eMedicine Specialties > Pediatrics: General Medicine > Infectious Disease

Respiratory Syncytial Virus (RSV) Infection: Follow-up

Author: Leonard R Krilov, MD, Chief of Pediatric Infectious Diseases, Vice Chair, Department of Pediatrics, Professor of Pediatrics, Winthrop University Hospital
Contributor Information and Disclosures

Updated: Jul 27, 2009

Follow-up

Deterrence/Prevention

• Respiratory syncytial virus (RSV) transmission appears to occur via contact with infected secretions through hand-to-hand spread and/or fomites and respiratory droplets with an incubation period of 3-5 days.¹² Aerosolized secretions appear to be less important in RSV transmission; thus, attention to handwashing and cleaning of environmental surfaces are important to prevent RSV transmission. In the hospital setting, isolation of patients infected with RSV as a group and wearing of mask and gown during close contact with infected children are important in controlling nosocomial spread. Transmission of RSV on pediatric units has been shown to be a significant problem.
• Despite good environmental hygiene, RSV infection is likely to occur with significant frequency.
• Immunoglobulin products with high anti-RSV antibody titers have proved beneficial when given monthly for prophylaxis in select groups of high-risk infants. Presently, this is accomplished with monthly administration of palivizumab (Synagis), a humanized monoclonal antibody.¹³
  • RSV-intravenous immunoglobulin (IVIG) is a pooled polyclonal human immunoglobulin product prepared from donors with high titers of RSV antibodies. When administered to high-risk infants with prematurity and/or chronic lung disease, a significant decrease in RSV-related hospitalization was noted. Additionally, treated infants had less severe hospital courses if admitted with RSV disease, fewer other respiratory infection hospitalizations, and fewer cases of otitis media than placebo recipients. This product requires intravenous administration at a dose of 750 mg/kg monthly during RSV season (typically, November through May or April in temperate climates). Given the need for monthly intravenous infusion and fluid volume load, the number of children who can be protected in this manner was limited, and, with the licensure of palivizumab (Synagis), this agent is no longer being manufactured.
  • Presently, passive protection against RSV is achieved successfully through monthly intramuscular injection of the humanized monoclonal anti-RSV antibody palivizumab (Synagis; MedImmune; Gaithersburg, Md) at a dose of 15 mg/kg IM per month.
    • This product demonstrated a 55% reduction in RSV hospitalization in premature infants born at less than 35 weeks' gestation who were younger than 6 months chronological age and in infants who had bronchopulmonary dysplasia and were younger than 24 months chronological age;¹⁴ This reduction led to FDA approval in 1998.
    • A separate study in infants younger than 2 years who had hemodynamically significant congenital heart disease also demonstrated safety and efficacy of palivizumab prophylaxis in this high-risk population.  Subsequent postmarketing studies have continued to demonstrate efficacy. In November 2005, a stable liquid preparation of the drug became available, replacing the lyophilized form used previously. The dosing and concentration of the liquid preparation have not changed
    • Immunoglobulin products are expensive to administer (approximately $5,000-6,000 per child per year), leading to debate regarding which children should receive such prophylaxis
    • Palivizumab (Synagis) is approved for prophylaxis of children at high risk for severe RSV disease. Clinical trials have demonstrated efficacy and safety in premature infants younger than 6 months and those with chronic lung disease of infancy and congenital heart disease younger than 2 years at the start of the RSV season. Infants with immunodeficiency or severe neuromuscular disease have not been studied in conjunction with these products because of limitations in the numbers of such patients
    • The American Academy of Pediatrics (AAP) guidelines for RSV prophylaxis (see below) attempt to address these issues by grading the indications for preventive therapy by degree of prematurity and/or risk factor.¹⁵ Pending further follow-up and economic impact studies, the AAP recommendations, last revised in 2006, provide a rational approach to selecting candidates for RSV prophylaxis.
• The AAP Committee on Infectious Diseases guidelines for candidates for palivizumab (Synagis) prophylaxis are as follows:¹⁵
  • Infants younger than 24 months who have hemodynamically significant congenital heart disease (cyanotic or acyanotic lesions) or chronic lung disease and are off oxygen and/or pulmonary medications for less than 6 months at the start of RSV season
  • Premature infants born at less than 28 weeks' gestational age who are younger than 1 year chronological age at the start of RSV season
  • Premature infants born at 29-32 weeks' gestational age who are younger than 6 months chronological age at the start of RSV season
  • Infants born at 33-35 weeks' gestational age who are younger than 6 months chronological age and have at least 2 additional risk factors at the start of RSV season¹⁶
• The AAP guidelines highlight child care attendance, school-aged siblings, exposure to environmental pollutants, congenital anomalies of the airway, and severe neuromuscular disorders as the primary additional risk factors for these patients.
• Attempts to develop a vaccine against RSV (as opposed to the passive protection discussed above) have been unsuccessful to date.¹⁷ A formalin-inactivated RSV vaccine was developed in the 1960s. Although initial serological responses to this vaccine appeared promising, children who received this vaccine developed more severe disease, with a number of deaths, when exposed to natural RSV infection. The development of a successful RSV vaccine must address this issue and achieve protection of very young children if it is to have an impact on severe RSV disease. Recent progress in this area has included development of stable, live-attenuated RSV vaccines that can be administered as nasal spray. Despite progress in this area, a vaccine that is ready for use in clinical practice is still likely 5-10 years away.
• A second-generation monoclonal antibody, motavizumab, has increased affinity for RSV compared with palivizumab and is currently under investigation. Preliminary data compared palivizumab with motavizumab in a premature population suggested noninferiority for motavizumab in preventing hospitalization and superiority to palivizumab for protection against medically attended lower respiratory infection. Motavizumab is not currently FDA approved or available for clinical use.¹⁸
• Another approach is the development of an RSV vaccine that involves use of cloned RSV surface proteins as potential subunit vaccines. RSV fusion (F) and glycoprotein (G) can induce neutralizing and protective antibodies and are the components in development. These are being evaluated for potential immunization of young children and also for administration to pregnant women during the last trimester to boost anti-RSV antibody levels transferred to the infant.

Complications

• Infants hospitalized for RSV lower respiratory tract (LRT) infection in infancy have a higher risk for subsequent wheezing and abnormal pulmonary function tests as long as 10 years later than age-matched control subjects who did not have such an admission. RSV's role in causing subsequent reactive airway disease remains controversial. Several small studies have suggested that infants who are hospitalized with RSV infection and treated with ribavirin have better pulmonary function on follow-up than children who do not receive such therapy. If this finding is confirmed, it offers better understanding of the link between RSV LRT in infancy and subsequent reactive airway disease. Similarly, analyses of recipients of RSV prophylaxis compared with control subjects may help answer this clinically important question.
• A small retrospective study in Europe and Canada suggested that premature infants who received palivizumab prophylaxis had less subsequent respiratory illness visits over a 2-year period than infants matched for gestational and chronological age who did not receive prophylaxis.

Prognosis

• Children hospitalized secondary to RSV infection typically recover and are discharged in 3-4 days. High-risk infants remain hospitalized longer and have higher rates of ICU admission and mechanical ventilation. 
• Infants hospitalized due to RSV infection have higher rates of subsequent wheezing than age-matched controls not hospitalized for this condition over the next 10 or more years. Whether RSV leads to alterations of airways and/or immune responses that contribute to these subsequent events or is just a marker for abnormal airways is still not completely understood. 

Patient Education

• For excellent patient education resources, visit eMedicine's Pneumonia Center and Cold and Flu Center. Also, see eMedicine's patient education articles Viral Pneumonia and Flu in Children.

Miscellaneous

Medicolegal Pitfalls

• The primary medical/legal pitfall relating to respiratory syncytial virus (RSV) disease is failure to recognize the severity of lung disease and degree of hypoxemia in a particular child. Careful history, physical examination, and, if indicated, oxygen saturation measurement should be adequate for revealing severe illness children.
• The author is not aware of any related legal issues to date, but it has been suggested that failure to offer prophylactic therapy (eg, palivizumab) to a high-risk neonate who subsequently develops severe RSV disease might pose a medicolegal concern. Numerous law suits for high-risk infants who have acquired nosocomial RSV infection have been filed.

Special Concerns

• High-risk groups for severe RSV infection include the following:
  • Premature infants in their first year of life (the younger the child is [gestational and chronological age] at the start of RSV season, the greater the risk)
  • Infants with chronic lung disease (eg, bronchopulmonary dysplasia, cystic fibrosis) during their first 2 years of life
  • Children with hemodynamically significant congenital heart disease, especially with increased pulmonary blood flow
  • Immunodeficient states
  • Children with metabolic and neuromuscular disorders
  • Children of multiple births (triplets or greater)

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