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ClinicoEconomics and Outcomes Research... 2014Respiratory syncytial virus (RSV) is an important respiratory pathogen in infants and children worldwide. Although RSV typically causes mild upper respiratory... (Review)
Review
Respiratory syncytial virus (RSV) is an important respiratory pathogen in infants and children worldwide. Although RSV typically causes mild upper respiratory infections, it frequently causes severe morbidity and mortality, especially in premature infants and children with other chronic diseases. Treatment of RSV is limited by a lack of effective antiviral treatments; however, ribavirin has been used in complicated cases, along with the addition of intravenous immune globulin in specific patients. Vaccination strategies for RSV prevention are heavily studied, but only palivizumab (Synagis(®)) has been approved for use in the United States in very select patient populations. Research is ongoing in developing additional vaccines, along with alternative therapies that may help prevent or decrease the severity of RSV infections in infants and children. To date, we have not seen a decrement in RSV morbidity and mortality with our current options; therefore, there is a clear need for novel RSV preventative and therapeutic strategies. In this review, we discuss the current and evolving trends in RSV treatment for infants and children.
PubMed: 24812523
DOI: 10.2147/CEOR.S60710 -
Respiratory Research 2002Respiratory syncytial virus (RSV) infects nearly all children by age 2 years, and it causes considerable illness and death in certain high-risk pediatric populations.... (Review)
Review
Respiratory syncytial virus (RSV) infects nearly all children by age 2 years, and it causes considerable illness and death in certain high-risk pediatric populations. Historically, treatment for RSV has been symptomatic, and developing a safe and effective vaccine has been a challenge. Therefore, research efforts have turned to passive immunization as the best option to control RSV. Palivizumab, a genetically engineered humanized monoclonal antibody, has been shown to reduce RSV-related hospitalizations significantly, with few adverse effects. It was approved for use in high-risk children in the USA in 1998 and in Europe in 1999; it is now approved for use in more than 45 countries. The efficacy and safety of palivizumab continue to be supported by both clinical trial and outcomes data.
Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antiviral Agents; Humans; Immunization, Passive; Immunoglobulins; Palivizumab; Respiratory Syncytial Virus Infections
PubMed: 12119055
DOI: 10.1186/rr187 -
Drugs in Context 2015The peak season of respiratory syncytial virus (RSV) infections in warmer climates may extend beyond the typical five-month RSV season of temperate regions. Additional...
BACKGROUND
The peak season of respiratory syncytial virus (RSV) infections in warmer climates may extend beyond the typical five-month RSV season of temperate regions. Additional monthly doses of palivizumab may be necessary in warmer regions to protect children at high risk for serious infection by the RSV.
METHODS
In a Phase II, single-arm, single-center, non-comparative, open-label, prospective study conducted in Saudi Arabia, children at high risk for RSV infection received up to seven monthly injections of palivizumab (15 mg/kg) during the 2000-2001 RSV season. Key enrollment criteria were no previous exposure to palivizumab and gestational age ≤35 weeks, ≤6 months of age at enrollment, or chronic lung disease and ≤24 months of age at enrollment. We wished to assess the safety, immunogenicity, and pharmacokinetics of palivizumab as an extended seven-dose regimen.
RESULTS
Of 18 enrolled patients, 17 patients received seven palivizumab injections. Seven adverse events (AEs) occurred in five patients. Bronchiolitis was the most commonly reported AE. Six serious AEs occurred in four patients. No AEs were considered related to palivizumab. Trough levels of palivizumab in serum were >40 μg/mL in most patients after the first injection and in 16/18 and 14/17 patients after the fourth and sixth injections, respectively. Except for one patient at one visit, the anti-palivizumab titer was <1:10 at all visits.
CONCLUSION
These data suggest that an extended palivizumab regimen of up to seven monthly doses during the RSV season exhibited an acceptable safety profile in children at high risk for RSV infection in Saudi Arabia.
PubMed: 25767550
DOI: 10.7573/dic.212270 -
F1000Research 2019Severe respiratory syncytial virus (RSV) lower respiratory tract illness (LRTI) in infants has proven challenging to prevent. In the last 50 years, conceptually... (Review)
Review
Severe respiratory syncytial virus (RSV) lower respiratory tract illness (LRTI) in infants has proven challenging to prevent. In the last 50 years, conceptually different approaches failed to evolve into viable preventive alternatives for routine use. Inactivated RSV vaccine (that is, formalin-inactivated RSV) elicited severe LRTI in RSV-infected toddlers pre-immunized as infants; early purified F protein approaches in pregnant women failed to elicit sufficient immunity more than a decade ago; a second-generation monoclonal antibody (mAb) of high potency against the virus (that is, motavizumab) caused severe adverse reactions in the skin, and owing to lack of efficacy against RSV subgroup B, an extended half-life mAb targeting site V in the RSV fusion protein (that is, REG2222) did not meet its primary endpoint. In the meantime, two protein F vaccines failed to prevent medically attended LRTI in the elderly. However, palivizumab and the recent results of the Novavax maternal immunization trial with ResVax demonstrate that severe RSV LRTI can be prevented by mAb and by maternal immunization (at least to a certain extent). In fact, disease prevention may also decrease the rates of recurrent wheezing and all-cause pneumonia for at least 180 days. In this review, we discuss the history of RSV vaccine development, previous and current vaccine strategies undergoing evaluation, and recent information about disease burden and its implications for the effects of successful preventive strategies.
Topics: Aged; Antibodies, Monoclonal; Child, Preschool; Female; Humans; Infant; Palivizumab; Pregnancy; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; Respiratory System; Viral Vaccines
PubMed: 31105933
DOI: 10.12688/f1000research.18749.1 -
Newborn (Clarksville, Md.) 2023Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infections in young infants. It is an enveloped, single-stranded, nonsegmented,...
Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infections in young infants. It is an enveloped, single-stranded, nonsegmented, negative-strand RNA virus, a member of the family Pneumoviridae. Globally, RSV is responsible for 2.3% of deaths among neonates 0-27 days of age. Respiratory syncytial virus infection is most common in children aged below 24 months. Neonates present with cough and fever. Respiratory syncytial virus-associated wheezing is seen in 20% infants during the first year of life of which 2-3% require hospitalization. Reverse transcriptase polymerase chain reaction (RT-PCR) gives fast results and has higher sensitivity compared with culture and rapid antigen tests and are not affected by passively administered antibody to RSV. Therapy for RSV infection of the LRT is mainly supportive, and preventive measures like good hygiene and isolation are the mainstay of management. Standard precautions, hand hygiene, breastfeeding and contact isolation should be followed for RSV-infected newborns. Recent AAP guidelines do not recommend pavilizumab prophylaxis for preterm infants born at 29-35 weeks without chronic lung disease, hemodynamically significant congenital heart disease and coexisting conditions. RSV can lead to long-term sequelae such as wheezing and asthma, associated with increased healthcare costs and reduced quality of life.
PubMed: 38348152
DOI: 10.5005/jp-journals-11002-0073 -
BMJ Open Jul 2019Childhood respiratory syncytial virus (RSV) infection is a global phenomenon that can lead to fatal respiratory illness. Palivizumab is a drug that is routinely used in...
INTRODUCTION
Childhood respiratory syncytial virus (RSV) infection is a global phenomenon that can lead to fatal respiratory illness. Palivizumab is a drug that is routinely used in affluent countries as a prophylaxis against RSV infection; nevertheless, breakthrough infections are often reported. In light of new findings on potential RSV resistance to palivizumab, an up-to-date synthesis of evidence on effectiveness is needed. Furthering existing reviews, a broadened scope to better reflect effectiveness in a 'real world' clinical context is also important. This systematic review and meta-analysis will enhance our understanding of the effectiveness of palivizumab in varying populations of children. Findings from this review will inform recommendations for best practices regarding palivizumab use for childhood RSV infection as well as research priorities in RSV vaccine development.
METHODS AND ANALYSIS
We will conduct a systematic review of primary population-based studies that examine the incidence of palivizumab breakthrough infections in children, published between 1997 to present. In collaboration with a research librarian, four electronic databases (MEDLINE, Embase, Cochrane Library, Web of Science) and additional sources will be searched. Study screening and quality assessment will be performed in duplicate. Data will be extracted by one reviewer, with partial and random verification by a second reviewer. The primary outcomes to assess breakthrough RSV infection will be hospitalisation, length of stay and the need for intensive care unit admission and mechanical ventilation in children receiving palivizumab. The secondary outcome will be RSV-associated mortality. We will conduct a meta-analysis using pooled effectiveness data, and include subgroup analyses by patient comorbidities and drug compliance. Sensitivity analyses for risk of bias and study design will also be performed.
ETHICS AND DISSEMINATION
This systematic review will only include data from previously published literature and is therefore exempt from ethics approval. Final results will be disseminated through peer-reviewed publication and presented at academic conferences and scientific meetings engaging paediatric researchers and healthcare providers. Should findings from this review necessitate updates to current clinical practice guidelines, we intend to establish a working group to engage relevant health administrators and decision makers.
PROSPERO REGISTRATION NUMBER
CRD42019122120.
Topics: Antiviral Agents; Child; Hospitalization; Humans; Intensive Care Units; Meta-Analysis as Topic; Palivizumab; Preventive Medicine; Research Design; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; Systematic Reviews as Topic
PubMed: 31340973
DOI: 10.1136/bmjopen-2019-029832 -
International Journal of Pediatrics 2014Infection with respiratory syncytial virus (RSV) is one of the major causes globally of childhood respiratory morbidity and hospitalization. Palivizumab, a humanized... (Review)
Review
Infection with respiratory syncytial virus (RSV) is one of the major causes globally of childhood respiratory morbidity and hospitalization. Palivizumab, a humanized monoclonal antibody, has been recommended for high risk infants to prevent severe RSV-associated respiratory illness. This recommendation is based on evidence of efficacy when used under clinical trial conditions. However the real-world effectiveness of palivizumab outside of clinical trials among different patient populations is not well established. We performed a systematic review focusing on postlicensure observational studies of the protective effect of palivizumab prophylaxis for reducing RSV-associated hospitalizations in infants and children at high risk of severe infection. We searched studies published in English between 1 January 1999 and August 2013 and identified 420 articles, of which 20 met the inclusion criteria. This review supports the recommended use of palivizumab for reducing RSV-associated hospitalization rates in premature infants born at gestational age < 33 weeks and in children with chronic lung and heart diseases. Data are limited to allow commenting on the protective effect of palivizumab among other high risk children, including those with Down syndrome, cystic fibrosis, and haematological malignancy, indicating further research is warranted in these groups.
PubMed: 25548575
DOI: 10.1155/2014/571609 -
BMJ Paediatrics Open 2021In Italy, reimbursement restrictions regarding palivizumab prophylaxis approved in 2016 have been revoked in 2017, restoring use in infants with Gestational Age (GA) >29...
In Italy, reimbursement restrictions regarding palivizumab prophylaxis approved in 2016 have been revoked in 2017, restoring use in infants with Gestational Age (GA) >29 weeks. Respiratory Syncytial Virus (RSV) hospitalisations and prevalence of palivizumab use in infants aged <6 months during five seasons (2014-2019), were considered according to different GA. Although RSV hospitalisations rate showed no significant changes, during different seasons in all GA, lower prevalence of palivizumab use in 2016 (0.8% vs 0.3%), returned to a higher level following the revoke of restrictions. Changes in reimbursement criteria were not associated with neonatal RSV hospitalisations rate but with a significant impact on palivizumab use.
Topics: Antibodies, Monoclonal, Humanized; Antiviral Agents; Hospitalization; Humans; Infant; Infant, Newborn; Palivizumab; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Retrospective Studies
PubMed: 33748434
DOI: 10.1136/bmjpo-2020-000985 -
Microbiology Spectrum Aug 2014Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract disease in infants and young children. Initial efforts to develop a vaccine to prevent... (Review)
Review
Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract disease in infants and young children. Initial efforts to develop a vaccine to prevent RSV lower respiratory tract disease in children were halted because of serious adverse events that occurred when children were infected with RSV following vaccination, including vaccine-related deaths. Subsequently, a major focus for researchers was to understand what led to these adverse events. Investment in a vaccine for RSV continues, and new strategies are under development. Success to prevent RSV disease was met by the development of immunoprophylaxis, first with intravenous immunoglobulin and then with recombinant monoclonal antibody. The story of immunoprophylaxis for RSV includes the first-in-class use of antibody technology for infectious disease, and palivizumab currently remains the only way to prevent serious lower respiratory tract disease due to RSV infection.
Topics: Antibodies, Monoclonal; Antibodies, Viral; Chemoprevention; Humans; Immunoglobulins, Intravenous; Palivizumab; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus Vaccines; Respiratory Syncytial Viruses; Vaccination
PubMed: 26104207
DOI: 10.1128/microbiolspec.AID-0014-2014 -
PloS One 2023Since the last Italian cost-utility assessment of palivizumab in 2009, new data on the burden of respiratory syncytial virus (RSV) and an International Risk Scoring Tool...
A new cost-utility analysis assessing risk factor-guided prophylaxis with palivizumab for the prevention of severe respiratory syncytial virus infection in Italian infants born at 29-35 weeks' gestational age.
Since the last Italian cost-utility assessment of palivizumab in 2009, new data on the burden of respiratory syncytial virus (RSV) and an International Risk Scoring Tool (IRST) have become available. The objective of this study was to provide an up-to-date cost-utility assessment of palivizumab versus no prophylaxis for the prevention of severe RSV infection in otherwise healthy Italian infants born at 29-31 weeks' gestational age (wGA) infants and those 32-35wGA infants categorized as either moderate- or high-risk of RSV-hospitalization (RSVH) by the IRST. A decision tree was constructed in which infants received palivizumab or no prophylaxis and then could experience: i) RSVH; ii) emergency room medically-attended RSV-infection (MARI); or, iii) remain uninfected/non-medically attended. RSVH cases that required intensive care unit admission could die (0.43%). Respiratory morbidity was considered in all surviving infants up to 18 years of age. Hospitalization rates were derived from Italian data combined with efficacy from the IMpact-RSV trial. Palivizumab costs were calculated from vial prices (50mg: €490.37 100mg: €814.34) and Italian birth statistics combined with a growth algorithm. A lifetime horizon and healthcare and societal costs were included. The incremental cost-utility ratio (ICUR) was €14814 per quality-adjusted life year (QALY) gained in the whole population (mean: €15430; probability of ICUR being <€40000: 0.90). The equivalent ICURs were €15139 per QALY gained (€15915; 0.89) for 29-31wGA infants and €14719 per QALY gained (€15230; 0.89) for 32-35wGA infants. The model was most sensitive to rates of long-term sequelae, utility scores, palivizumab cost, and palivizumab efficacy. Palivizumab remained cost-effective in all scenario analyses, including a scenario wherein RSVH infants received palivizumab without a reduction in long-term sequelae and experienced a 6-year duration of respiratory morbidity (ICUR: €27948 per QALY gained). In conclusion, palivizumab remains cost-effective versus no prophylaxis in otherwise healthy Italian preterm infants born 29-35wGA. The IRST can help guide cost-effective use of palivizumab in 32-35wGA infants.
Topics: Infant, Newborn; Infant; Humans; Palivizumab; Respiratory Syncytial Virus Infections; Cost-Benefit Analysis; Gestational Age; Antiviral Agents; Infant, Premature; Antibodies, Monoclonal, Humanized; Risk Factors; Respiratory Syncytial Virus, Human; Hospitalization; Italy
PubMed: 37561741
DOI: 10.1371/journal.pone.0289828