Respiratory syncytial virus infection: Prevention in infants and children

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.

●(See "Respiratory syncytial virus infection: Clinical features and diagnosis in infants and children".)

●(See "Respiratory syncytial virus infection: Treatment in infants and children".)

●(See "Bronchiolitis in infants and children: Clinical features and diagnosis".)

●(See "Bronchiolitis in infants and children: Treatment, outcome, and prevention".)

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 premature birth, 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 in infants and children", 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 in infants and children".)

IMMUNOPROPHYLAXIS

●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. A dose of nirsevimab is expected to provide protection for at least five months such that only one dose is needed at the beginning of the RSV season. Nirsevimab was approved by the US Food and Drug Administration in 2023 for all infants and should be used in place of palivizumab, even for premature infants and those with other risk factors, unless nirsevimab is not available [15,16].

●Efficacy – In multicenter, placebo-controlled trials in otherwise healthy infants born at ≥29 weeks' gestation entering their first RSV season, a single injection of nirsevimab appeared to be safe and effective in preventing RSV lower respiratory tract infection (LRTI) that required medical attention (eg, emergency department or clinic visit) and RSV-associated hospitalization [17-19]. In one study, more than 1400 infants born between 29 and 35 weeks' gestation were randomly assigned in a 2:1 ratio to receive a dose of nirsevimab or placebo [17], and in another study, more than 1400 infants who were born ≥35 weeks' gestation were randomly assigned in the same manner [18].

In the first study, infants assigned to receive nirsevimab had fewer RSV LRTIs requiring medical attention than those receiving placebo (2.6 versus 9.5 percent, relative efficacy 70.1 percent, 95% CI 52.3- to 81.2), and the incidence of hospitalization at five months was lower (0.8 versus 4.1 percent, relative efficacy 78.4 percent, 95% CI 51.9 to 90.3) [17]. Similarly, in the second study, fewer infants receiving nirsevimab required medical attention (1.2 versus 5.0 percent, relative efficacy 74.5 percent, 95% CI 49.6 to 87.1), and they had a lower incidence of hospitalization (0.6 versus 1.6 percent, relative efficacy 62.1 percent, 95% CI -8.6 to 86.8) [18].

In another study conducted in France, Germany, and the United Kingdom, more than 8000 otherwise healthy infants ≤12 months, born at ≥29 weeks' gestation, and entering their first RSV season were assigned to receive one dose of nirsevimab or no intervention [20]. The group who received nirsevimab had fewer hospitalizations for RSV-associated LRTI (0.3 versus 1.5 percent, efficacy 83.2 percent, 95% CI 67.8-92.0) and fewer infants with an oxygen saturation <90 percent (0.1 versus 0.5 percent, efficacy 75.7 percent, 95% CI 32.8-92.9).

●Effectiveness – Early estimates of nirsevimab's real-world effectiveness are encouraging. During its first season of use in the United States, a case-control study to evaluate nirsevimab's effectiveness for prevention of RSV-associated hospitalizations was conducted at four New Vaccine Surveillance Network pediatric hospitals [21]. Among 699 infants (<8 months of age) who were hospitalized for an acute respiratory illness, 407 (58 percent) tested positive for RSV. Of these, only 6 (1.5 percent) had received nirsevimab upon entering the RSV season or at birth during RSV season. Among the 292 (42 percent) infants who tested negative for RSV, 53 (18 percent) had received nirsevimab (adjusted odds ratio 0.10, 95% CI 0.04-0.25).

We agree with the recommendations of the Centers for Disease Control and Prevention's (CDC) and the American Academy of Pediatrics' (AAP) for administering nirsevimab, and these are reflected in the following sections (algorithm 1 and algorithm 2 and table 1) [15,22,23].

First RSV season

Infants <8 months

Birthing parent did not receive RSV vaccination during pregnancy — We recommend that all infants younger than eight months who are born during the RSV season or are entering their first RSV season receive one dose of nirsevimab if the birthing parent did not receive RSV vaccination during pregnancy or the vaccination status of the birthing parent is unknown (algorithm 1). Details regarding the dose and administration of nirsevimab are presented below. (See 'Administration' below.)

If nirsevimab is not received on time, it should be administered at any time during the RSV season unless the infant has reached eight months of age.

Birthing parent did receive RSV vaccine during pregnancy

●Vaccination occurred <14 days before delivery – We recommend that all infants who are born during the RSV season or are entering their first RSV season receive one dose of nirsevimab if their birthing parent was vaccinated within 14 days of delivery (algorithm 1).

●Vaccination occurred ≥14 days before delivery – We do not recommend immunoprophylaxis for infants whose birthing parent was vaccinated more than 14 days before delivery (algorithm 1).

However, if any of the following exceptions apply, nirsevimab may be given if the provider judges that the incremental benefit to the infant is warranted: the birthing parent has a condition that may prevent an adequate immune response or is associated with reduced transplacental antibody transfer (eg, persons with immunocompromising conditions); the infant requires cardiopulmonary bypass or extracorporeal membrane oxygenation; or the infant is at substantial increased risk for severe RSV disease (eg, hemodynamically significant heart disease, intensive care admission, oxygen requirement at discharge).

Details regarding the timing and dose of nirsevimab are presented below. (See 'Administration' below.)

Infants ≥8 months

●Healthy infants ≥8 months old who did not receive a dose of nirsevimab on time are not eligible for a catch-up dose (algorithm 1).

●Infants at increased risk for severe disease that did not receive nirsevimab before eight months of age should receive one dose of nirsevimab. Criteria for increased risk are listed in the table (table 1). Details regarding the timing and dose of nirsevimab are presented below (algorithm 1). (See 'Administration' below.)

Second RSV season

All infants <8 months — All infants who did not receive nirsevimab during their first RSV season and are younger than eight months entering their second RSV season should receive a dose of nirsevimab. On the other hand, healthy infants who received nirsevimab during their first RSV season should not receive another dose, even if they are less than eight months of age (algorithm 2).

Details regarding the timing and dose of nirsevimab are presented below. (See 'Administration' below.)

Infants 8 through 19 months at increased risk for severe disease — We suggest that infants and children who are 8 through 19 months old and at increased risk for severe RSV receive a second dose of nirsevimab upon entry into their second RSV season (algorithm 2 and table 1). This advice also applies to infants who received palivizumab during their first RSV season.

Criteria for increased risk of severe disease include [15]:

●Children with bronchopulmonary dysplasia (BPD; also known as chronic lung disease of prematurity) who required medical support (eg, chronic corticosteroid therapy, diuretic therapy, or supplemental oxygen) any time during the six-month period before the start of the RSV season

●Children who are severely immunocompromised

●Children with cystic fibrosis who have manifestations of severe lung disease (previous hospitalization for pulmonary exacerbation in the first year of life or abnormalities on chest imaging that persist when stable) or have weight-for-length <10^th percentile

●American Indian and Alaska Native children

For the purpose of nirsevimab prophylaxis, we use the definition for BPD provided in the AAP guidelines: gestational age <32 weeks and a requirement for supplemental oxygen for the first 28 days after birth [24]. (See "Bronchopulmonary dysplasia (BPD): Clinical features and diagnosis", section on 'Definitions and severity of BPD'.)

Details regarding the timing and dose of nirsevimab are presented below. (See 'Administration' below.)

Administration

Timing — RSV season in most of the continental United States generally runs from October to the end of March. Because this varies geographically, health care providers should adjust the timing of immunoprophylaxis if indicated by their community's RSV activity.

●Infants born during RSV season – Nirsevimab should be administered within the first week of life. If the infant's hospitalization after birth is extended due to prematurity or other problems, the nirsevimab should be administered shortly before or promptly after hospital discharge.

●Infants born before RSV season – Nirsevimab should be administered shortly before the season begins. Eligible infants who do not receive nirsevimab before the RSV season begins may receive it at any time before the season ends. For healthy infants, eligibility requires that they be <8 months old at the time of administration.

●Children with increased risk for severe disease entering their second RSV season – All children ≤19 months with increased risk should receive a second dose of nirsevimab just before the start of the RSV season. (See 'Infants 8 through 19 months at increased risk for severe disease' above.)

Dose — The dose of nirsevimab is based on weight and age.

●Infant's first RSV season

•Weight <5 kg – One 50 mg intramuscular (IM) dose

•Weight ≥5 kg – One 100 mg IM dose

●Child's second RSV season

•One 200 mg IM dose

When age-appropriate vaccines are indicated, simultaneous administration of nirsevimab with the vaccines is recommended.

Adverse events — Adverse events reported in the two multicenter trials of healthy infants ≥29 weeks gestation were similar between the nirsevimab groups and the placebo groups, including serious adverse events [17,18]. Additionally, there were no anaphylactic reactions. Five deaths (0.3 percent) occurred in the nirsevimab groups and three (0.3 percent) occurred in the placebo groups. None of the deaths were judged by the investigators to be related to nirsevimab or placebo.

Postmarketing, serious hypersensitivity reactions have been reported [25]. These include urticaria, dyspnea, cyanosis, and hypotonia.

Nirsevimab not available — Prior to the development of nirsevimab, palivizumab was the only monoclonal antibody available for the prevention of serious RSV LRTI in children at high risk. Palivizumab targets both the prefusion and postfusion conformation of the RSV F glycoprotein and has lower neutralizing activity than nirsevimab. When nirsevimab is not available, we suggest that palivizumab be used for infants that were previously designated by the AAP as high risk for severe RSV disease.

Palivizumab is administered as five monthly IM injections during the RSV season. If nirsevimab becomes available and <5 doses of palivizumab have been administered, the infant should receive one dose of nirsevimab and no additional doses of palivizumab. Infants who have received nirsevimab should not receive palivizumab during the same RSV season.

●Palivizumab eligibility – Our suggested criteria for palivizumab prophylaxis are generally consistent with those of the AAP, which were reaffirmed in 2019 (table 2) [24,26]. However, recommendations for and availability of palivizumab prophylaxis vary geographically. (See 'Society guideline links' below.)

•Prematurity with BPD – The terminology for and definition of BPD (also known as neonatal chronic lung disease and chronic lung disease of prematurity) have changed over time. For the purpose of palivizumab prophylaxis, we use the definition for BPD provided in the AAP guidelines: gestational age <32 weeks, 0 days and a requirement for supplementation oxygen for the first 28 days after birth [24]. (See "Bronchopulmonary dysplasia (BPD): Clinical features and diagnosis", section on 'Definitions and severity of BPD'.)

We suggest palivizumab prophylaxis for infants with BPD who have either of the following (table 2) [24,27]:

-Age <1 year at the start of RSV season.

-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.

•Prematurity without BPD – Suggestions for palivizumab prophylaxis among premature infants without BPD depend upon the degree of prematurity (table 2) [24]:

-We suggest that palivizumab be administered to preterm infants without BPD who were born at <29 weeks' 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 make decisions on a case-by-case basis after discussing the potential benefits and costs with the infant's caregiver(s). Recommendations from professional societies regarding palivizumab prophylaxis in preterm infants without BPD in this gestational age range are inconsistent [24,28]. (See 'Society guideline links' below.)

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 [3,28-30]. (See "Respiratory syncytial virus infection: Clinical features and diagnosis in infants and children", section on 'Risk factors'.)

•Congenital heart disease – Decisions regarding palivizumab prophylaxis for children with congenital heart disease (CHD) should be individualized according to the degree of cardiovascular compromise (table 2) and made in consultation with the infant's cardiologist.

Palivizumab prophylaxis is more likely to be beneficial for infants <12 months of age with either of the following [1]:

-Acyanotic heart disease 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 the 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 [24,31,32].

•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 2). Children in the first two target groups below may be at risk for prolonged hospitalization related to LRTIs. However, population-based and prospective studies defining the risk of RSV hospitalization in these children are lacking [1,24].

-Neuromuscular disorder – Children with neuromuscular disease that impairs the ability to clear secretions from the upper airway (eg, ineffective cough) should be considered for palivizumab prophylaxis during their first year of life.

-Pulmonary abnormalities – Children with pulmonary malformations, tracheoesophageal fistula, upper airway conditions, or conditions requiring tracheostomy should be considered for palivizumab prophylaxis during their first year of life.

-Immunocompromised host – 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 cell transplantation) may benefit from palivizumab prophylaxis [1,24].

-Down syndrome – Prophylactic palivizumab may be warranted for infants younger than 12 months of age with Down syndrome and additional risk factors for RSV LRTI, 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 LRTI and hospitalization [33-36]. 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) [37-40].

-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 challenges associated with transport of such infants from remote locations [1,24,41-45].

●Palivizumab 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 of 35 days between doses.

•Timing of first dose – The first dose is administered before the RSV season begins [24]. (See "Respiratory syncytial virus infection: Clinical features and diagnosis in infants and children", 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) [24].

•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 [24]. 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 toward the end of the RSV season [24]. For example, 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 [46-48].

Palivizumab does not interfere with routine childhood immunizations, including live viral vaccines (eg, measle, mumps, rubella vaccine; varicella vaccine).

●Home administration – Administration of palivizumab in the home setting may increase adherence to the schedule [49-53]. 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) [52].

●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 low (<0.5 percent) [54]. In addition, repeat infections generally are less severe than the initial infection.

●Adverse events – Rare cases of severe hypersensitivity reactions have been described after an initial dose, as well as after reexposure [55,56].

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 5^th to 6^th 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 10^th to 12^th 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 health care personnel. (See 'Infection control in the health care setting' above.)

●Immunoprophylaxis – 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. A dose of nirsevimab is expected to provide protection for at least five months such that only one dose is needed at the beginning of the RSV season. Nirsevimab should be used in place of palivizumab unless nirsevimab is not available (algorithm 1 and algorithm 2 and table 1). (See 'Immunoprophylaxis' above.)

•For all infants younger than eight months who are born during the RSV season or are entering their first RSV season, we recommend one dose of nirsevimab prophylaxis rather than no prophylaxis (Grade 1B), unless the birthing parent received RSV vaccination at least 14 days prior to birth. (See 'Infants <8 months' above.)

•Healthy infants less than eight months old should only receive a dose of nirsevimab upon entering their second RSV season if they did not receive nirsevimab during their first RSV season. (See 'All infants <8 months' above.)

•For infants and children who are 8 through 19 months of age with increased risk for severe RSV, we suggest a second dose of nirsevimab upon entry into their second RSV season (Grade 2C). (See 'Infants 8 through 19 months at increased risk for severe disease' above.)

•Limited supplies of nirsevimab may require prioritization of available supply.

•If nirsevimab is not available, palivizumab should be provided to patients for whom it has been previously recommended (table 2). (See 'Nirsevimab not available' above.)

●Nirsevimab dose and schedule

•Infant's first RSV season

-Weight <5 kg – One 50 mg intramuscular (IM) dose

-Weight ≥5 kg – One 100 mg IM dose

•Child's second RSV season

-One 200 mg IM dose

Nirsevimab is administered shortly before the RSV season begins (infants younger than 8 months and those 8 through 19 months at increased risk for severe RSV disease) or within one week of birth for a newborn infant delivered shortly before or during the RSV season.

●Nirsevimab not available (palivizumab prophylaxis) – Palivizumab, another monoclonal antibody that targets both the prefusion and postfusion conformation of the RSV F glycoprotein, was the only available immunoprophylaxis for severe RSV disease prior to the development of nirsevimab. Unlike nirsevimab, palivizumab requires monthly IM injections throughout the RSV season.

The eligibility criteria for palivizumab differ from those of nirsevimab and are outlined in the table (table 2). (See 'Nirsevimab not available' above.)

•Palivizumab dose and schedule

-15 mg/kg IM once per month (maximum of five doses)

-First dose administered shortly after birth or just before RSV season begins

-Interval between doses should not exceed 35 days

-Prophylaxis should be discontinued if infant hospitalized for breakthrough RSV infection