RESPIRATORY SYNCYTIAL VIRUS (RSV) INFECTION
Elizabeth C. McKeen, MD
BASICS
Respiratory syncytial virus (RSV) is a medium-sized, membrane-bound ribonucleic acid (RNA) virus that causes acute respiratory tract illness in all ages. The most clinically significant disease occurs 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 cytokine- and 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 fusion (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.
DIAGNOSIS
ALERT
In most cases, diagnosis is clinical. Laboratory and radiologic studies are not routinely necessary (2)[B].
HISTORY
• Rhinorrhea and upper respiratory congestion
• Difficulty feeding in infants (due to respiratory effort)
• Increased respiratory rate or signs of increased work of breathing (grunting, flaring, retracting)
• Cough; fever; wheezing
• History of prematurity, secondhand tobacco exposure, daycare, number and age of siblings
• Immunization history
• Family history of respiratory disease
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 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 systemic bacterial infection (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
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.
First Line
No first-line medication for RSV infections; treatment is usually supportive; oxygen as needed
Second Line
• 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 (2)[B]
• Nebulized epinephrine is superior to placebo for short-term outcomes in the outpatient setting, particularly in the first 24 hours (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.
• A recent study found that montelukast (Singulair) has no effect on the clinical course of acute bronchiolitis.
• Ribavirin, a nucleoside analogue and antiviral agent, has not been shown to be efficacious, particularly in immunocompromised patients.
• There is no current evidence that nebulized rhDNase changes clinical outcomes in children <24 months of age hospitalized with acute RSV bronchiolitis.
• Reserve use of antibacterial agents for patients who have specific findings that suggest a coexisting SBI.
• Nebulized 3% saline may reduce the length of stay and improve the clinical severity score in infants hospitalized with acute viral bronchiolitis.
• Heliox therapy may significantly reduce a clinical score evaluating respiratory distress in the first hour after starting treatment for infants with acute bronchiolitis, but there does not seem to be a reduction in the rate of intubation, in the rate of emergency department discharge, or in the length of treatment for respiratory distress (5)[A].
ADDITIONAL THERAPIES
• Bulb suctioning of the nares may provide some comfort to infants and allow for easier feeding.
• Efforts are underway to develop an RSV vaccine (6)[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.
ADMISSION, INPATIENT, AND NURSING CONSIDERATIONS
• 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.”
• 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
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.
COMPLICATIONS
• Infants hospitalized for RSV may be at increased risk for recurrent wheezing and reduced pulmonary function, particularly during the 1st decade of life.
• Overall mortality for infants and children <24 months of age is <1%.
• Although the relationship between RSV and asthma is unclear, RSV bronchiolitis in infancy has been linked to subsequent asthma.
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. Ralston SL, Lieberthal AS, Meissner HC, et al. Clinical practice guideline: the diagnosis, management, and prevention of bronchiolitis. Pediatrics. 2014;134(5):e1474–e1502.
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. Liet JM, Ducruet T, Gupta V, et al. Heliox inhalation therapy for bronchiolitis in infants. Cochrane Database Syst Rev. 2015;(9):CD006915.
6. 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
• American Academy of Pediatrics. 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.
• Haynes AK, Prill MM, Iwane MK, et al. Respiratory syncytial virus circulation in the United States, July 2012–June 2014. MMWR. 2014;63(48):1133–1136.
• Gadomski AM, Brower M. Bronchodilators for bronchiolitis. Cochrane Database Syst Rev. 2010;(12):CD001266.
CODES
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
• 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 or radiology studies are not necessary.
• Treatment of RSV is usually supportive.
• Palivizumab should be used to prevent RSV in high-risk patients.