Classification Of Diseases ◽  
National Data ◽  
Clinical Burden ◽  
Increased Risk ◽  
Classification Of Diseases ◽  
Bed Days ◽  
Syncytial Virus

AbstractNational data from Scotland (all births from 2000 to 2011) were used to estimate the burden associated with respiratory syncytial virus hospitalisation (RSVH) during the first 2 years of life. RSVHs were identified using the International Classification of Diseases 10th Revision codes. Of 623,770 children, 13,362 (2.1%) had ≥ 1 RSVH by 2 years, with the overall rate being 27.2/1000 (16,946 total RSVHs). Median age at first RSVH was 137 days (interquartile range [IQR] 62–264), with 84.3% of admissions occurring by 1 year. Median length of stay was 2 (IQR 1–4) days and intensive care unit (ICU) admission was required by 4.3% (727) for a median 5 (IQR 2–8) days. RSVHs accounted for 6.9% (5089/73,525) of ICU bed days and 6.2% (64,395/1,033,121) of overall bed days (5370/year). RSVHs represented 8.5% (14,243/168,205) of all admissions between October and March and 14.2% (8470/59,535) between December and January. RSVH incidence ranged from 1.7 to 2.5%/year over the study period. Preterms (RSVH incidence 5.2%), and those with congenital heart disease (10.5%), congenital lung disease (11.2%), Down syndrome (14.8%), cerebral palsy (15.5%), cystic fibrosis (12.6%), and neuromuscular disorders (17.0%) were at increased risk of RSVH.Conclusions: RSV causes a substantial burden on Scottish paediatric services during the winter months.What is known:• Respiratory syncytial virus (RSV) is a leading cause of childhood hospitalisation.What is new:• This 12-year study is the first to estimate the burden of RSV hospitalisation (RSVH) in Scotland and included all live births from 2000 to 2011 and followed > 600,000 children until 2 years old.• The overall RSVH rate was 27.2/1000 children, with 2.1% being hospitalised ≥ 1 times.• RSVHs accounted for 6.2% of all inpatient bed days, which rose to 14.2% during the peak months of the RSV season (December–January), equating to over 1400 hospitalisations and nearly 5500 bed days each year.

scholarly journals Respiratory Syncytial Virus Prophylaxis in Infants With Congenital Diaphragmatic Hernia in the Canadian Respiratory Syncytial Virus Evaluation Study of Palivizumab, 2005–2017

2018 ◽  
Vol 69 (6) ◽  
pp. 980-986 ◽  
Author(s):  
Doyoung Kim ◽  
Mahwesh Saleem ◽  
Bosco Paes ◽  
Ian Mitchell ◽  
Krista L Lanctôt
Keyword(s):  
Respiratory Syncytial Virus ◽  
Congenital Diaphragmatic Hernia ◽  
Diaphragmatic Hernia ◽  
Respiratory Illness ◽  
Evaluation Study ◽  
Cox Proportional Hazards ◽  
Respiratory Morbidity ◽  
Increased Risk ◽  
Syncytial Virus ◽  
Tract Infections

Abstract 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.

scholarly journals RSV604, a Novel Inhibitor of Respiratory Syncytial Virus Replication

2007 ◽  
Vol 51 (9) ◽  
pp. 3346-3353 ◽  
Author(s):  
Joanna Chapman ◽  
Elizabeth Abbott ◽  
Dagmar G. Alber ◽  
Robert C. Baxter ◽  
Sian K. Bithell ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Virus Replication ◽  
Cell Model ◽  
Antiviral Treatment ◽  
Effective Vaccine ◽  
Initial Development ◽  
Basolateral Side ◽  
Syncytial Virus ◽  
Tract Infections

ABSTRACT Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infections worldwide, yet no effective vaccine or antiviral treatment is available. Here we report the discovery and initial development of RSV604, a novel benzodiazepine with submicromolar anti-RSV activity. It proved to be equipotent against all clinical isolates tested of both the A and B subtypes of the virus. The compound has a low rate of in vitro resistance development. Sequencing revealed that the resistant virus had mutations within the nucleocapsid protein. This is a novel mechanism of action for anti-RSV compounds. In a three-dimensional human airway epithelial cell model, RSV604 was able to pass from the basolateral side of the epithelium effectively to inhibit virus replication after mucosal inoculation. RSV604, which is currently in phase II clinical trials, represents the first in a new class of RSV inhibitors and may have significant potential for the effective treatment of RSV disease.

scholarly journals Effect of monoclonal antibodies to respiratory syncytial virus in preterm children with bronchopulmonary dysplasia according to follow-up

2015 ◽  
Vol 96 (4) ◽  
pp. 505-509
Author(s):  
E V Volyanyuk ◽  
A I Safina ◽  
M V Potapova
Keyword(s):  
Respiratory Syncytial Virus ◽  
Bronchopulmonary Dysplasia ◽  
Respiratory Infections ◽  
Passive Immunization ◽  
Postnatal Life ◽  
Preterm Children ◽  
Very Preterm Infants ◽  
Syncytial Virus ◽  
Tract Infections

Aim. To assess the effect and safety of palivizumab to prevent the bronchopulmonary dysplasia complications in preterm children according to follow-up. Methods. The study included 48 very preterm infants (birth weight ranged from 732-1640 g) with bronchopulmonary dysplasia, who were divided into two groups. The main group included children who received passive immunization by palivizumab (31 children), the comparison group included un-immunized children (17 patients). The diagnosis of bronchopulmonary dysplasia in children at 28 days of postnatal life has been set according to clinical and radiological data. After being discharged from the department of pathology of newborn, children were followed-up for 12 months in the center of preterm children follow-up. Average age of patients with bronchopulmonary dysplasia was 4.2±1.3 months at passive immunization initiation. The drug was administered by intramuscular injection at a dose of 15 mg/kg once monthly. Results. Lower respiratory tract infections were observed in 6 (19.3%) patients from the first group, including 4 cases of obstructive bronchitis and 2 cases of pneumonia. These patients received incomplete course of immunization. In children who did not receive specific prophylaxis, respiratory infections were registered in 7 (41.2%) patients, with 2 cases accompanied by severe respiratory failure requiring mechanical ventilation. No adverse effects were identified while palivizumab treatment. Conclusion. Palivizumab is currently the only effective drug to prevent the severe respiratory syncytial virus infection; good safety of the drug makes it possible to reconsider the contraindication of its use in high-risk children with severe bronchopulmonary dysplasia.

scholarly journals Using linked routinely collected health data to explore the burden of respiratory syncytial virus (RSV) in Scotland

2018 ◽  
Vol 3 (4) ◽  
Author(s):  
Rachel Reeves ◽  
Anne Douglas ◽  
Harry Campbell
Keyword(s):  
Respiratory Syncytial Virus ◽  
Economic Burden ◽  
Hospital Admissions ◽  
Health Data ◽  
Icu Admission ◽  
Routinely Collected Health Data ◽  
Increased Risk ◽  
Syncytial Virus ◽  
Tract Infections ◽  
Regulatory Decisions

IntroductionRespiratory syncytial virus (RSV) is the most frequent cause of lower respiratory tract infections (RTIs), particularly bronchiolitis, in young children worldwide. In order to inform policymaking and regulatory decisions regarding novel RSV vaccines and therapeutics, the health and economic burden of RSV needs to be quantified in further detail. Objectives and ApproachThis project is part of the REspiratory Syncytial virus Consortium in Europe (RESCEU), a collaborative IMI funded EU project assembling routinely collected health data from at least seven European countries to produce detailed estimates of RSV health and economic burden. This study links national data on hospital admissions, deaths, RSV laboratory testing, prescriptions, and maternal/perinatal data. Using this linked data we calculate rates of hospital admissions, intensive care unit (ICU) admissions, and deaths (a) potentially due to RSV, (b) likely due to RSV, and (c) confirmed due to RSV. We also investigate maternal and perinatal characteristics associated with RSV-related episodes. ResultsRSV is a major cause of hospital admission in Scotland, particularly in children <6 months old. Around 2,000 admissions with a primary diagnosis of bronchiolitis occur in children <12 months old per year, on average, with approximately 75% of these estimated to be due to RSV.  Children with known clinical risk factors, such as prematurity or chronic conditions, are at increased risk of ICU admission and death due to RSV.  Results will be presented on the age- and risk-group specific hospitalisation, ICU admission and mortality rates for RSV-associated RTI in children <5 years old.  The maternal and perinatal characteristics (e.g. maternal smoking, type of delivery, breastfeeding status, birthweight, APGAR score (5 mins), mechanical ventilation, oxygen use) associated with RSV-related RTI hospital episodes will be presented. Conclusion/ImplicationsThis is the first study to explore the national burden of RSV in Scotland. Our results demonstrate the benefits of using linked routinely collected data to explore the epidemiology and burden of infectious diseases and inform policymaking and regulatory decisions. Our methodology can be applied to other countries and pathogens.

scholarly journals Palivizumab Prophylaxis among Infants at Increased Risk of Hospitalization due to Respiratory Syncytial Virus Infection in UAE: A Hospital-Based Study

2019 ◽  
Vol 2019 ◽  
pp. 1-8
Author(s):  
M. Elhalik ◽  
K. El-Atawi ◽  
S.K. Dash ◽  
A. Faquih ◽  
A.D. Satyan ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
High Risk ◽  
Compliance Rate ◽  
Public Health Burden ◽  
Increased Risk ◽  
Significant Public Health ◽  
High Compliance Rate ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Tract Infections

Background. Respiratory syncytial virus (RSV) represents a significant public health burden and the leading cause of lower respiratory tract infections globally, and it is the major cause of hospitalization during the winter. We aimed to evaluate the effectiveness of palivizumab prophylaxis to reduce the hospitalization in children at high risk of RSV infection. Methods. We performed a retrospective observational single-arm hospital-based study including five RSV seasons (September to March) from 2012 to 2017. We retrospectively included premature infants born at less than 35 weeks of gestation with chronic lungs disease or hemodynamic significant congenital heart disease for palivizumab prophylaxis against RSV infection according to the criteria presented. Results. A total of 925 children were enrolled in the study over the five RSV seasons. Of them, 410 (44.3%) infants born at <32 weeks of gestation and 515 (55.6%) infants born at 32–35 weeks of gestation with mean (±SD) birth weight of 1104.8 ± 402.85 and 1842.5 ± 377.5, respectively. The compliance with the course of palivizumab was reported in 841 (90.9%) children. Of them, about 75 (8.9%) hospitalized children were reported, and 17 (2.02%) RSV positive children were detected. Hospitalization due to RSV infection was decreased from 9.23% in the 2012-2013 season to 0.67% in the 2016-2017 season. Conclusion. This study demonstrated that palivizumab prophylaxis in children at high risk of developing RSV infection was effective in reducing the risk of hospitalization with a high compliance rate over the five RSV seasons.

scholarly journals Extracellular amoebal-vesicles: potential transmission vehicles for respiratory viruses

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Rafik Dey ◽  
Melanie A. Folkins ◽  
Nicholas J. Ashbolt
Keyword(s):  
Respiratory Syncytial Virus ◽  
Respiratory Tract ◽  
Respiratory Tract Infections ◽  
Respiratory Viruses ◽  
Environmental Persistence ◽  
Viral Dissemination ◽  
Acute Respiratory Tract Infections ◽  
High Concentrations ◽  
Syncytial Virus ◽  
Tract Infections

AbstractHuman respiratory syncytial virus (RSV) is a major cause of acute respiratory tract infections in children and immunocompromised adults worldwide. Here we report that amoebae-release respirable-sized vesicles containing high concentrations of infectious RSV that persisted for the duration of the experiment. Given the ubiquity of amoebae in moist environments, our results suggest that extracellular amoebal-vesicles could contribute to the environmental persistence of respiratory viruses, including potential resistance to disinfection processes and thereby offering novel pathways for viral dissemination and transmission.

scholarly journals Considerations for a Respiratory Syncytial Virus Vaccine Targeting an Elderly Population

Vaccines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 624
Author(s):  
Laura M. Stephens ◽  
Steven M. Varga
Keyword(s):  
Respiratory Syncytial Virus ◽  
Disease Burden ◽  
Elderly Population ◽  
Vaccine Development ◽  
The Elderly ◽  
The United States ◽  
Susceptible Population ◽  
Age Related ◽  
Syncytial Virus ◽  
Tract Infections

Respiratory syncytial virus (RSV) is most commonly associated with acute lower respiratory tract infections in infants and children. However, RSV also causes a high disease burden in the elderly that is often under recognized. Adults >65 years of age account for an estimated 80,000 RSV-associated hospitalizations and 14,000 deaths in the United States annually. RSV infection in aged individuals can result in more severe disease symptoms including pneumonia and bronchiolitis. Given the large disease burden caused by RSV in the aged, this population remains an important target for vaccine development. Aging results in lowered immune responsiveness characterized by impairments in both innate and adaptive immunity. This immune senescence poses a challenge when developing a vaccine targeting elderly individuals. An RSV vaccine tailored towards an elderly population will need to maximize the immune response elicited in order to overcome age-related defects in the immune system. In this article, we review the hurdles that must be overcome to successfully develop an RSV vaccine for use in the elderly, and discuss the vaccine candidates currently being tested in this highly susceptible population.

scholarly journals Bacterial and Viral Coinfections with the Human Respiratory Syncytial Virus

2021 ◽  
Vol 9 (6) ◽  
pp. 1293
Author(s):  
Gaspar A. Pacheco ◽  
Nicolás M. S. Gálvez ◽  
Jorge A. Soto ◽  
Catalina A. Andrade ◽  
Alexis M. Kalergis
Keyword(s):  
Respiratory Syncytial Virus ◽  
Influenza A ◽  
Human Respiratory Syncytial Virus ◽  
Respiratory Pathogens ◽  
Parainfluenza Viruses ◽  
Starting Point ◽  
The Social ◽  
Syncytial Virus ◽  
Tract Infections ◽  
Polymicrobial Infections

The human respiratory syncytial virus (hRSV) is one of the leading causes of acute lower respiratory tract infections in children under five years old. Notably, hRSV infections can give way to pneumonia and predispose to other respiratory complications later in life, such as asthma. Even though the social and economic burden associated with hRSV infections is tremendous, there are no approved vaccines to date to prevent the disease caused by this pathogen. Recently, coinfections and superinfections have turned into an active field of study, and interactions between many viral and bacterial pathogens have been studied. hRSV is not an exception since polymicrobial infections involving this virus are common, especially when illness has evolved into pneumonia. Here, we review the epidemiology and recent findings regarding the main polymicrobial infections involving hRSV and several prevalent bacterial and viral respiratory pathogens, such as Staphylococcus aureus, Pseudomonas aeruginosa, Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Klebsiella pneumoniae, human rhinoviruses, influenza A virus, human metapneumovirus, and human parainfluenza viruses. As reports of most polymicrobial infections involving hRSV lack a molecular basis explaining the interaction between hRSV and these pathogens, we believe this review article can serve as a starting point to interesting and very much needed research in this area.

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