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Virology Sep 2023Monoclonal antibody (palivizumab), intravenous immune globulin (IGIV), or respiratory syncytial virus (RSV)-polyclonal-hyperimmune-globulin (RSV-IG as Respigam®,...
BACKGROUND
Monoclonal antibody (palivizumab), intravenous immune globulin (IGIV), or respiratory syncytial virus (RSV)-polyclonal-hyperimmune-globulin (RSV-IG as Respigam®, RI-001, RI-002) are used with ribavirin in RSV-infected immunocompromised patients, with debated efficacy. Palivizumab-resistance (PR) can arise during treatment of persistent infections in this population. RSV-IG may confer benefit in PR-RSV infection.
METHODS
RSV-IG [RI-001] was provided for an immunocompromised infant with RSV-pneumonitis refractory to ribavirin and palivizumab. RSV-neutralizing antibody, respiratory RSV load (qPCR), and F-gene-sequence-detection of PR was determined. Prophylactic RSV-IG [RI-002] or palivizumab was administered in a cotton-rat model infected with wild-type and PR-RSV. Lung RSV load and neutralizing antibody were measured.
RESULTS
As protective RI-001-neutralizing antibody titers waned in the infant, a subpopulation of PR-escape mutants were detected with a fatal RSV-burden in the lungs. In PR-RSV-infected cotton rats, prophylactic RI-002 reduced RSV-load in the lungs (2.45 vs 0.28 log PFU/g lung-tissue reduction, respectively, p < 0.05) and provided protective RSV-neutralizing antibody.
CONCLUSIONS
RSV-IG and ribavirin use in immunocompromised patients requires further study.
Topics: Humans; Palivizumab; Respiratory Syncytial Virus, Human; Respiratory Syncytial Virus Infections; Drug Resistance, Viral; Immunocompromised Host; Animals; Sigmodontinae; Lung; Immunoglobulins; Antibodies, Neutralizing; Female; Infant; Fatal Outcome; Precursor Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 37542818
DOI: 10.1016/j.virol.2023.07.007 -
Vaccine Aug 2023Respiratory syncytial virus contributes to significant global infant morbidity and mortality. We applied a previously developed statistical prediction model...
Respiratory syncytial virus contributes to significant global infant morbidity and mortality. We applied a previously developed statistical prediction model incorporating pre-pandemic RSV testing data and hospital admission data to estimate infant RSV-hospitalizations by birth month and prematurity, focused on infants aged <1 year. The overall predicted RSV-hospitalization incidence rates in infants <6 months were 32.7/1,000 child-years (95 % CI: 31.8, 33.5) and 3.1/1,000 child-years (95 % CI: 3.0, 3.1) in infants aged 6-<12 months. Predicted RSV-hospitalization rates for infants aged <6 months were highest for infants born in April/May. Predicted rates for preterm infants born 29-32 weeks gestation were highest in March-May, whereas infants born >33 weeks had peak RSV-hospitalization rates from May-June, similar to late preterm or term births. RSV-hospitalization rates in the pre-pandemic era were highly seasonal, and seasonality varied with degree of prematurity. Accurate estimates of RSV-hospitalization in high-risk sub-groups are essential to understand preventable burden of RSV especially given the current prevention landscape.
Topics: Humans; Infant, Newborn; Infant; Infant, Premature; Incidence; Respiratory Syncytial Virus Infections; Western Australia; Seasons; Respiratory Syncytial Virus, Human; Hospitalization; Palivizumab; Antiviral Agents
PubMed: 37474407
DOI: 10.1016/j.vaccine.2023.07.014 -
Journal of the Pediatric Infectious... Aug 2023In children with congenital heart disease and/or chronic lung disease entering their second respiratory syncytial virus (RSV) season, 200 mg nirsevimab had a similar...
In children with congenital heart disease and/or chronic lung disease entering their second respiratory syncytial virus (RSV) season, 200 mg nirsevimab had a similar safety profile to that of palivizumab and resulted in nirsevimab serum exposures associated with efficacy in healthy infants, supporting efficacy in this population at risk of severe RSV disease.
Topics: Infant; Child; Humans; Antibodies, Monoclonal; Antiviral Agents; Seasons; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Lung Diseases
PubMed: 37466917
DOI: 10.1093/jpids/piad052 -
American Family Physician Jul 2023Bronchiolitis is the most common lower respiratory tract infection in young children. Respiratory syncytial virus (RSV) is the most common viral cause of bronchiolitis.... (Review)
Review
Bronchiolitis is the most common lower respiratory tract infection in young children. Respiratory syncytial virus (RSV) is the most common viral cause of bronchiolitis. RSV is spread through respiratory droplets, and the number of cases varies with season. For most patients, standard precautions (e.g., hand hygiene, surface cleaning, avoiding contact with sick individuals) are recommended. However, prophylaxis with palivizumab may be considered for infants at high risk. Initial symptoms occur after an incubation period of four to six days and include rhinorrhea, congestion, sneezing, and fever. Signs of lower respiratory tract involvement may follow and include cough, tachypnea, retractions, difficulty feeding, and accessory muscle use. Diagnosis is typically clinical; routine use of radiography or viral testing is not recommended. Treatment of RSV bronchiolitis is mainly supportive. Oxygen saturation should be maintained above 90%. Hydration and nutrition should be maintained by nasogastric or intravenous routes, if needed. Therapies such as bronchodilators, epinephrine, nebulized hypertonic saline, corticosteroids, antibiotics, and chest physiotherapy are not recommended. Although most episodes of RSV bronchiolitis are self-limited, some children have an increased risk of asthma later in life.
Topics: Child; Child, Preschool; Humans; Infant; Bronchiolitis; Bronchodilator Agents; Palivizumab; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses
PubMed: 37440737
DOI: No ID Found -
Canada Communicable Disease Report =... Jul 2022Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infection in young children worldwide. Underlying health conditions, especially...
Summary of the National Advisory Committee on Immunization (NACI) statement update on the recommended use of palivizumab to reduce complications of respiratory syncytial virus infection in infants.
BACKGROUND
Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infection in young children worldwide. Underlying health conditions, especially premature birth, chronic lung disease and congenital heart disease, predispose to severe RSV illness. The only means of prophylaxis against RSV disease is passive prophylaxis with the monoclonal antibody, palivizumab (PVZ) (Synagis). The National Advisory Committee on Immunization (NACI) published a statement for PVZ use in 2003. The purpose of this article is to update previous NACI recommendations for the use of PVZ, taking into consideration recent data on RSV burden of illness, effectiveness of PVZ in infants at risk of more severe RSV disease and economic implications of PVZ use.
METHODS
The NACI Working Group and external experts performed systematic literature reviews on three topics to support updated NACI guidance: 1) RSV burden of disease; 2) PVZ effectiveness; and 3) cost effectiveness of PVZ prophylaxis. Full details and results are presented in the statement and supporting documents.
RESULTS
Respiratory syncytial virus hospitalization (RSVH) rates are highest in children younger than one year of age and especially in the first two months of life. In various populations of infants at risk of severe RSV infection, PVZ prophylaxis is associated with reductions of 38%-86% in the risk of RSVH. Only rare cases of anaphylaxis have been reported after decades of use. Palivizumab is expensive and only cost-saving in rare scenarios.
CONCLUSION
Updated NACI recommendations on use of PVZ for the prevention of complications of RSV in infants are now available.
PubMed: 37426290
DOI: 10.14745/ccdr.v48i78a08 -
Frontiers in Pediatrics 2023Preterm infants born between 33 and 35 weeks of gestational age (wGA) have been considered a "major underserved population" and ineligible to receive palivizumab (PLV),...
BACKGROUND
Preterm infants born between 33 and 35 weeks of gestational age (wGA) have been considered a "major underserved population" and ineligible to receive palivizumab (PLV), the only drug authorized to date for respiratory syncytial virus (RSV) prophylaxis, by current international guidelines. In Italy, such a vulnerable population is currently eligible for prophylaxis, and, in our region, specific risk factors are taken into consideration (SIN score) to target prophylaxis for those at highest risk. Whether the adoption of less or more restrictive eligibility criteria for PLV prophylaxis would translate into differences in bronchiolitis and hospitalization incidence is not known.
MATERIALS AND METHODS
A retrospective analysis was conducted in 296 moderate-to-late preterm infants (born between 33 and 35 weeks) who were being considered for prophylaxis in two epidemic seasons: 2018-2019 and 2019-2020. The study participants were categorized according to both the SIN score and the Blanken risk scoring tool (BRST), which was found to reliably predict RSV-associated hospitalization in preterm infants on the basis of three risk factor variables.
RESULTS
Based on the SIN score, approximately 40% of infants (123/296) would meet the criteria to be eligible for PLV prophylaxis. In contrast, none of the analyzed infants would be considered eligible for RSV prophylaxis on the basis of the BRST. A total of 45 (15.2%) bronchiolitis diagnoses were recorded on average at 5 months of age in the overall population. Almost seven out of 10 (84/123) patients exhibiting ≥3 risk factors to be eligible for RSV prophylaxis according to SIN criteria would not be receiving PLV if they were categorized on the basis of the BRST. Bronchiolitis occurrence in patients with a SIN score ≥3 was approximately 2.2 times more likely than that in patients with a SIN score <3. PLV prophylaxis has been associated with a 91% lower risk of requiring a nasal cannula.
CONCLUSION
Our work further supports the need for targeting late preterm infants for RSV prophylaxis and calls for an appraisal of the current eligibility criteria for PLV treatment. Therefore, adopting less restrictive criteria may ensure a comprehensive prophylaxis of the eligible subjects, thus sparing them from avoidable short- and long-term consequences of RSV infection.
PubMed: 37360357
DOI: 10.3389/fped.2023.1154518 -
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 -
Indian Journal of Pediatrics Dec 2023Respiratory syncytial virus (RSV) is a highly contagious respiratory virus that can cause mild to severe illness in children. It is the leading cause of lower... (Review)
Review
Respiratory syncytial virus (RSV) is a highly contagious respiratory virus that can cause mild to severe illness in children. It is the leading cause of lower respiratory tract infections (LRTI) in children under the age of one year, and it can also affect older children and adults, especially those with underlying medical conditions. In the post-COVID period, there seems to be an increase in the incidence, possibly due to 'immunity debt'. Symptoms of RSV infection in children may include fever, runny nose, and cough. In severe cases, it can lead to bronchiolitis (inflammation of the small airways in the lungs) or pneumonia (infection of the lungs). Most children with RSV infection recover within a week or two, but some may require hospitalization, especially those who are premature or have underlying medical conditions. As there is no specific treatment for RSV infection, supportive care is the mainstay of management. In severe cases, oxygen therapy or mechanical ventilation may be necessary. High flow nasal cannula seems to be beneficial. There have been promising advances in development of RSV vaccines; few trials in adults and pregnant women have reported encouraging results. The US FDA has approved two RSV vaccines for use in older adults (GSK's Arexvy and Pfizer's ABRYSVO).
Topics: Pregnancy; Child; Humans; Female; Infant; Aged; Adolescent; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus Vaccines; Respiratory Syncytial Virus, Human; Bronchiolitis; Lung
PubMed: 37326948
DOI: 10.1007/s12098-023-04613-w -
Italian Journal of Pediatrics Jun 2023Bronchiolitis is a major cause of hospitalization in infants, particularly in the first six months of life, with approximately 60-80% of admissions due to respiratory...
BACKGROUND
Bronchiolitis is a major cause of hospitalization in infants, particularly in the first six months of life, with approximately 60-80% of admissions due to respiratory syncytial virus (RSV) infection. Currently, no prophylactic options are available for healthy infants. The present study aimed at describing the demographic, clinical, and epidemiological characteristics of infants hospitalized for bronchiolitis in the Apulia region of Italy in 2021.
METHODS
From January to December 2021, data on children aged 0-12 months admitted for bronchiolitis in nine neonatal or pediatric units covering 61% of pediatric beds of hospitals in the Apulia region of Italy were analyzed. Demographic data, comorbidities, need for oxygen support, length of hospital stay, palivizumab administration, and outcomes were collected. For the purpose of the analysis, patients were divided into those aged 0-3 months and > 3 months. A multivariate logistic regression model was used to explore associations between the need for oxygen support and sex, age, comorbidities, history of prematurity, length of hospital stay, and palivizumab administration.
RESULTS
This study included 349 children aged 0-12 months admitted for bronchiolitis, with a peak of hospitalization in November (7.4 cases/1,000 children). Of these patients, 70.5% were RSV positive, 80.2% were aged 0-3 months, and 73.1% required oxygen support. Moreover, 34.9% required observation in the sub-intensive care unit, and 12.9% in the intensive care unit. Of the infants who required intensive care, 96.9% were aged 0-3 months and 78.8% were born at term. Three patients required mechanical ventilation and one, who required Extra Corporeal Membrane Oxygenation, died. Children aged 0-3 months were more likely to show dyspnea, need oxygen support, and have a longer hospital stay.
CONCLUSIONS
The present study showed that almost all of the children who required intensive care support were aged ≤ 3 months and most were born at term. Therefore, this age group remains the highest risk group for severe bronchiolitis. Preventive measures such as single-dose monoclonal antibody immunoprophylaxis, and maternal and childhood vaccination against RSV, may reduce the high public health burden of bronchiolitis.
Topics: Infant, Newborn; Infant; Humans; Child; Palivizumab; Antiviral Agents; Antibodies, Monoclonal, Humanized; Hospitalization; Bronchiolitis; Respiratory Syncytial Virus Infections; Italy
PubMed: 37280662
DOI: 10.1186/s13052-023-01455-2 -
Viruses Apr 2023The respiratory syncytial virus (RSV) causes significant respiratory disease in young infants and the elderly. Immune prophylaxis in infants is currently limited to...
The respiratory syncytial virus (RSV) causes significant respiratory disease in young infants and the elderly. Immune prophylaxis in infants is currently limited to palivizumab, an anti-RSV fusion (F) protein monoclonal antibody (mAb). While anti-F protein mAbs neutralize RSV, they are unable to prevent aberrant pathogenic responses provoked by the RSV attachment (G) protein. Recently, the co-crystal structures of two high-affinity anti-G protein mAbs that bind the central conserved domain (CCD) at distinct non-overlapping epitopes were solved. mAbs 3D3 and 2D10 are broadly neutralizing and block G protein CX3C-mediated chemotaxis by binding antigenic sites γ1 and γ2, respectively, which is known to reduce RSV disease. Previous studies have established 3D3 as a potential immunoprophylactic and therapeutic; however, there has been no similar evaluation of 2D10 available. Here, we sought to determine the differences in neutralization and immunity to RSV Line19F infection which recapitulates human RSV infection in mouse models making it useful for therapeutic antibody studies. Prophylactic (24 h prior to infection) or therapeutic (72 h post-infection) treatment of mice with 3D3, 2D10, or palivizumab were compared to isotype control antibody treatment. The results show that 2D10 can neutralize RSV Line19F both prophylactically and therapeutically, and can reduce disease-causing immune responses in a prophylactic but not therapeutic context. In contrast, 3D3 was able to significantly ( < 0.05) reduce lung virus titers and IL-13 in a prophylactic and therapeutic regimen suggesting subtle but important differences in immune responses to RSV infection with mAbs that bind distinct epitopes.
Topics: Mice; Humans; Animals; Aged; Palivizumab; Antibodies, Viral; Viral Fusion Proteins; Respiratory Syncytial Virus, Human; Respiratory Syncytial Virus Infections; Antibodies, Monoclonal; Epitopes
PubMed: 37243153
DOI: 10.3390/v15051067