Overview

Definition:
-Respiratory Syncytial Virus (RSV) is a common respiratory virus that usually causes mild, cold-like symptoms
-However, it can be serious, especially for infants and older adults
-RSV prophylaxis refers to the use of monoclonal antibodies to prevent severe RSV disease in high-risk infants
-Nirsevimab is a long-acting monoclonal antibody, while palivizumab is an older, shorter-acting monoclonal antibody.
Epidemiology:
-RSV is the leading cause of lower respiratory tract infections (LRTIs) in infants worldwide, with an estimated 33 million cases globally each year
-In India, RSV is a significant cause of infant hospitalization and mortality
-Peak incidence occurs during the fall, winter, and spring months
-Infants born prematurely, with congenital heart disease (CHD), chronic lung disease of prematurity (CLDP), or certain neuromuscular disorders are at highest risk for severe RSV disease.
Clinical Significance:
-Severe RSV infection can lead to bronchiolitis and pneumonia, requiring hospitalization and potentially mechanical ventilation
-The burden of RSV on healthcare systems is substantial
-Effective prophylaxis can significantly reduce hospitalizations, intensive care unit (ICU) admissions, and mortality in vulnerable infant populations, thereby improving outcomes and reducing healthcare costs
-Understanding the eligibility and optimal timing of prophylaxis is crucial for pediatricians managing these at-risk infants.

Eligibility Criteria

Nirsevimab Eligibility:
-Nirsevimab is recommended for all infants born during or entering their first RSV season, regardless of prematurity status or other risk factors
-It is also recommended for children up to 24 months of age who remain vulnerable to severe RSV disease through their second RSV season.
Palivizumab Eligibility:
-Palivizumab is recommended for infants born < 29 weeks gestation, infants with significant hemodynamically significant CHD, infants with CLDP of prematurity (born < 32 weeks gestation and requiring treatment up to 12 months of age), and infants with certain severe immunocompromise or neuromuscular disorders
-Eligibility for palivizumab is typically limited to the first RSV season.
Age And Gestational Age:
-Nirsevimab is indicated for all infants from birth up to 24 months of age who are susceptible to RSV during the RSV season
-Palivizumab is primarily for infants younger than 2 years who have specific risk factors and are born prematurely or have certain chronic conditions.
High Risk Conditions: Conditions that confer high risk for severe RSV include prematurity (<35 weeks gestation, especially if with CLDP), hemodynamically significant CHD, significant CLDP of prematurity (requiring medical support), severe immunodeficiency, and certain neuromuscular disorders affecting airway clearance.

Timing Of Administration

Nirsevimab Timing:
-Nirsevimab is administered as a single intramuscular injection
-For infants born during the RSV season, it should be given shortly before the season begins or at birth if RSV season is already underway
-For infants born outside the RSV season, it should be administered at birth or before hospital discharge if RSV season is approaching
-It can be given anytime during the RSV season.
Palivizumab Timing:
-Palivizumab is administered as a series of monthly intramuscular injections throughout the RSV season
-The first dose should be given prior to the start of the RSV season
-Subsequent doses are given every month for the duration of the season (typically 5 months)
-If a child leaves a high-risk environment and returns, monthly dosing should resume.
Seasonal Considerations:
-RSV season typically spans from late fall to early spring in temperate climates
-The exact timing can vary geographically and year to year
-Prophylaxis should be initiated before the expected onset of increased RSV circulation in the community and continued throughout the season.
Administration Route: Both nirsevimab and palivizumab are administered via intramuscular injection, typically in the anterolateral thigh.

Mechanism Of Action And Efficacy

Mechanism Of Action:
-Nirsevimab and palivizumab are humanized monoclonal antibodies that bind to the fusion (F) protein of RSV, preventing the virus from entering host cells and replicating
-This passive immunity offers protection against RSV infection.
Efficacy Nirsevimab: Clinical trials have demonstrated that nirsevimab significantly reduces the incidence of medically attended RSV-associated lower respiratory tract infections by approximately 79% and RSV-related hospitalizations by approximately 83% in a broad infant population.
Efficacy Palivizumab:
-Palivizumab has been shown to reduce the risk of hospitalization due to RSV by about 55% in high-risk infants, and ICU admission by about 75%
-Its efficacy is more pronounced in infants with lower gestational ages and fewer comorbidities.
Duration Of Protection:
-Nirsevimab provides protection for the entire RSV season due to its long half-life
-Palivizumab provides protection for approximately one month per dose, necessitating monthly injections throughout the RSV season.

Adverse Events And Contraindications

Common Adverse Events: The most common adverse events reported for both nirsevimab and palivizumab are generally mild and transient, including injection site reactions (pain, redness, swelling), fever, rash, and upper respiratory infections.
Serious Adverse Events:
-Serious adverse events are rare
-Anaphylaxis has been reported with palivizumab, necessitating cautious administration and monitoring
-Thrombocytopenia has also been rarely reported.
Contraindications:
-Hypersensitivity to the active ingredient or any component of the formulation
-History of severe allergic reaction to palivizumab or nirsevimab, respectively.
Precautions:
-Caution is advised in infants with a history of anaphylaxis or other severe allergic reactions
-Close monitoring for signs of hypersensitivity reactions is recommended after administration.

Key Points

Exam Focus:
-DNB/NEET SS will test knowledge of current guidelines for RSV prophylaxis, differentiating between nirsevimab and palivizumab, their respective eligibility criteria, and optimal administration timing
-Focus on high-risk populations and seasonal considerations.
Clinical Pearls:
-Always confirm the local RSV season start and end dates
-For nirsevimab, a single dose is sufficient for a season
-For palivizumab, ensure monthly administration is maintained throughout the season for optimal efficacy
-Educate parents thoroughly on the benefits and administration schedule.
Common Mistakes: Mistakes include administering prophylaxis outside the RSV season, missing monthly doses of palivizumab, misinterpreting eligibility criteria for high-risk infants, and failing to consider nirsevimab for all infants entering their first RSV season.