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Respiratory Syncytial Virus Infection

  • Author: Leonard R Krilov, MD; Chief Editor: Russell W Steele, MD  more...
 
Updated: Jun 25, 2015
 

Practice Essentials

Respiratory syncytial virus (RSV) (see the image below) is the leading cause of lower respiratory tract infections (LRTIs) in infants and young children. Each year, 4-5 million children younger than 4 years acquire an RSV infection, and more than 125,000 are hospitalized annually in the United States because of this infection.

Electron micrograph of respiratory syncytial virus Electron micrograph of respiratory syncytial virus (RSV). RSV is most common cause of bronchiolitis and pneumonia in children younger than 1 year. Image courtesy of Centers for Disease Control and Prevention.

Essential update: Updated guidelines for palivizumab RSV prophylaxis released

The American Academy of Pediatrics has released updated guidelines addressing palivizumab prophylaxis for respiratory syncytial virus (RSV).[1]

According to the updated recommendations, palivizumab prophylaxis for RSV should be limited to infants born before 29 weeks' gestation and to infants with chronic illness such as congenital heart disease or chronic lung disease. Other recommendations include the following:

  • Give infants who qualify for prophylaxis in the first year of life no more than five monthly doses of palivizumab (15 mg/kg per dose) during the RSV season
  • In the second year of life, palivizumab prophylaxis is recommended only for children who needed supplemental oxygen for 28 days or more after birth and who continue to need medical intervention (supplemental oxygen, chronic corticosteroid, or diuretic therapy).
  • Clinicians may consider prophylaxis for children younger than 24 months if they will be profoundly immunocompromised during the RSV season.

Signs and symptoms

Patients with RSV infection may present with the following symptoms:

  • Fever (typically low-grade)
  • Cough
  • Tachypnea
  • Cyanosis
  • Retractions
  • Wheezing
  • Rales
  • Sepsislike presentation or apneic episodes (in very young infants)

Physical examination of the infant with RSV-related LRTI may reveal the following:

  • Evidence of diffuse small airway disease
  • Associated otitis media (viral, bacterial, or both)
  • Dehydration (assessed by evaluating skin turgor, capillary refill, and mucous membranes)

RSV LRTI in infancy may be linked with subsequent reactive airway disease, although this association remains controversial.

See Presentation for more detail.

Diagnosis

Laboratory studies generally are not indicated in the infant with bronchiolitis who is comfortable in room air, well hydrated, and feeding adequately. When warranted, nonspecific laboratory studies may include the following:

  • Complete blood count (CBC)
  • Serum electrolyte concentrations
  • Urinalysis
  • Oxygen saturation

Specific tests for RSV may be indicated for therapeutic decision making, isolation of patients, and educating parents and staff. Specific diagnostic tests for confirming RSV infection include the following:

  • Culture
  • Antigen-revealing techniques
  • Polymerase chain reaction (PCR) assay
  • Molecular probes

Chest radiography is frequently obtained in children with severe RSV infection, but for the most part, typical findings are neither specific to RSV infection nor predictive of the course or outcome.

See Workup for more detail.

Management

Supportive care is the mainstay of therapy for RSV infection. Although corticosteroids are sometimes given, the available clinical data do not support their use in the treatment of typical RSV bronchiolitis.

Pharmacologic therapies for RSV infection include the following:

  • Bronchodilators – These benefit at least a subset of patients with RSV-related LRTI
  • Alpha agonists – These have been used during acute bronchiolitis episodes, though their efficacy has not been established
  • Ribavirin – This agent is primarily reserved for patients with significant underlying risk factors and severe acute RSV disease (eg, transplant recipients)

The following agents have been used in passive immunization to protect against RSV infection:

  • RSV immune globulin intravenous (RSV-IGIV; no longer being manufactured)
  • Palivizumab (FDA-approved for prophylaxis in children at high risk for severe RSV disease)

According to American Academy of Pediatrics (AAP) guidelines for RSV prophylaxis, the following are candidates for palivizumab prophylaxis:

  • Infants younger than 24 months who have hemodynamically significant congenital heart disease (cyanotic or acyanotic lesions) or who have chronic lung disease and are off oxygen or pulmonary medications for less than 6 months at the start of the RSV season
  • Premature infants born at 28 weeks’ gestational age or less who are younger than 1 year chronological age at the start of the RSV season; once treatment is initiated, it should continue throughout the season and not stop at age 1 year
  • Premature infants born at 29-32 weeks’ gestational age who are younger than 6 months' chronological age at the start of the RSV season; once treatment is initiated, it should continue throughout the season and not stop at age 6 months
  • Infants born at 32-35 weeks’ gestational age who are younger than 3 months’ chronological age at the start of or during the RSV season and who either attend child care or have one or more siblings or other children younger than 5 years living permanently in the same household; prophylaxis should be provided only until age 3 months

Other measures proposed for preventive purposes include the following:

  • Vaccination (unsuccessful to date)
  • Vitamin D supplementation (supplementation during pregnancy may ameliorate RSV LRTI during infancy)

See Treatment and Medication for more detail.

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Background

Infection with respiratory syncytial virus (RSV; see the image below), which manifests primarily as bronchiolitis or viral pneumonia,[2] is the leading cause of lower respiratory tract infections (LRTIs) in infants and young children.

Electron micrograph of respiratory syncytial virus Electron micrograph of respiratory syncytial virus (RSV). RSV is most common cause of bronchiolitis and pneumonia in children younger than 1 year. Image courtesy of Centers for Disease Control and Prevention.

The clinical entity of bronchiolitis was described at least 100 years ago. In 1956, Morris and colleagues initially isolated RSV from chimpanzees with upper respiratory tract infections (URTIs) and identified the virus as the causative agent of most epidemic bronchiolitis cases. Subsequently, RSV has been associated with bronchiolitis and LRTI in infants. Multiple epidemiologic studies have confirmed the role of this virus as the leading cause of LRTI in infants and young children.

The peak incidence of severe RSV disease is at age 2-8 months. Overall, 4-5 million children younger than 4 years acquire an RSV infection each year, and more than 125,000 are hospitalized annually in the United States because of this infection. Virtually all children have had at least 1 RSV infection by the age of 3 years. In view of the prevalence and potential severity of this condition, it is not surprising that the World Health Organization (WHO) has targeted RSV for vaccine development.

This article reviews aspects of the virology, epidemiology, clinical course, diagnosis, treatment, and prevention of RSV-related illness.

For patient education resources, see the Cold and Flu Center, as well as Viral Pneumonia and Flu in Children.

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Pathophysiology

RSV infection is limited to the respiratory tract. Initial infection in young infants or children frequently involves the lower respiratory tract and most often manifests as the clinical entity of bronchiolitis. Inoculation of the virus occurs in respiratory epithelial cells of the upper respiratory tract. Spread of the virus down the respiratory tract occurs through cell-to-cell transfer of the virus along intracytoplasmic bridges (syncytia) from the upper to the lower respiratory tract.

The illness may begin with upper respiratory symptoms and progress rapidly over 1-2 days to the development of diffuse small airway disease characterized by cough, coryza, wheezing and rales, low-grade fever (< 101°F), and decreased oral intake. A family history of asthma or atopy is frequently obtained.[3, 4] In more advanced disease, retractions and cyanosis may be noted, and as many as 20% of patients may develop higher temperatures.

The incidence of concomitant or secondary serious bacterial infection in association with RSV infection appears to be quite low (< 1%), with the exception of otitis media, which may occur in as many as 40% of cases. In very young infants, apnea out of proportion to respiratory signs and symptoms may be present, and in infants younger than 6 weeks, a relatively nonspecific sepsislike picture has been described.[5]

Reinfection with RSV occurs at all ages; however, with recurrent infection and increasing age, RSV infections are more likely to be limited to the upper respiratory tract. RSV URTI is more severe than the common cold, as evidenced by the 7- to 10-day duration of illness and by the finding from one study of adults with RSV that the mean absence from work is 6 days. Studies have also demonstrated severe RSV disease in elderly persons.[6]

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Etiology

In the community setting, a number of factors have been associated with an increased risk of acquiring RSV disease, including the following:

  • Childcare attendance
  • Older siblings in preschool or school
  • Crowding and lower socioeconomic status
  • Exposure to environmental pollutants (eg, cigarette smoke)
  • Multiple birth sets (especially triplets or greater)
  • Minimal breastfeeding

In infants with RSV infection, the following factors have been correlated with more severe disease and the need for hospitalization.

  • Prematurity, especially birth at less than 35 weeks’ gestation [7]
  • Age younger than 3 months at the time of infection
  • Chronic lung disease
  • Congenital heart disease
  • Congenital immunodeficiency (eg, severe combined immunodeficiency [SCID])
  • Severe neuromuscular disease
  • Toxic appearance at time of presentation
  • Respiratory rate higher than 70 breaths/min on room air
  • Atelectasis or pneumonitis on chest radiography
  • Oxygen saturation lower than 95% on room air

Although infants in these groups are at higher risk for severe RSV disease than are normal full-term infants in terms of percentages, many more children in the normal full-term group are admitted to the hospital; thus, most admissions for RSV disease occur in otherwise normal infants. A family history of asthma and genetic factors are also correlated with more severe RSV disease, though the exact relations and mechanisms have not been elucidated.

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Epidemiology

RSV LRT infection develops annually in 4-5 million children, and more than 125,000 children are admitted per year for RSV-related illness. Seasonal variations in incidence are observed (see the image below). Reinfection occurs throughout life, with the disease generally limited to the upper respiratory tract in persons older than 3 years. Severe RSV disease has been reported in older children and adults with SCID (eg, bone marrow transplantation), and RSV disease of the lower respiratory tract has been reported in elderly persons.

Respiratory syncytial virus infection season, Unit Respiratory syncytial virus infection season, United States, by region and Florida. Image courtesy of Centers for Disease Control and Prevention.

Worldwide, RSV infection is prevalent, with clinical manifestations and early occurrence of RSV LRTI comparable to those seen in the United States.

Severe RSV disease is primarily a disease of young infants and children, with a peak occurrence at the age of 2-8 months. Reinfection with RSV occurs throughout life, with disease becoming increasingly limited to the upper respiratory tract with advancing age. URT, as discussed above. Although boys and girls are equally affected by milder RSV disease, males are approximately twice as likely to be hospitalized for RSV disease. All races appear to be susceptible to RSV, showing similar disease patterns.

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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 admission to the intensive care unit (ICU) and of mechanical ventilation.

Even in children hospitalized with RSV infection, mortality is less than 1%, and fewer than 500 deaths per year are attributed to RSV in the United States. However, in select groups of high-risk patients, appreciable mortality and increased morbidity still may result from this infection.[8, 9, 10]

Infants with chronic lung disease of infancy (ie, bronchopulmonary dysplasia), congenital heart disease, or marked prematurity when hospitalized for this disease may have a 3-5% mortality rate. Additionally, such infants and patients with immunodeficient states have been shown to spend, on average, twice as long in the hospital as other patients with RSV infection (7-8 days vs 3-4 days in normal full-term infants).

Additionally, children hospitalized for RSV disease during infancy have higher rates of subsequent wheezing than age-matched controls not hospitalized for this condition over the next 10 or more years. Whether RSV itself leads to alterations of airways or immune responses contributing to these subsequent events or is just a marker for children at risk for reactive airway disease remains incompletely understood.

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Contributor Information and Disclosures
Author

Leonard R Krilov, MD Chief of Pediatric Infectious Diseases and International Adoption, Vice Chair, Department of Pediatrics, Winthrop University Hospital; Professor of Pediatrics, Stony Brook University School of Medicine

Leonard R Krilov, MD is a member of the following medical societies: American Academy of Pediatrics, American Pediatric Society, Infectious Diseases Society of America, Pediatric Infectious Diseases Society, Society for Pediatric Research

Disclosure: Nothing to disclose.

Chief Editor

Russell W Steele, MD Clinical Professor, Tulane University School of Medicine; Staff Physician, Ochsner Clinic Foundation

Russell W Steele, MD is a member of the following medical societies: American Academy of Pediatrics, American Association of Immunologists, American Pediatric Society, American Society for Microbiology, Infectious Diseases Society of America, Louisiana State Medical Society, Pediatric Infectious Diseases Society, Society for Pediatric Research, Southern Medical Association

Disclosure: Nothing to disclose.

Acknowledgements

Ashir Kumar, MD, MB Professor Emeritus, Department of Pediatrics and Human Development, Michigan State University College of Human Medicine

Ashir Kumar, MD, MB is a member of the following medical societies: American Association of Physicians of Indian Origin and Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Larry I Lutwick, MD Professor of Medicine, State University of New York Downstate Medical School; Director, Infectious Diseases, Veterans Affairs New York Harbor Health Care System, Brooklyn Campus

Larry I Lutwick, MD is a member of the following medical societies: American College of Physicians and Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

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Respiratory syncytial virus infection season, United States, by region and Florida. Image courtesy of Centers for Disease Control and Prevention.
Electron micrograph of respiratory syncytial virus (RSV). RSV is most common cause of bronchiolitis and pneumonia in children younger than 1 year. Image courtesy of Centers for Disease Control and Prevention.
 
 
 
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