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Respiratory Syncytial Virus Infection
Elizabeth C. McKeen, MD
image BASICS
Respiratory syncytial virus (RSV) is a medium-sized, membrane-bound ribonucleic acid (RNA) virus that causes acute respiratory tract illness in all ages, with the most clinically significant disease occurring in infants and young children.
DESCRIPTION
A major cause of respiratory illness, either of the upper respiratory tract (URT) or of the lower respiratory tract (LRT/bronchiolitis)
  • In adults, RSV causes URT infections (URTIs).
  • In infants and children, RSV causes URTIs and LRT infections (bronchiolitis and pneumonia).
Pediatric Considerations
  • 90-95% of children are infected at least once by the age of 24 months; reinfection is common.
  • Leading cause of pediatric bronchiolitis (50-90%)
  • Premature infants are at increased risk for severe acute RSV infection.
EPIDEMIOLOGY
  • Seasonality: Highest incidence of RSV in the United States occurs between December and March.
  • Morbidity: RSV infection leads to over 100,000 annual hospitalizations.
  • Mortality: Deaths associated with RSV are uncommon. Children with complex chronic conditions account for the majority of deaths, and the relative contribution of RSV infection to their deaths is unclear (1)[B].
ETIOLOGY AND PATHOPHYSIOLOGY
  • RSV-induced bronchiolitis causes acute inflammation, edema, and necrosis of small airway epithelium, air trapping, bronchospasm, and increased mucus production.
  • RSV develops in the cytoplasm of infected cells and matures by budding from the plasma membrane.
  • Infection spreads through droplets, either airborne or personal contact, that inoculate the nose of a susceptible individual
Genetics
  • A genetic predisposition to severe RSV infections may be associated with polymorphisms in cytokineand chemokine-related genes, including CCR5, IL4, and affiliated receptors, IL8, IL10, and IL13.
  • Infants with transplacentally acquired antibody against RSV are not protected against infection but may have milder symptoms.
RISK FACTORS
  • Risk factors for severe disease
    • Prematurity
    • Age <12 weeks
    • Underlying cardiopulmonary disease
    • Immunodeficiency
  • Other risk factors
    • Low socioeconomic status
    • Exposure to environmental air pollutants
    • Child care attendance
    • Severe neuromuscular disease
    • Adults: occupational exposure to young children, hospital staff, teachers, and daycare workers
GENERAL PREVENTION
  • Hand hygiene is the most important step to prevent the spread of RSV.
    • Alcohol-based rubs are preferred; an alternative is hand washing with soap and water (2)[B].
  • Avoid exposure to passive tobacco smoke, especially in infants and children (3)[A].
  • Isolate patients with proven or suspected RSV.
  • Palivizumab (Synagis), a monoclonal antibody directed against the fushion (F) protein of RSV, is indicated as prophylaxis for:
    • Infants and children <24 months of age with
      • Chronic lung disease of prematurity requiring medical therapy within 6 months of the start of RSV season
      • Hemodynamically significant congenital heart disease
      • Congenital abnormalities of the airway or neuromuscular disease that compromises handling airway secretions
    • Infants born at ≤28 weeks’ gestation if they are <12 months of age at the start of the RSV season; prophylaxis should be maintained through the end of the RSV season.
    • Infants born at 29 to 32 weeks’ gestation if they are <6 months of age at the start of the RSV season; prophylaxis should be maintained through the end of the RSV season.
    • Infants born at 32 to 35 weeks’ gestation who are <3 months of age at the start of the RSV season or who are born during the RSV season if they have one of the following two risk factors:
      • Infant attends child care
      • ≥1 more siblings or other children <5 years of age living permanently in the child’s household
  • Dosage: maximum of 5 monthly doses beginning in November or December at 15 mg/kg per dose IM
  • Current palivizumab guidelines in the Red Book.
COMMONLY ASSOCIATED CONDITIONS
  • Asthma
  • Otitis media
  • Serious bacterial infection (SBI) in infants and children with concurrent RSV infection is rare.
image DIAGNOSIS
PHYSICAL EXAM
  • Vital signs: fever, signs of increased work of breathing (tachypnea, grunting, flaring, retracting), pulse rate; pulse oximetry (“fifth vital sign”) to assess oxygenation
  • Ear, nose, throat: rhinorrhea, dry mucous membranes (dehydration)
  • Serous otitis or acute otitis; pulmonary: wheezing, crackles
  • Skin turgor
  • Serial examinations to assess status
Pediatric Considerations
Young infants with bronchiolitis may develop apnea with increased risk of prolonged hospitalization, ICU admission, and mechanical ventilation.
DIFFERENTIAL DIAGNOSIS
  • Mild illness/URTI
    • Other respiratory viral infections rhinovirus, human metapneumovirus, influenza virus, human bocavirus
    • Allergic rhinitis
    • Sinusitis
  • Severe illness/LRTI
    • Bronchiolitis
    • Asthma
    • Pneumonia
    • Foreign body aspiration
DIAGNOSTIC TESTS & INTERPRETATION
Initial Tests (lab, imaging)
  • Routine laboratory testing is not necessary.
    • If obtained, WBC count may be normal or elevated.
    • Virologic tests for RSV, despite high predictive value, rarely change management decisions or outcomes for patients with clinical bronchiolitis.
  • Given the low risk of SBI, full septic workups are not necessary unless child appears toxic.
  • Chest x-ray (CXR) does not predict disease severity or change patient outcomes but may be helpful if a patient does not improve as expected, if the severity of the disease requires further investigation, or if another diagnosis is suspected.
  • When obtained, typical CXR findings include:
    • Hyperinflation and peribronchiolar thickening
    • Atelectasis
    • Interstitial infiltrates
    • Segmental or lobar consolidation
image TREATMENT
GENERAL MEASURES
  • Assess hydration status and ability to take fluids orally. Treat dehydration adequately with an oral or IV fluid, particularly in infants.
  • Supplemental oxygen is indicated if pulse oximetry falls persistently <90% in previously healthy patients.
MEDICATION
First Line
No first-line medication for RSV infections; treatment is usually supportive; oxygen as needed
P.909

Second Line
  • Bronchodilators show small, short-term improvements in clinical scores, but this small benefit should be weighed against costs and adverse effects.
    • Bronchodilators do not improve oxygen saturation, reduce hospital admission after outpatient treatment, shorten the duration of hospitalization, or reduce the time to resolution of illness at home.
    • Routine use not recommended
  • Nebulized epinephrine is superior to placebo for short-term outcomes for outpatients, particularly in the first 24 hours of care.
    • Epinephrine superior for outpatient clinical outcomes in acute bronchiolitis (4)[A].
  • Glucocorticoids do not alter admissions or length of hospitalization (5)[A].
    • Some data suggest that the combination of dexamethasone and epinephrine may reduce outpatient admissions (5)[A].
  • A recent study found that montelukast (Singulair) has no effect on the clinical course of acute bronchiolitis (6)[C].
  • Ribavirin, a nucleoside analogue and antiviral agent, has not been shown to be efficacious, particularly in immunocompromised patients (7)[A].
  • There is no current evidence that nebulized rhDNase changes clinical outcomes in children <24 months of age hospitalized with acute RSV bronchiolitis (8)[B].
  • Reserve use of antibacterial agents for patients who have specific findings that suggest a coexisting SBI (9)[B].
  • Nebulized 3% saline may reduce the length of stay and improve the clinical severity score in infants hospitalized with acute viral bronchiolitis (10)[A].
ADDITIONAL THERAPIES
  • Bulb suctioning of the nares may provide some comfort to infants and allow for easier feeding.
  • Efforts are underway to develop a RSV vaccine (11)[C].
Pediatric Considerations
Over-the-counter (OTC) cough and cold medications should not be used in children <6 years due to lack of efficacy and the risk of life-threatening side effects.
COMPLEMENTARY & ALTERNATIVE MEDICINE
No complementary, alternative, or integrative therapies are of proven benefit in the prevention or treatment of RSV bronchiolitis.
INPATIENT CONSIDERATIONS
Admission Criteria/Initial Stabilization
  • Clinical judgment of the patient’s degree of respiratory distress is the most important consideration. Ill-appearing infants should be hospitalized.
  • Significant respiratory distress, an oxygen requirement to keep SpO2 >90%, and the inability to hydrate orally are indications for admission.
  • Mechanical ventilation is required in about 5% of infants hospitalized with RSV and 20% of children with underlying congenital heart disease, chronic lung disease, or immunosuppression.
IV Fluids
See “Treatment.”
Discharge Criteria
No set criteria for discharge, patients should be recovering and demonstrate:
  • Stable respiratory status with no oxygen requirement
  • Ability to maintain oral intake and sustain hydration
  • Home resources adequate to support necessary home therapies, including caretaker ability to clear the infant’s airway with bulb suctioning if needed
  • Adequate follow-up and patient education
image ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
Primary care follow-up to ensure resolution
PATIENT EDUCATION
Bronchiolitis and Your Child, available at http://familydoctor.org/familydoctor/en/diseases-conditions/bronchiolitis.html
PROGNOSIS
Most patients with RSV infection recover fully within 7 to 10 days. Reinfection is common.
REFERENCES
1. Byington CL, Wilkes J, Korgenski K, et al. Respiratory syncytial virus-associated mortality in hospitalized infants and young children. Pediatrics. 2015;135(1):e24-e31.
2. American Academy of Pediatrics Subcommittee on Diagnosis and Management of Bronchiolitis. Diagnosis and management of bronchiolitis. Pediatrics. 2006;118(4):1774-1793.
3. DiFranza JR, Masaquel A, Barrett AM, et al. Systematic literature review assessing tobacco smoke exposure as a risk factor for serious respiratory syncytial virus disease among infants and young children. BMC Pediatr. 2012;12:81.
4. Hartling L, Fernandes RM, Bialy L, et al. Steroids and bronchodilators for acute bronchiolitis in the first two years of life: systematic review and meta-analysis. BMJ. 2011;342:d1714.
5. Fernandes RM, Bialy LM, Vandermeer B, et al. Glucocorticoids for acute viral bronchiolitis in infants and young children. Cochrane Database Syst Rev. 2010;(10):CD004878.
6. Amirav I, Luder AS, Kruger N, et al. A doubleblind, placebo-controlled, randomized trial of montelukast for acute bronchiolitis. Pediatrics. 2008;122(6):e1249-e1255.
7. Hynicka LM, Ensor CR. Prophylaxis and treatment of respiratory syncytial virus in adult immunocompromised patients. Ann Pharmacother. 2012;46(4):558-566.
8. Enriquez A, Chu IW, Mellis C, et al. Nebulised deoxyribonuclease for viral bronchiolitis in children younger than 24 months. Cochrane Database Syst Rev. 2012;(11):CD008395.
9. Spurling GK, Fonseka K, Doust J, et al. Antibiotics for bronchiolitis in children. Cochrane Database Syst Rev. 2007;(1):CD005189.
10. Zhang L, Mendoza-Sassi RA, Wainwright C, et al. Nebulized hypertonic saline solution for acute bronchiolitis in infants. Cochrane Database Syst Rev. 2008;(4):CD006458.
11. Poletti P, Merler S, Ajelli M, et al. Evaluating vaccination strategies for reducing infant respiratory syncytial virus infection in low-income settings. BMC Med. 2015;13:49.
Additional Reading
&NA;
  • American Academy of Pediatrics. Section 3: respiratory syncytial virus. In: Pickering LK, Baker CJ, Kimberlin DW, et al, eds. Red Book: 2012 Report of the Committee on Infectious Diseases. 29th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2012.
  • Gadomski AM, Brower M. Bronchodilators for bronchiolitis. Cochrane Database Syst Rev. 2010;(12):CD001266.
Codes
&NA;
ICD10
  • B97.4 Respiratory syncytial virus causing diseases classd elswhr
  • J06.9 Acute upper respiratory infection, unspecified
  • J21.0 Acute bronchiolitis due to respiratory syncytial virus
Clinical Pearls
&NA;
  • RSV causes 50-90% of pediatric bronchiolitis.
  • Hand sanitation is the primary step for preventing RSV in the general population.
  • The diagnosis of RSV is clinical in most cases. Routine lab testing is not necessary.
  • Treatment of RSV is usually supportive.
  • Palivizumab should be used to prevent RSV in high-risk patients.