Current Diagnosis & Treatment in Infectious Diseases

Section IV - Viral Infections

31. Respiratory Syncytial Virus

Gregory Sonnen MD

Nancy Henry MD, PhD

Essentials of Diagnosis

  • Most important respiratory pathogen of infancy.
  • Passively acquired maternal antibodies provide no protection.
  • Can infect upper and lower respiratory tract.
  • Symptomatic reinfection occurs throughout life.
  • Children with pulmonary or cardiac disease can have serious morbidity from infection.
  • Yearly reinfection is common throughout life.

General Considerations

  1. Epidemiology.Respiratory syncytial virus (RSV) produces a yearly epidemic in temperate climates. Most commonly, it causes bronchiolitis but can also cause upper respiratory infections, tracheobronchitis, and pneumonia (Table 31-1). In the United States, RSV activity is greatest from December through April. Some variation occurs year to year. The epidemic lasts from 2 to 5 months. Essentially all children are infected during the first 3 years of life. Yearly reinfection is common throughout life. The virus is responsible for ~90,000 hospital admissions and 4,500 deaths/year in the United States.
  2. Microbiology.RSV is a 120- to 300-nm enveloped RNA virus of the Paramyxoviridaefamily. It is in the genus Pneumovirus. The viral RNA encodes 10 proteins, 7 of which are structural (F, G, L, M, N, P, and SH). Two antigenic strains have been identified and are differentiated based on the G surface glycoprotein. The epidemiologic and clinical significance of the antigenic variation is unknown. The virus is very labile regarding temperature variation; however, the lability of this virus does not reflect on its high degree of communicability.
  3. Pathogenesis.The virus is transferred via droplet nuclei, direct contact, and fomites. The virus has been shown to remain viable on fomites for hours and on the human hand for ≥ 30 min. Nosocomial infections are very frequent and warrant strict adherence to hospital isolation procedures.

RSV adheres to and invades the respiratory epithelium. It has an incubation period of 2–8 days. The virus spreads cell to cell via intracytoplasmic bridges. It has potential to cause pathologic changes along the entire respiratory tract. Pulmonary pathology commonly noted during autopsy of infants with RSV bronchiolitis includes peribronchiolar mononuclear infiltration, epithelial necrosis of bronchioles, luminal plugging, airway hyperinflation, and atelectasis. Patients with RSV pneumonia also show evidence of mononuclear interstitial infiltration.

CLINICAL SYNDROMES

BROANCHIOLITIS

Clinical Findings

  1. Signs and Symptoms.Bronchiolitis is an acute respiratory illness affecting primarily infants (Box 31-1). RSV is the most common etiology. Patient ages range from 6 weeks to 2 years, with a peak incidence from 2 to 6 months of age. Presenting symptoms commonly include low-grade fever, clear rhinorrhea, tachypnea, cough, and expiratory wheezing. Hypoxemia and respiratory failure may occur in advanced or complicated cases. Dehydration may be present owing to increased insensible fluid losses and poor intake of fluids.
  2. Laboratory Findings.Viral isolation and antigen testing are performed from nasopharyngeal washings. Instillation of 1–2 cc of sterile saline in a nasal passage followed by prompt suction with an in-line suction trap will obtain a good specimen. Culturing requires 3–5 days and is optimal on human heteroploid, monkey kidney, human kidney, and fibroblast cells. Viral antigen can be detected with an immunofluorescence assay or enzyme immunoassay.
  3. Imaging.Chest radiographs commonly display hyperinflation. Occasionally atelectasis or diffuse infiltrates are seen.
  4. Differential Diagnosis.The differential diagnosis of bronchiolitis includes pneumonia, asthma exacerbation, foreign-body aspiration, and noxious-chemical inhalation.
  5. Complications.In healthy infants, the disease lasts 3–7 days. Children with an underlying pulmonary or cardiac disease can have prolonged courses lasting weeks. Recurrent episodes of wheezing may occur in ≤ 50% of infants infected by RSV. The wheezing may last until 3 years of age.

Table 31-1. RSV clinical findings.

Syndrome

Age Group

Clinical Findings

Upper respiratory tract illness

o   More common in older children and adults

o   Cough

o   Profuse rhinorrhea

o   Serous otitis media

o   Pharyngitis

Tracheobronchitis

o   All ages

o   Hoarseness

o   Cough

Bronchiolitis

o   Range of 6 weeks to 2 years

o   Peak of 2–6 months

o   Tachypnea

o   Cough

o   Expiratory wheezing

o   Clear rhinorrhea

o   Radiographic evidence of pulmonary hyperinflation

o   Low-grade fever

Pneumonia

o   Infants, toddlers, & the elderly

o   Respiratory distress

o   Diffuse, fine rales

o   Radiographic evidence of diffuse interstitial infiltrates

o   Fever

PNEUMONIA

  1. Signs and Symptoms.Pneumonia from RSV typically occurs in infants and the elderly. Typical presenting symptoms may include fever, dyspnea, tachypnea, and hypoxemia. Diffuse, fine rales may be auscultated.
  2. Laboratory Findings.Same as laboratory findings for bronchiolitis (above).
  3. Imaging.Chest radiography demonstrates diffuse interstitial infiltrates.
  4. Differential Diagnosis.Exclusion of a bacterial etiology may be difficult.
  5. Complications.Patients with underlying pulmonary, immunologic, and cardiac disease are at risk for serious morbidity.

BOX 31-1 RSV Syndromes

More Common

· Bronchiolitis (primarily infants)

· Pneumonia

· Tracheobronchitis

· Upper respiratory tract ilness

· Asthma exacerbation

· Upper respiratory tract illness

· Asthma exacerbation

Less Common

· Otitis media

· Tracheobronchitis

· Pneumonia (primarily the elderly)

Diagnosis

Diagnosis of most RSV infections is based on physical and radiographic findings (see Table 31-1). Rapid antigen detection is often helpful, especially in compromised infants. Evidence of hypoxemia at presentation warrants aggressive therapy.

Treatment

Therapy is aimed at maintaining oxygenation and adequate air exchange. Supportive care is effective in the vast majority of cases. Tachypneic infants will have increased insensible fluid losses. Intravenous fluids may be needed if dehydration is present. Nasal suctioning to maintain clear nasal passages is warranted in all infants. Oxygen should be provided immediately if hypoxia is present. Bronchodilators may provide some benefit in bronchiolitis. Mechanical ventilation is indicated if signs of respiratory failure are present. Corticosteroids will benefit if the patient has asthma.

BOX 31-2 Treatment of RSV

Condition

Indications

Dosage

Supportive Care

· All uncomplicated cases of bronchiolitis and pneumonia

· Humidified oxygen

· Antipyretics

· Parenteral hydration, if needed

Mechanical Ventilation

· Respiratory failure

· Titrate to maintain oxygenation and adequate air exchange

Immunoprophylaxis with Palivizumab Intramuscular Monoclonal Antibody Injection

· Infants < 2 years old with bronchopulmonary dysplasia who require oxygen or have needed oxygen in the 6 months before RSV season

· Infant < 1 year old with bronchopulmonary dysplasia who are on any chronic respiratory treatment

· Infants < 1 year old with a gestational age of ≤28 weeks at birth

· Infants < 6 months old with a gestational age of 29-32 weeks at birth

· Infants < 6 months old with a gestational age of 32-35 weeks who have passive exposure to smoke, attend day care, or experience other pulmonary risk factors

· Not FDA approved alone for congenital heart disease

· Contraindicated in cyanotic congenital heart disease

· 15 mg/kg intramuscularly in the anterolateral thigh

· Dose is given montly from November through April in most temperate climates. Consult local health officials for RSV epidemiology in specific regions

I-β-D-Ribofuranosyl-1,2,4-triazole-3-carboxamide (Ribavirin)

· Complex congenital heart disease

· Pulmonary hypertension

· Bronchopulmonary dysplasia

· Chronic lung disease, including cystic fibrosis

· Immunosuppressed state

· Premature birth (less than 37 weeks gestation)

· Healthy infants less than 6 weeks of age

· Severely ill and recalcitrant to supportive measures

· Administer 6 g, diluted to 20 mg/ml, aerosolized over 12 to 18 hours for 3 to 7 days. Administered via Viratek Small Particle Aerosol Generator (SPAG 2)

· For maximum efficacy, ribavirin should be administered as early as possible after onset of symptoms

· Avoid use in pregnant women

· Ribavirin may interfere with some mechanical ventilators

Corticosteroids

· Virus-induced asthma

· No proven benefit in healthy infants with uncomplicated bronchiolitis

· Prednisone (or equivalent) 1 mg/kg divided twice a day for 5 d (max dose = 60 mg/d)

· Higher doses are indicated in some cases and should be used with caution

Bronchodilators

· Asthma or clinical evidence of bronchospasm

· Benefit is controversial in healthy infants with uncomplicated bronchiolitis

· Albuterol 0.5%, 0.05 to 0.15 mg/kg dose nebulized every 4 h (max dose = 2.5 mg/dose)

· Higher doses are indicated in some cases and should be used with caution

Immunoprophylaxis is highly effective if used appropriately (Box 31-2). Administration of ribavirin should be reserved for severe, refractory cases and infants compromised by cardiac, pulmonary, or immunologic disease. A history of prematurity also warrants consideration of ribavirin use. Ribavirin does interfere with some mechanical ventilators and small endotracheal tubes. Extreme caution should be observed with its use.

Prevention & Control

Thorough hand washing will limit the spread of RSV (Box 31-3). No vaccine is currently available. Immunoprophylaxis is effective in high-risk infants. Droplet isolation of the hospitalized patient is indicated. Strict isolation may be indicated in some hospital environments. Hospital isolation procedures should be strictly enforced. RSV is a common source of nosocomial infection. Symptomatic children should be excluded from school or daycare. Viral shedding usually lasts from 3 to 8 days after the onset of symptoms. Rare cases may shed virus for as long as 4 weeks.

BOX 31-3 Prevention & Control of RSV

Prophylactic Measures

· Hand washing, disinfection of fomites

· RSV vaccine is in clinical trials

· Immunoprophylaxis for high-risk infants (see Box 31-2)

Isolation Precautions

· Droplet isolation for hospitalized patients; strict isolation may be indicated in certain environments

· Children should be excluded from school and daycare until symptoms resolve

· Viral shedding can last as long as 4 weeks; usually 3 to 8 d

REFERENCES

American Academy of Pediatrics, Committee on Infectious Diseases: Prevention of RSV: Indications for the use of Palivizumab and update on the use of RSV-IGIV. Pediatrics 1998;102:1211.

American Academy of Pediatrics, Committee on Infectious Diseases: Reassessment of indications for ribavirin therapy. Pediatrics 1996;97:137.

American Academy of Pediatrics, Committee on Infectious Diseases: Respiratory syncytial virus. In Peter G, (editor): 1997 Red Book: Report of the Committee on Infectious Diseases, 24th ed. American Academy of Pediatrics, 1997.

American Academy of Pediatrics, Committee on Infectious Diseases, Committee on Fetus and Newborn: Respiratory syncytial virus immune globulin intravenous: Indications for use. Pediatrics 1997;99:645.

Groothuis JR et al: Prophylactic administration of respiratory syncytial virus immune globulin to high-risk infants and young children. N Engl J Med 1993;329:1524.

Hall CB: Respiratory syncytial virus. In Feigin RD, Cherry JD (editors): Textbook of Pediatric Infectious Diseases, 3rd ed. Saunders, 1992.