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CMAJ : Canadian Medical Association... Apr 2021
Topics: Antiviral Agents; COVID-19; Canada; Humans; Infant; Palivizumab; Pandemics; Practice Guidelines as Topic; Respiratory Syncytial Virus Infections; SARS-CoV-2
PubMed: 33846202
DOI: 10.1503/cmaj.78240 -
Antiviral Chemistry & Chemotherapy Nov 2002Respiratory syncytial virus (RSV) continues as an emerging infectious disease not only among infants and children, but also for the immune-suppressed, hospitalized and... (Review)
Review
Respiratory syncytial virus (RSV) continues as an emerging infectious disease not only among infants and children, but also for the immune-suppressed, hospitalized and the elderly. To date, ribavirin (Virazole) remains the only therapeutic agent approved for the treatment of RSV. The prophylactic administration of palivizumab is problematic and costly. The quest for an efficacious RSV antiviral has produced a greater understanding of the viral fusion process, a new hypothesis for the mechanism of action of ribavirin, and a promising antisense strategy combining the 2'-5' oligoadenylate antisense (2-5A-antisense) approach and RSV genomics.
Topics: 2',5'-Oligoadenylate Synthetase; Adenine Nucleotides; Adult; Aged; Animals; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antiviral Agents; Child; Child, Preschool; Drug Design; Endoribonucleases; Humans; Infant; Interferons; Membrane Fusion; Mice; Middle Aged; Molecular Structure; Oligodeoxyribonucleotides, Antisense; Oligoribonucleotides; Palivizumab; RNA, Viral; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; Ribavirin; Viral Proteins
PubMed: 12718405
DOI: 10.1177/095632020201300601 -
Children (Basel, Switzerland) Jan 2023Among prematurely born infants and newborns with chronic conditions, a respiratory syncytial virus (RSV) infection may cause (re-)admission and later respiratory...
Among prematurely born infants and newborns with chronic conditions, a respiratory syncytial virus (RSV) infection may cause (re-)admission and later respiratory complications. Therapeutic protection is possible with monthly injections of a specific monoclonal antibody, palivizumab, during RSV season. Standard care is giving up to five injections in clinic-based settings. Immunization at home could be an alternative to standard care for vulnerable infants to reduce the number of revisits and associated risk of RSV infection. The aim of this randomized pilot trial was to evaluate safety aspects and explore parents' preferences of home versus hospital immunization with palivizumab during one RSV season. Immediate adverse events (AEs) were observed and registered by a pediatric specialist nurse. Late-onset AEs were reported by parents. Parents' perceptions were collected through a questionnaire and analyzed using content analysis. The study population consisted of 43 infants in 38 families. No immediate AEs occurred. Three late-onset AEs were reported in two infants in the intervention group. Three categories emerged in the content analysis: (1) protect and watch over the infant, (2) optimal health and well-being for the whole family, and (3) avoid suffering for the infant. The study results show that home immunization with palivizumab is feasible if safety aspects are considered and that parental involvement in the choice of place for immunization after a neonatal intensive care experience can be important.
PubMed: 36832327
DOI: 10.3390/children10020198 -
Italian Journal of Pediatrics Dec 2015Respiratory Syncytial Virus infections are one of the leading causes of severe respiratory diseases that require hospitalization and, in some cases, intensive care. Once... (Review)
Review
Respiratory Syncytial Virus infections are one of the leading causes of severe respiratory diseases that require hospitalization and, in some cases, intensive care. Once resolved, there may be respiratory sequelae of varying severity. The lack of effective treatments for bronchiolitis and the lack of vaccines for RSV accentuate the role of prevention in decreasing the impact of this disease. Prevention of bronchiolitis strongly relies on the adoption of environment and the hygienic behavior measures; an additional prophylactic effect may be offered, in selected cases, by Palivizumab, a humanized monoclonal antibody produced by recombinant DNA technology, able to prevent RSV infection by blocking viral replication.After many years the Italian Society of Neonatology, on the basis of the most recent scientific knowledge, has decided to revise recommendations for the use of palivizumab in the prevention of RSV infection.
Topics: Antiviral Agents; DNA, Viral; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Palivizumab; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses
PubMed: 26670908
DOI: 10.1186/s13052-015-0203-x -
MAbs Apr 2018Respiratory syncytial virus (RSV) infection is a leading cause of hospitalization and mortality in young children. Protective therapy options are limited. Currently,...
Respiratory syncytial virus (RSV) infection is a leading cause of hospitalization and mortality in young children. Protective therapy options are limited. Currently, palivizumab, a monoclonal IgG1 antibody, is the only licensed drug for RSV prophylaxis, although other IgG antibody candidates are being evaluated. However, at the respiratory mucosa, IgA antibodies are most abundant and act as the first line of defense against invading pathogens. Therefore, it would be logical to explore the potential of recombinant human IgA antibodies to protect against viral respiratory infection, but very little research on the topic has been published. Moreover, it is unknown whether human antibodies of the IgA isotype are better suited than those of the IgG isotype as antiviral drugs to combat respiratory infections. To address this, we generated various human IgA antibody formats of palivizumab and motavizumab, two well-characterized human IgG1 anti-RSV antibodies. We evaluated their efficacy to prevent RSV infection in vitro and in vivo and found similar, but somewhat decreased efficacy for different IgA subclasses and formats. Thus, reformatting palivizumab or motavizumab into IgA reduces the antiviral potency of either antibody. Moreover, our results indicate that the efficacy of intranasal IgA prophylaxis against RSV infection in human FcαRI transgenic mice is independent of Fc receptor expression.
Topics: Animals; Antibodies, Monoclonal, Humanized; Antibodies, Viral; Cell Line; Humans; Immunoglobulin A; Immunoglobulin G; Mice; Mice, Inbred BALB C; Mice, Transgenic; Palivizumab; Protein Engineering; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses
PubMed: 29553863
DOI: 10.1080/19420862.2018.1433974 -
Respiratory Care Mar 2003Respiratory syncytial virus, the leading cause of serious upper and lower respiratory tract infection in infants and children, accounts for 125,000 hospitalizations and... (Review)
Review
Respiratory syncytial virus, the leading cause of serious upper and lower respiratory tract infection in infants and children, accounts for 125,000 hospitalizations and 450 deaths annually in the United States. It also may predispose to development of asthma later in life. Annual epidemics occur from November to April, and virtually all infants are infected by age 2. Immunity is not durable; hence, reinfection occurs throughout life, although subsequent infections are nearly always mild. Certain populations (eg, premature infants, infants with chronic lung disease, and immunocompromised individuals) are at risk for severe morbidity and have higher risk of mortality. Infection is spread to the nose and eyes by large droplets and direct contact with secretions, and fomites may remain infectious for up to 12 hours. Nosocomial infection is common. The virus infects airway ciliated epithelial cells, spreading by the formation of syncytia. Cellular debris and inflammation cause airway obstruction, hyperinflation, localized atelectasis, wheezing, and impaired gas exchange. Both humoral and cellular immune response are critical to ending the acute infection, but wheezing and reactive airways may persist for as long as 5-10 years after acute infection. No cure exists for respiratory syncytial virus infection, but commonly employed palliative treatments include oxygen, inhaled beta(2) agonists, racemic epinephrine, dornase alfa, systemic and inhaled corticosteroids, inhaled ribavirin, and nasopharyngeal suctioning. Infants suffering severe lower airways disease may require mechanical ventilation. Prophylactic measures include rigorous infection control and administration of polyclonal (RSV-IGIV [respiratory syncytial virus - immunoglobulin intravenous]) and monoclonal (palivizumab) antibodies. The cost of the prophylactic antibody treatment is high; it is cost-effective for only the highest risk patients. Development of a vaccine remains far in the future. Application of evidence-based clinical practice guidelines is making both out-patient and in-patient therapy as effective and economical as possible.
Topics: Disease Management; Humans; Infant; Infant, Newborn; Respiratory Syncytial Virus Infections; Respiratory Therapy; Risk Factors; United States
PubMed: 12667273
DOI: No ID Found -
PloS One 2019Respiratory syncytial virus (RSV) is a common cause of respiratory tract infections in children and immunocompromised individuals. A multi-center surveillance of the...
Respiratory syncytial virus (RSV) is a common cause of respiratory tract infections in children and immunocompromised individuals. A multi-center surveillance of the epidemiologic and molecular characteristics of RSV circulating in Lebanon was performed. The attachment (G) and fusion (F) glycoproteins were analyzed and compared to those reported regionally and globally. 16% (83/519) of the nasopharyngeal swabs collected during the 2016/17 season tested positive for RSV; 50% (27/54) were RSV-A and 50% (27/54) were RSV-B. Phylogenetic analysis of the G glycoprotein revealed predominance of the RSVA ON1 genotype, in addition to two novel Lebanese genotype variants, hereby named LBA1 and LBA2, which descended from the ON1 and NA2 RSV-A genotypes, respectively. RSV-B strains belonged to BA9 genotype except for one BA10. Deduced amino acid sequences depicted several unique substitutions, alteration of glycosylation patterns and the emergence of palivizumab resistance among the Lebanese viruses. The emergence of ON1 and other novel genotypes that are resistant to palivizumab highlights the importance of monitoring RSV globally.
Topics: Adolescent; Adult; Antiviral Agents; Child; Child, Preschool; Drug Resistance, Viral; Female; Humans; Infant; Lebanon; Male; Middle Aged; Models, Molecular; Mutation; Palivizumab; Phylogeny; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Respiratory Tract Infections; Young Adult
PubMed: 30789963
DOI: 10.1371/journal.pone.0212687 -
EClinicalMedicine Nov 2021Despite passive immunization with palivizumab to select high-risk children under two years of age, the health and economic burden of respiratory syncytial virus (RSV)...
BACKGROUND
Despite passive immunization with palivizumab to select high-risk children under two years of age, the health and economic burden of respiratory syncytial virus (RSV) remains substantial. We evaluated the effectiveness and cost-effectiveness of immunization programs with new generations of RSV prophylactics, including long-acting monoclonal antibodies (LAMA) and maternal vaccines, in terms of reducing hospitalizations in Nunavik, a Canadian Arctic region.
METHODS
We developed an agent-based model of RSV transmission and parameterized it with the demographics and burden of RSV in Nunavik, Québec. We compared various immunization strategies, taking into account the costs associated with program delivery and calculating the incremental cost-effectiveness ratio (ICER) using quality-adjusted life-years (QALYs) gained as a measure of effectiveness. Scenario analyses included immunization with palivizumab and LAMA for infants under one year of age, and maternal vaccination in mild, moderate, and severe RSV seasons. Data were analysed from November 1, 2019 to May 1, 2021.
FINDINGS
We found that a Nunavik pilot program with palivizumab which included healthy full-term infants aged 0-2 months in addition to those considered high-risk for complicated RSV disease is not cost-effective, compared to offering palivizumab only to preterm/chronically ill infants under 1 year of age. Using LAMA as prophylaxis produces ICER values of CAD $39,414/QALY (95% Credible Interval [CrI]: $39,314-$40,017) in a mild season (moderately cost-effective) and CAD $5,255/QALY (95% CrI: $5,222-$5,307) in a moderate season (highly cost-effective). LAMA was a dominant (cost-saving with negative incremental costs and positive incremental effects) strategy in a severe RSV season. Maternal vaccination combined with immunization of preterm/chronically ill infants 3-11 months was also a dominant (cost-saving) strategy in all seasons.
INTERPRETATION
The switch from palivizumab in RSV immunization programs to new prophylactics would lead to significant savings, with LAMA being an effective strategy without compromising benefits in terms of reducing hospitalizations.
PubMed: 34622186
DOI: 10.1016/j.eclinm.2021.101141 -
Revue Medicale de Liege 2007Respiratory syncytial virus (RSV) is a serious pathogen causing significant morbidity, especially in premature infants and infants with chronic lung disease or... (Review)
Review
Respiratory syncytial virus (RSV) is a serious pathogen causing significant morbidity, especially in premature infants and infants with chronic lung disease or significant congenital heart disease. There is no specific treatment for RSV infection and the therapy is essentially supportive. Therefore, prophylaxis is the best strategy against RSV disease. Passive immunization with monoclonal antibodies (palivizumab) provides protection against severe RSV infection and significantly reduces hospitalizations in high-risk childrens. However, palizumab is an expensive drug and its use should be reserved for children at the highest risk of severe RSV disease.
Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antiviral Agents; Chemoprevention; Humans; Palivizumab; Respiratory Syncytial Virus Infections
PubMed: 17725198
DOI: No ID Found -
Health Technology Assessment... Dec 2008To systematically review the effectiveness and cost-effectiveness of palivizumab for the prevention of respiratory syncytial virus (RSV) in children and examine... (Review)
Review
OBJECTIVES
To systematically review the effectiveness and cost-effectiveness of palivizumab for the prevention of respiratory syncytial virus (RSV) in children and examine prognostic factors to determine whether subgroups can be identified with important differences in cost-effectiveness.
DATA SOURCES
Bibliographic databases were searched from inception to March 2007 for literature on the effectiveness and cost-effectiveness of prophylaxis with palivizumab.
REVIEW METHODS
The literature was systematically reviewed and current economic evaluations were analysed to identify which parameters were driving the different cost-effectiveness estimates. A probabilistic decision-analytical model was built to assess the cost-effectiveness of prophylaxis with palivizumab for children at risk of RSV infection and the parameters populated with the best estimates thought most applicable to the UK. We also constructed a new model, the Birmingham Economic Evaluation (BrumEE). Cost-effectiveness analyses were undertaken from both NHS and societal perspectives.
RESULTS
Two randomised controlled trials (RCTs) were identified. Prophylaxis with palivizumab for preterm infants without chronic lung disease (CLD) or children with CLD resulted in a 55% reduction in RSV hospital admission: 4.8% (48/1002) in the palivizumab group and 10.6% (53/500) in the no prophylaxis group (p = 0.0004). Prophylaxis with palivizumab was associated with a 45% reduction in hospitalisation rate RSV among children with coronary heart disease (CHD). Hospitalisation rates for RSV were 5.3% (34/639) in the palivizumab group and 9.7% (63/648) in the no prophylaxis group (p = 0.003). Of existing economic evaluations, 3 systematic reviews and 18 primary studies were identified. All the systematic reviews concluded that the potential costs of palivizumab were far in excess of any potential savings achieved by decreasing hospital admission rates, and that the use of palivizumab was unlikely to be cost-effective in all children for whom it is recommended, but that its continued use for particularly high-risk children may be justified. The incremental cost-effectiveness ratios (ICERs) of the primary studies varied 17-fold for life-years gained (LYG), from 25,800 pounds/LYG to 404,900 pounds/LYG, and several hundred-fold for quality-adjusted life-years (QALYs), from 3200 pounds/QALY to 1,489,700 pounds/QALY for preterm infants without CLD or children with CLD. For children with CHD, the ICER varied from 5300 pounds/LYG to 7900 pounds/LYG and from 7500 pounds/QALY to 68,700 pounds/QALY. An analysis of what led to the discrepant ICERs showed that the assumed mortality rate for RSV infection was the most important driver. The results of the BrumEE confirm that palivizumab does not reach conventional levels of cost-effectiveness in any of the licensed indications if used for all eligible children.
CONCLUSIONS
Prophylaxis with palivizumab is clinically effective for the reducing the risk of serious lower respiratory tract infection caused by RSV infection and requiring hospitalisation in high-risk children, but if used unselectively in the licensed population, the ICER is double that considered to represent good value for money in the UK. The BrumEE shows that prophylaxis with palivizumab may be cost-effective (based on a threshold of 30,000 pounds/QALY) for children with CLD when the children have two or more additional risk factors. Future research should initially focus on reviewing systematically the major uncertainties for patient subgroups with CLD and CHD and then on primary research to address the important uncertainties that remain.
Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antiviral Agents; Evidence-Based Medicine; Humans; Infant; Infant, Newborn; Palivizumab; Preventive Medicine; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; United Kingdom
PubMed: 19049692
DOI: 10.3310/hta12360