RSV INFECTION

TesRespiratory syncytial virus infection: Prevention in infants and children

TopicGraphics (4)

Authors:

Frederick E Barr, MD, MBA

Barney S Graham, MD, PhD

Section Editor:

Morven S Edwards, MD

Deputy Editor:

Diane Blake, MD

Contributor Disclosures

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Nov 2024.

This topic last updated: Aug 26, 2024.

What's New

Real world effectiveness of nirsevimab (July 2024)

During the 2023-24 respiratory syncytial virus (RSV) season, infants could receive the monoclonal antibody nirsevimab for the first time to protect against RSV-related hospitalization. In a multicenter, case-control study conducted in France, the proportion of infants <12 months of age who had received nirsevimab and were hospitalized for RSV bronchiolitis was compared with the proportion of matched control infants who were evaluated in the emergency department for nonrespiratory illnesses [1]. Among the 690 hospitalized infants, only 60 (9 percent) had received nirsevimab compared with 97 (28 percent) of the 345 matched control infants evaluated in the emergency department (adjusted odds ratio 0.17). These data provide further evidence of the effectiveness of nirsevimab for prevention of RSV in infants who requires hospitalization. (See "Respiratory syncytial virus infection: Prevention in infants and children", section on 'Immunoprophylaxis'.)

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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 [21-23]. 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 [22]. 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).

Another multi-center case-control study was conducted in France during the first season of nirsevimab use [21]. Among 690 infants <12 months of age hospitalized for RSV bronchiolitis, only 60 (9 percent) had received nirsevimab. Among 345 matched control infants that were evaluated in the emergency department for nonrespiratory illnesses, 97 (28 percent) had received nirsevimab (adjusted odds ratio [aOR] 0.17, 95% CI 0.11-0.27).

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) [15,24,25].

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 <10th 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 [26]. (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.t