INTRODUCTION — Respiratory syncytial virus (RSV) causes acute respiratory tract illness in persons of all ages. The clinical manifestations vary with age, health status, and whether the infection is primary or secondary.
The prevention of RSV infection in infants and children will be discussed here. The epidemiology, microbiology, clinical manifestations, diagnosis, and treatment of RSV infection and bronchiolitis are discussed separately.
GENERAL MEASURES — Transmission of RSV predominantly occurs through inoculation of nasopharyngeal or ocular mucous membranes after direct contact with virus-containing secretions or fomites. General measures to prevent RSV infection are focused on decreasing inoculation. They include [1,2]:
●Hand washing in all settings, particularly when high-risk infants are at risk for exposure to respiratory infections from older siblings [3,4]
●Practicing cough hygiene (eg, covering the mouth and nose with a tissue, upper sleeve, or elbow when coughing or sneezing; immediately disposing of the tissue in a waste receptacle; washing hands)
●Avoidance of exposure to tobacco and other smoke (see "Control of secondhand smoke exposure", section on 'Strategies to prevent secondhand smoke exposure')
●Restricting participation in childcare during RSV season for high-risk infants (if possible)
INFECTION CONTROL IN THE HEALTH CARE SETTING — RSV is highly contagious and can cause serious health care-associated infections, particularly in high-risk patients (eg, those with congenital heart or lung disease, hematopoietic cell or solid organ transplant, older adults with multiple underlying conditions). Rapid diagnosis of RSV infection is essential for implementation of measures to prevent health care-associated infection in high-risk patients. (See "Respiratory syncytial virus infection: Clinical features and diagnosis", section on 'Diagnosis'.)
The types of infection control precautions are determined by the setting:
●Inpatient and ambulatory settings – In both inpatient and ambulatory settings the Centers for Disease Control and Prevention recommends standard and contact precautions for prevention of RSV [5,6]. Hand washing and appropriate use of gloves are probably the most important infection control measures, but surgical mask, eye protection, and disposable gowns for health care providers should be used when there is a chance of exposure to infectious respiratory secretions [5-10]. (See "Infection prevention: Precautions for preventing transmission of infection".)
●Inpatient settings – In the inpatient setting, it is particularly important to avoid exposing immunocompromised children (eg, those with allogeneic hematopoietic cell transplantation) to RSV. In addition to standard and contact precautions, isolation of patients in private rooms or in rooms with other RSV-infected patients (cohorting patients) and limited transport of patients from their rooms also are recommended [5,11-13]. During outbreaks, personnel caring for RSV-infected patients should be restricted from caring for uninfected patients as often as possible (cohorting personnel).
Health care personnel and visitors with upper respiratory tract infections should be restricted from contact with high-risk patients as much as is practical, especially during the peak RSV transmission months [11,13,14]. Health care personnel should have continuing education about the symptoms, epidemiology, diagnosis, and transmission of RSV. (See "Respiratory syncytial virus infection: Clinical features and diagnosis".)
PALIVIZUMAB IMMUNOPROPHYLAXIS — Palivizumab is a humanized monoclonal antibody against the RSV F glycoprotein, which is highly conserved among various isolates. It was licensed in 1998 for the prevention of serious RSV lower respiratory tract disease in children at high risk of RSV disease . Compared with RSV immune globulin, which is no longer available, palivizumab is easier to administer (intramuscular [IM] rather than intravenous) and does not interfere with response to routine immunization with live virus vaccines (eg, measles, mumps, rubella, varicella) .
Efficacy and effectiveness — The efficacy of palivizumab has been demonstrated in randomized trials. In a meta-analyses of three prelicensure randomized trials comparing palivizumab prophylaxis with placebo in 2831 high-risk infants with bronchopulmonary dysplasia (BPD) or other high-risk conditions (eg, ≤35 weeks' gestation, congenital heart disease [CHD]), palivizumab reduced RSV hospitalizations from 101 to 50 per 1000 (relative risk [RR] 0.49, 95% CI 0.37-0.64) and intensive care unit admissions from 34 to 17 per 1000 (RR 0.5, 95% CI 0.3 to 0.81 in two studies with 2789 patients) without increasing the risk of adverse events .
Postlicensure surveillance indicates that RSV-associated hospitalization rates among high-risk infants who receive palivizumab are similar to or lower than the RSV-associated hospitalization rates described in prelicensure trials, supporting effectiveness outside the trial setting [16,18-24]. However, in cross-sectional analysis, all-cause hospitalization rates for bronchiolitis in the United States declined between 2000 and 2016 (from 17.9 to 13.5 per 1000 person years) . As the RSV hospitalization rate among children who do not receive palivizumab decreases, the magnitude of the benefit of palivizumab declines, increasing the number of children who need to be treated to prevent one hospitalization as well as the cost-to-benefit ratio .
Indications for palivizumab — Our suggestions for palivizumab prophylaxis are generally consistent with those of the American Academy of Pediatrics (AAP), which were reaffirmed in 2019 (table 1) [26,27]. However, recommendations for and availability of palivizumab prophylaxis vary geographically. (See 'Society guideline links' below.)
Prematurity with bronchopulmonary dysplasia — The terminology for and definition for BPD (also known as neonatal chronic lung disease) have changed over time. For the purpose of palivizumab prophylaxis, we use the definition for neonatal chronic lung disease provided in the AAP guidelines: gestational age <32 weeks, 0 days and a requirement for supplementation oxygen for the first 28 days after birth . (See "Bronchopulmonary dysplasia (BPD): Clinical features and diagnosis", section on 'Definitions and severity of BPD'.)
●Younger than one year of age at the start of RSV season, or
●Age 12 through 23 months and required medical therapy (eg, supplemental oxygen, glucocorticoids, diuretics) for BPD within six months of the start of RSV season
Palivizumab decreases the risk of hospitalization for these infants with few adverse effects but may be associated with high out-of-pocket costs.
The benefits of palivizumab for preterm infants with BPD have been demonstrated in randomized trials [17,29]. In subgroup analysis of a prelicensure multicenter randomized trial, palivizumab decreased the absolute rate of hospitalization in 762 infants with BPD from 12.8 percent to 7.9 percent (relative reduction of 39 percent, 95% CI 20-58 percent) . In a systematic review of prospective comparative studies in premature infants with BPD [29,30], palivizumab administration was associated with decreased mean weighted rate of hospitalization (6.2 versus 17.6 percent, range of absolute reduction 4.9 to 14.2 percent; relative reduction of 65 percent, range 38 to 72 percent) .
●We suggest that palivizumab be administered to preterm infants without BPD who were born at <29 weeks of gestation and are younger than 12 months of age at the start of RSV season.
●For preterm infants without BPD who were born between 29 and 32 weeks' gestation and who are younger than 12 months of age at the start of RSV season, the authors of this topic review make decisions on a case-by-case basis after discussing the potential benefits and costs with the infant's caregiver(s). Additional factors to be considered in the decision include risk factors for severe disease (eg, age <4 months during peak RSV season, childcare attendance, older siblings in the home, parental smoking, prevalence of RSV in the community) and out-of-pocket costs [3,32-34]. (See "Respiratory syncytial virus infection: Clinical features and diagnosis", section on 'Risk factors' and 'Native American and Alaska Native infants' below.)
Recommendations from professional societies regarding palivizumab prophylaxis in preterm infants without BPD who were born between 29 and 32 weeks' gestation are inconsistent [26,34]. (See 'Society guideline links' below.)
In subgroup analysis of a multicenter randomized trial that compared palivizumab and placebo, palivizumab decreased the rate of hospitalization in 740 infants with prematurity without BPD (1.8 versus 8.1 percent) ; further subgroup analysis according to gestational age was not performed. In a systematic review of prospective comparative studies in premature infants born at <35 weeks' gestation (with or without BPD) [29,30,35,36], palivizumab administration was associated with decreased mean weighted rate of RSV hospitalization (3 versus 9.5 percent; range of absolute risk reduction 0.2-14.7 percent) .
Published studies do not provide a clear threshold of prematurity for which the benefits of palivizumab are definitive [31,37,38]. Several population-based and cohort studies suggest that the risk of RSV hospitalization among infants born at <29 weeks' gestation is two to four times greater than in term infants, but the risk of RSV hospitalization among infants born at ≥32 weeks' gestation is similar to that in term infants [39-43]. Some observational studies have noted an association between decreased palivizumab use and increased RSV hospitalization rate, severity, and/or cost among preterm infants born at 29 to 35 weeks' gestation [44-50], but the findings are inconsistent [51-53].
Other potential target groups — We consider palivizumab prophylaxis on a case-by-case basis for children in other target groups who are at increased risk for RSV-associated morbidity or who have limited access to care for severe respiratory illness (table 1).
Congenital heart disease — Decisions regarding palivizumab prophylaxis for children with CHD should be individualized according to the degree of cardiovascular compromise (table 1) and made in consultation with the infant's cardiologist.
●Acyanotic heart disease and are receiving medication to control heart failure and will require cardiac surgical procedures
●Moderate to severe pulmonary hypertension
Infants with CHD who are receiving palivizumab prophylaxis and require cardiac bypass during RSV season should receive a postoperative dose of palivizumab 15 mg/kg IM as soon as they are medically stable because the mean serum palivizumab concentration has been observed to decrease by more than 50 percent after cardiac bypass [26,54,55].
The benefits of palivizumab for children with hemodynamically significant CHD were demonstrated in a multicenter randomized trial that included 1287 children younger than two years of age . Palivizumab reduced laboratory-confirmed RSV hospitalization (5.3 versus 9.7 percent; 45 percent reduction, 95% CI 23-67) and duration of hospitalization (57.4 versus 129 days per 100 children). In subgroup analysis, palivizumab reduced RSV hospitalization among children with acyanotic heart disease (5 versus 11.8 percent) and cyanotic heart disease (5.6 versus 7.9 percent), but the reduction in children with cyanotic heart disease was not statistically significant.
Subsequent observational studies suggest that the rate of RSV hospitalization for children with hemodynamically significant CHD who do not receive palivizumab is only 2 to 3 percent [56-58], which is lower than in the placebo recipients in the randomized trial (9.7 percent) . As the RSV hospitalization rate among children with hemodynamically significant CHD who do not receive palivizumab decreases, the number of patients who need to be treated to prevent one hospitalization increases, as does the cost-to-benefit ratio.
Neuromuscular disorder — Decisions regarding palivizumab prophylaxis during the first year of life for children with neuromuscular disease that impairs the ability to clear secretions from the upper airway (eg, ineffective cough) should be made on a case-by-case basis. Such children may be at risk for prolonged hospitalization related to lower respiratory tract infections. However, population-based and prospective studies defining the risk of RSV hospitalization in children with neuromuscular disease are lacking [1,26].
Pulmonary abnormalities — Decisions regarding palivizumab prophylaxis during the first year of life for children with pulmonary malformations, tracheoesophageal fistula, upper airway conditions, or conditions requiring tracheostomy should be made on a case-by-case basis. Children with these conditions may be at risk for prolonged hospitalization related to lower respiratory tract infection. However, population-based and prospective studies defining the risk of RSV hospitalization in children with pulmonary abnormalities are lacking [1,26].
Immunocompromised host — Decisions regarding palivizumab prophylaxis in immunocompromised hosts must be made on a case-by-case basis. Although palivizumab prophylaxis has not been evaluated in immunocompromised children in controlled trials, children with severe immunodeficiencies (eg, severe combined immunodeficiency or severe acquired immunodeficiency, children younger than two years of age who have undergone lung transplantation, heart transplantation, or hematopoietic stem cell transplantation) may benefit from immunoprophylaxis [1,26].
Down syndrome — Prophylactic palivizumab may be warranted for infants with Down syndrome and additional risk factors for RSV lower respiratory tract infection, including birth during the peak of RSV season.
Down syndrome, independent of prematurity or hemodynamically significant CHD, appears to be a risk factor for RSV lower respiratory tract infection and hospitalization [59-62]. In addition, children with Down syndrome who are admitted to the hospital with RSV infection appear to be at increased risk for severe RSV disease (eg, need for intensive care, longer hospital stay) [63-66].
RSV immunoprophylaxis has not been evaluated in children with Down syndrome in controlled trials. However, in a prospective registry studies, administration of palivizumab was associated with decreased risk of hospitalization among children <2 years of age with Down syndrome [67,68]. Confirmation of this finding in a randomized trial is necessary before palivizumab can be routinely recommended for children with Down syndrome.
Native American and Alaska Native infants — A lower threshold for administration of palivizumab prophylaxis may be warranted for Native American and Alaska Native infants <12 months of age because of the higher rates of RSV hospitalization and the costs associated with transport of such infants from remote locations [1,26,69-73]. In a placebo-controlled randomized trial, motavizumab (another humanized monoclonal antibody) reduced the risk of RSV hospitalization in Native American infants who were younger than six months of age and born at ≥36 weeks' gestation (2 versus 11 percent, RR 0.13, 95% CI 0.08-0.21) .
Conditions for which palivizumab is not indicated
Cystic fibrosis — We do not suggest palivizumab prophylaxis for children with cystic fibrosis (CF) unless they have other indications for palivizumab. Although RSV appears to be associated with pulmonary exacerbation in children with CF , the benefits of palivizumab have not been well studied.
A 2016 systematic review identified one randomized trial of palivizumab prophylaxis in children with CF and concluded that additional randomized trials are necessary to draw firm conclusions about the safety and efficacy of palivizumab in children with CF . In a subsequent retrospective analysis of data from the Cystic Fibrosis Foundation Patient Registry, no association was found between receipt of palivizumab during the first two years of life and improved outcomes at age seven years (eg, lung function, time to first positive Pseudomonas respiratory culture, or pulmonary-related hospitalizations) . (See "Cystic fibrosis: Overview of the treatment of lung disease", section on 'Prevention of infection'.)
The AAP guidance for palivizumab prophylaxis indicates that palivizumab may be warranted for children <12 months with CF and evidence of BPD and/or nutritional compromise and children <2 years with CF and manifestations of severe lung disease (ie, previous hospitalization for pulmonary exacerbation, abnormalities on chest radiography or chest tomography that persist when stable, or weight for length <10th percentile) .
Prevention of recurrent wheezing — Although palivizumab appears to reduce the risk of recurrent wheezing in premature infants without BPD or other underlying cardiopulmonary conditions [77-80], palivizumab prophylaxis is not recommended to reduce the risk of recurrent wheezing or asthma in premature infants without BPD .
Prevention of health care-associated RSV — For infants in whom palivizumab is not otherwise indicated, palivizumab is not recommended for the prevention of health care-associated RSV . (See 'Infection control in the health care setting' above.)
Dose and schedule
●Regimen – The dose of palivizumab is 15 mg/kg IM once per month typically for a maximum of five doses, with a maximum interval between doses of 35 days. Exceptions to the maximum of five doses may be made in areas where there was increased interseasonal activity of RSV during the coronavirus disease 2019 (COVID-19) pandemic. (See 'Increased interseasonal activity during COVID-19 pandemic' below.)
In two large observational studies, intervals of ≤35 days between doses were associated with decreased risk of hospitalization [18,81].
●Timing of first dose – The first dose is administered before the RSV season begins (usually in November in the northern hemisphere, but may vary by geographic region) . (See "Respiratory syncytial virus infection: Clinical features and diagnosis", section on 'Epidemiology'.)
Infants who qualify for palivizumab but remain hospitalized when the first dose is due may receive the first dose 48 to 72 hours before discharge home or promptly after discharge (insurance coverage may be a factor in this decision for infants in the United States) .
●Number of doses – When an infant qualifies for initiation of prophylaxis at the beginning of the RSV season and is not hospitalized for breakthrough RSV infection, all five doses should be administered, even if the infant becomes old enough that prophylaxis is no longer indicated . As an example, an infant born at <29 weeks' gestation who is without BPD and turns 12 months old in January should still receive immunoprophylaxis in February and March.
Fewer than five doses may be administered to an infant who qualifies for palivizumab and is born during the RSV season . An infant born in February typically would receive only two doses (February and March) but may receive more if the local RSV season extends into April or May. The hospital laboratory or health department may have data to help determine when the local RSV season has ended.
Although abbreviated schedules of three or four doses have been used, studies evaluating the effectiveness of abbreviated or partial schedules in preventing RSV hospitalization have conflicting results [81-83].
Increased interseasonal activity during COVID-19 pandemic — During the COVID-19 pandemic, interseasonal RSV activity has increased in some regions in the Northern and Southern hemispheres, resulting in increased hospitalizations and emergency department visits. (See "Respiratory syncytial virus infection: Clinical features and diagnosis", section on 'Epidemiology'.)
In areas with interseasonal activity that was similar to that in a typical fall-winter season, the AAP supported administration of palivizumab to eligible infants outside of the typically recommended schedule. During the 2022-2023 RSV season, the AAP supports providing more than five consecutive doses of palivizumab to eligible children who initiated palivizumab earlier than typically recommended due to increased interseasonal activity if RSV disease activity persists at high levels in a given region through the fall and winter . Information about state-level RSV activity in the United States is available from the Centers for Disease Control and Prevention . The AAP will monitor RSV activity and update this guidance if necessary. (See 'Indications for palivizumab' above and 'Dose and schedule' above.)
Breakthrough RSV infection — Immunoprophylaxis should be discontinued if the infant experiences breakthrough infection requiring hospitalization. The risk of a second RSV hospitalization during the same season is extremely low (<0.5 percent) . In addition, repeat infections generally are less severe than the initial infection.
Home administration — Administration of palivizumab in the home setting may increase adherence to the schedule [18,87-90]. In a registry study, administration in the home setting was associated with a decreased rate of RSV-associated hospitalization (0.4 versus 1.2 percent when administered in an outpatient setting) .
Adverse events — Rare cases of severe hypersensitivity reactions have been described after an initial dose, as well as after reexposure [15,91]. Among 13,025 infants enrolled in the Canadian registry of children receiving palivizumab for RSV (2008 to 2013), six patients (0.05 percent) had 14 hypersensitivity reactions (2.8 per 10,000 patient-months) . Only four other patients had serious adverse events that were possibly or probably related to palivizumab, but the events could not be classified because the records were incomplete.
In two studies evaluating the safety of palivizumab during two consecutive seasons, no serious adverse events were noted [92,93]. Only 1 of 118 children had a significant increase in antipalivizumab antibody titer, and the antibody response declined with continued dosing [92,93]. In a systematic review, escape mutants resistant to palivizumab were isolated from approximately 5 percent of children who were receiving monthly palivizumab prophylaxis and required hospitalization for breakthrough RSV infection .
NIRSEVIMAB — Nirsevimab is a monoclonal antibody that targets the prefusion conformation of the RSV F glycoprotein. It has a long half-life and potent neutralizing activity. In multicenter, placebo-controlled randomized trials in otherwise healthy infants born at ≥29 weeks gestation, a single injection of nirsevimab appears to be safe and effective in preventing RSV lower respiratory tract infection that requires medical attention (eg, emergency department or clinic visit) and RSV-associated hospitalization for 150 days [94-96].
VACCINE DEVELOPMENT — Live-attenuated vaccines are in development for infants and young children [97,98]. In pooled data from five phase 1 trials in children age 6 to 24 months, live-attenuated RSV vaccines prevented medically attended RSV acute respiratory illness (estimated efficacy 67 percent, 95% CI 24-85 percent) .
Challenges to development of an RSV vaccine for young infants include immature immunity, suppression of immune response by maternal antibody, antigenically divergent strains, and avoiding enhanced disease in recipients who subsequently become infected with wild-type virus [97,99,100].
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Bronchiolitis in infants and children".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or email these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient education" and the keyword[s] of interest.)
●Beyond the Basics topic (see "Patient education: Bronchiolitis and RSV in infants and children (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●General measures – General measures to prevent RSV infection include hand washing, practicing cough hygiene, avoidance of tobacco and other smoke, and restricting participation in childcare during RSV season for high-risk infants (if possible). (See 'General measures' above.)
●Infection control in the health care setting – Measures for the prevention of health care-associated RSV infections include handwashing and appropriate use of gloves, masks, gowns, and eye protection for health care workers, isolation of patients in private rooms or in rooms with other RSV-infected patients (cohorting patients), and cohorting heath care personnel. (See 'Infection control in the health care setting' above.)
●Palivizumab immunoprophylaxis – Palivizumab is a humanized monoclonal antibody against the RSV F glycoprotein. It prevents hospitalization in children at high risk for RSV disease with few adverse effects but may be associated with high out-of-pocket costs. (See 'Efficacy and effectiveness' above.)
For the purpose of palivizumab prophylaxis, we define bronchopulmonary dysplasia (BPD) by gestational age <32 weeks and need for supplemental oxygen for the first 28 days after birth. (See 'Prematurity with bronchopulmonary dysplasia' above.)
•For infants with BPD who are younger than one year of age at the start of RSV season or who are age 12 through 23 months and required medical therapy (eg, supplemental oxygen, glucocorticoids, diuretics) for BPD within six months of the start of RSV season, we suggest palivizumab prophylaxis rather than no prophylaxis (Grade 2A). (See 'Prematurity with bronchopulmonary dysplasia' above.)
•For infants younger than one year of age who were born at <29 weeks' (ie, ≤28 weeks, 6 days) gestation who do not have BPD, we suggest palivizumab prophylaxis rather than no prophylaxis (Grade 2B). (See 'Prematurity without bronchopulmonary dysplasia' above.)
•For infants younger than one year of age who were born between 29 and 32 weeks' gestation, the authors of this topic review individualize decisions about palivizumab by considering additional risk factors (eg, age <4 months during peak RSV season, childcare attendance, parental smoking, older siblings in the home, prevalence of RSV in the community). (See 'Prematurity without bronchopulmonary dysplasia' above.)
●Other potential target groups – Other potential target groups for palivizumab prophylaxis are listed below. Decisions for children in these groups should be made on a case-by-case basis, typically in consultation with the child's specialist (eg, cardiologist, neurologist). (See 'Other potential target groups' above.)
•Children younger than one year of age with neuromuscular disorders that impair the ability to clear secretions from the upper airways or pulmonary abnormalities (see 'Neuromuscular disorder' above and 'Pulmonary abnormalities' above)
•Children younger than two years of age who will be profoundly immunocompromised (eg, those with severe combined immunodeficiency, those younger than two years of age who have undergone lung transplantation or hematopoietic stem cell transplantation) during the RSV season (see 'Immunocompromised host' above)
•Children with Down syndrome who have additional risk factors for RSV lower respiratory tract infection (see 'Down syndrome' above)
•Native American and Alaska Native infants (see 'Native American and Alaska Native infants' above)
●Dose and schedule – Palivizumab 15 mg/kg is administered intramuscularly once per month typically for a maximum of five doses. Exceptions to the maximum of five doses may be made in areas where there was increased interseasonal activity of RSV during the COVID-19 pandemic.
The first dose is administered before the RSV season begins (usually in November for infants in the northern hemisphere). The interval between doses should not exceed 35 days. When palivizumab prophylaxis is initiated at the beginning of RSV season, all five doses should be administered. However, prophylaxis should be discontinued if the infant experiences breakthrough infection requiring hospitalization. (See 'Dose and schedule' above and 'Increased interseasonal activity during COVID-19 pandemic' above.)
●Adverse events – Serious adverse events (eg, severe hypersensitivity reaction) associated with palivizumab administration are rare. Palivizumab-resistant isolates have been recovered from approximately 5 percent of children hospitalized with breakthrough RSV infection while receiving monthly palivizumab prophylaxis. (See 'Adverse events' above.)
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