Respiratory Syncytial Virus

Aka: Respiratory Syncytial Virus, Bronchiolitis, RSV, Metapneumovirus

1. Epidemiology: RSV
   1. Incidence: 2.1 Million children under age 5 years seek medical attention for RSV annually in the U.S.
   2. Annual epidemics occur winter to early spring
      1. Range: November to April
      2. Peak: January to February
   3. Overall hospitalization rate: 1-2% (90,000 per year in United States)
   4. Attack rates
      1. Daycare exposure: 100% infection rate
      2. Sibling exposure: 40% infection rate
   5. Cohorts Affected
      1. Children under age 2 years (usually 1-6 months old)
      2. Of infants at risk, 50% will be infected
         1. By age 2 years, nearly all children will have had one RSV infection (at least 90%)
            1. Prior infection is no protection against future infection
         2. RSV associated hospitalizations
            1. RSV hospitalizations due to Pneumonia: 20-25%
            2. RSV hospitalizations due to Bronchiolitis: 75%
      3. Older children and adults
         1. Common Cold-like Syndrome
         2. Rhinorrhea, Sore Throat, and cough
      4. Elderly and Immunocompromised patients
         1. Severe Pneumonia may result
2. Risk Factors
   1. Prematurity
   2. Complex Congenital Heart Disease
   3. Chronic lung disease
   4. Immunosuppression
   5. Neuromuscular disease
   6. Metabolic disorder
   7. Staat (2002) Semin Respir Infect 17:15-20
3. Pathophysiology: RSV
   1. Enveloped, nonsegmented, negative-strand RNA virus (Paramyxoviridae Family)
      1. Subtypes A (causes more severe disease)
      2. Subtypes B
   2. Transmission
      1. Close contact
      2. Fingers or fomites
      3. Self inoculation of Conjunctiva or anterior nares
      4. Coarse aerosols from coughing or sneezing
   3. Viral load peaks at 4 to 5 days
      1. Corresponds to peak illness severity at 3-5 days
   4. Incubation: 2 to 8 days
   5. Virus shedding: 3-8 days (up to 4 weeks in infants)
   6. Duration of illness (under age 2 years)
      1. Median: 12 days
      2. Prolonged in 10% of cases as long as 4 weeks
   7. Re-infection with different RSV forms is common
      1. Prior RSV infection confers no immunity against new infection
   8. Infectious course
      1. Viral replication starts in the nasopharynx
      2. Spreads to the small Bronchiole epithelial lining
      3. Lower respiratory tract infection onset within 3 days with increased airway edema and mucous production, and ultimately tissue necrosis
      4. Results in small airway obstruction, air trapping and increased airway resistance
4. Causes: Bronchiolitis
   1. Respiratory Syncytial Virus (RSV)
   2. Parainfluenza
   3. Influenza
   4. Adenovirus
   5. Metapneumovirus (MPV)
      1. Emerging paramyxovirus
      2. Similar presentation as RSV
      3. Hamelin (2004) Clin Infect Dis 38:983-90
5. Symptoms
   1. Typical symptoms in infants and young children
      1. Cough (98%)
      2. Low grade fever (75%)
      3. Labored breathing (73%)
      4. Wheezing (65%)
      5. Rhinorrhea
      6. Mild systemic symptoms
   2. Typical symptoms in older children
      1. Cough
      2. Coryza
      3. Rhinorrhea
      4. Conjunctivitis
   3. Severe illness
      1. Grunting
      2. Nasal flaring
      3. Intercostal retractions
      4. Tachypnea or Dyspnea
      5. Hypoxia and cyanosis
      6. Apparent Life Threatening Event or Apnea
         1. Premature infants or very young infants are at increased risk
         2. May occur without other signs of respiratory distress
6. Signs
   1. Diffuse Wheezing
   2. Rhonchi
   3. Rales
7. Differential Diagnosis
   1. See Wheezing
   2. Reactive airway disease
8. Evaluation: Non-toxic infants ages 60-90 days of age
   1. Non-toxic febrile infants at 60-90 days with Bronchiolitis do not need a bacteremia work-up
   2. Blood Cultures and Lumbar Puncture are not needed
   3. Urinalysis and Urine Culture should still be performed
   4. Ralston (2011) Arch Pediatr Adolesc Med 165(10):951-6
9. Labs
   1. Blood Cultures not needed in routine cases
   2. RSV swabs or washings of nasopharynx, throat, or Sputum
      1. RSV is a clinical diagnosis and testing is optional
      2. Efficacy
         1. Test Sensitivity: 80-90%
         2. Test Specificity: 90-99%
      3. Indications
         1. Other diagnosis considered (Sepsis)
         2. Inpatient room placement (shared inpatient rooms)
         3. Epidemiologic data to define start of outbreak
   3. Urinalysis and Urine Culture
      1. Consider in patients with RSV severe enough to consider admission
      2. Urinary Tract Infections are present in 12% of RSV cases
   4. RSV is associated with a decreased risk of other conditions
      1. Decreased risk of Meningitis
      2. Decreased risk of bacteremia
10. Imaging: Chest XRay
    1. Hyperexpansion
    2. Peribronchial thickening
    3. Variable infiltrates or Viral Pneumonia
11. Management
    1. Hospitalization Indications
       1. Apnea risk
          1. RSV in infant under 2 months of age
          2. Gestational age at birth <35 weeks
       2. Comorbidity
          1. Comorbid cardiopulmonary disease
          2. Comorbid Immunodeficiency
       3. Respiratory distress
          1. See Respiratory Distress in Children with Pneumonia
          2. See Pediatric Early Warning Score (PEWS Score)
          3. Respiratory Rate >60 breaths per minute
             1. See Tachypnea for criteria based on age
          4. Wheezing
          5. Oxygen Saturation <90%
          6. Lethargy
          7. Hypercarbia
          8. Chest XRay changes (e.g. Atelectasis)
    2. General Measures
       1. Constantly reassess for signs of impending respiratory failure
          1. May be signaled by a 'normalization' of the Respiratory Rate (due to respiratory muscle Fatigue)
       2. Humidified Oxygen to keep Oxygen Saturation at 90% or better
       3. Hydration
       4. Suctioning of secretions
          1. Includes gentle Nasal Saline with suctioning (avoid trauma and secondary edema)
    3. Nebulizer
       1. Nebulized Albuterol
          1. May be effective in up to 50% of RSV patients (especially for children with history of Asthma or atopy)
          2. If improvement with trial then continue every 6 hours (if not, then supportive care only)
          3. Background
             1. Albuterol does not improve oxygenation in RSV
             2. Albuterol does not shorten hospital stay in RSV
             3. Albuterol may offer minor symptomatic relief in RSV
          4. References
             1. Turner (2003) Ann Emerg Med 42:709-11
       2. Nebulized Atrovent
          1. See Reactive Airway Disease
          2. Some evidence as of 2011 suggesting Atrovent is effective
       3. Nebulized racemic epinephrine
          1. Variable efficacy
          2. Use has declined since 2007
          3. Requires 2-4 hours of observation after administration due to transient effect with risk of rebound
          4. Wainright (2003) N Engl J Med 349:27-35
       4. Hypertonic Saline Nebulization
          1. Nebulizer dose: 4 ml of 3% hypertonic saline
          2. May shorten hospital stay
          3. Not effective in preventing hospitalization (may not be as useful for emergency care)
          4. Zhang (2008) Cochrane Database Syst Rev :CD006458
    4. Systemic Corticosteroids
       1. Do not decrease severity of illness or shorten the disease course
       2. Not recommended by American Academy of Pediatrics
       3. Atopic Patients and older patient's with Asthma may benefit
       4. Data is mixed and some studies have shown benefit (e.g. Systemic Dexamethasone with Nebulized Epinephrine)
          1. Csonka (2003) J Pediatr 143:725-30
          2. Plint (2009) N Engl J Med 360(20): 2079-89
    5. Montelukast
       1. Improved post-RSV clinical symptoms (age 3-36 months)
       2. Bisgaard (2003) Am J Respir Crit Care Med 167:379-83
    6. Severe cases
       1. Severe Hypoxia may require intubation
       2. Helium-Oxygen therapy
          1. Martinon-Torres (2002) Pediatrics 109:68-73
       3. Surfactant
          1. Tibby (2000) Am J Respir Crit Care 162:1251-6
       4. Aerosolized Ribavirin (Virazole)
          1. Use limited to immunosuppressed children with severe disease
          2. May be useful early at maximal viral load
          3. Variable efficacy
          4. Cost exceeds $1000 per day
          5. Randolph (1996) Arch Pediatr Adolesc Med 150:942-7
12. Management: Therapies not found to be useful
    1. Theophylline does not change the clinical course
    2. Antibiotics without bacterial infection identified
    3. Inhaled Interferon alfa-2a
    4. RSV Immune globulin for acute treatment
       1. Indicated for prophylaxis in high risk infants
       2. No evidence for benefit in acute disease
    5. Palivizumab for acute treatment
       1. Indicated for prophylaxis in high risk infants
       2. No evidence for benefit in acute disease
13. Prevention
    1. General measures
       1. Avoid contagious exposures
       2. Avoid Passive Smoke Exposure
       3. Hand washing
    2. Medications
       1. RSV Immune Globulin (RSV-IG, Respigam)
       2. Palivizumab (Synagis)
          1. Given monthly for up to 5 months of RSV season (November 1 to March 1)
          2. See Palivizumab for indications
             1. Premature infants born before 35 weeks gestation
             2. Cyanotic Congenital Heart Disease
             3. Chronic lung disease (Bronchopulmonary Dysplasia)
             4. Neuromuscular disorders
14. Prognosis
    1. Overall RSV case fatality rate: 1%
       1. Deaths: 372 per year in United States (90% are under age 1 year)
    2. More severe illness if comorbid underlying disease
       1. Congenital Heart Disease (RSV Mortality 37%)
       2. Bronchopulmonary Dysplasia
       3. Immunosuppression
       4. Age <3 months
       5. Weight <11 pounds (5 kg)
       6. Premature birth (<35 weeks gestation)
    3. Persistent reactive airway disease
       1. Wheezing episodes persist up to 5 years in 40% of children with RSV infection
       2. Wheezing episodes persist beyond 5 years in 10% of children with RSV infection
15. References
    1. Dawson-Caswell (2011) Am Fam Physician 83(2): 141-6
    2. Panitch (2003) Pediatr Infect Dis J 22:S83-8
    3. Jafri (2003) Pediatr Infect Dis J 22:S89-93
    4. Steiner (2004) Am Fam Physician 69:325-30