RSV In-depth for HCW

• RSV, a paramyxovirus, is a large enveloped RNA virus that is highly infectious with two major strains (A and B) circulating concurrently (1,4).
• Although it is the most common cause of lower respiratory tract illness in young children, it may also cause significant morbidity in the older child and adult as well.
• It manifests as tracheobronchitis, bronchiolitis and pneumonia in the very young child, and life threatening infections usually occur during the first two years of life.
• In adults and older children, morbidity from RSV is secondary to acute upper respiratory tract infection, exacerbation of wheezing and bronchitis (4).
• Children with chronic cardiopulmonary disease or immunosuppression are at greater risk of significant morbidity and mortality from RSV.
  

Epidemiology

RSV is the major viral respiratory tract pathogen of early infancy and produces illness with the greatest frequency during the first 2 years of life (2). The spread of RSV in the community can be by the rise in the number of cases of bronchiolitis and pneumonia in the pediatric population as well as a rise in the number of hospital admissions in young children with acute lower respiratory disease. Transmission is by direct or close contact with contaminated secretions which may involve droplets or fomites. RSV can persist on environmental surfaces for many hours and for 30 minutes or more on hands. Health care related spread of RSV to organ transplant recipients or patients with cardiopulmonary abnormalities or immunity compromised condition has been associated with severe and fatal disease in children and adults (1).

Incubation period: ranges from 1 – 10 days (1, 2) 4-6 days is more common (2).

Period of Communicability: shortly prior to and for the duration of active disease (2). Viral shedding is usually 3 – 8 days (1) but may last longer especially in young infants.

Risk of RSV and Associated Clinical Syndromes:

• Bronchiolitis makes up 43-90% of respiratory illnesses caused by RSV in children.
• Pneumonia (5-40%), tracheobronchitis (10-30%) and croup (3-10%) make up the remainder of illnesses caused by RSV (4).

Conditions that increase the risk of severe/fatal RSV infection:

• Cyanotic or complicated congenital heart disease
• Conditions causing pulmonary hypertension
• Underlying pulmonary disease
• Broncho-pulmonary dysplasia
• Prematurity
• Immuno-deficiency disease
• Therapy causing immuno-suppression

Distribution:

• Worldwide, seasonal in temperate zones
• Outbreaks occur reliably every year, most often during late fall, winter and occasionally spring with a predictable and regular pattern.
• RSV activity begins in November, peaks in January and February and continues until April to mid-May for an average of 22 weeks (4). It is also seen in BMT patients throughout the year.
• Boys have a higher incidence of infection than girls (4).
• Of children hospitalized with RSV infection, large proportions of them are from low socioeconomic status (4).
• In general, gender and socioeconomic status influence the severity of infection, not the rate of infection (4).
• Peak incidence of RSV, bronchiolitis and pneumonia is observed at 2 months of age.
• RSV infection rates decrease with increasing age.
  

Clinical Manifestations

RSV in Infants and Young Children

• In young children, RSV infection is manifested primarily as lower respiratory tract disease (i.e. pneumonia, bronchiolitis, tracheobronchiolitis) and upper respiratory tract illness, often with fever and otitis media.
• Pneumonia and bronchiolitis are the most frequent lower respiratory tract illnesses in infants.
• Croup is the least common manifestation of RSV, making up less than 5-10% of cases.
• Pneumonia and bronchiolitis may be difficult to differentiate and both may present with wheezing, rhonchi, rales and infiltrates on chest roentgenograms.
• Bronchiolitis is most commonly associated with wheezing and hyperaeration of the lung.
• Lower respiratory tract disease is usually preceded by upper respiratory tract infection (URI) with nasal congestion and pharyngitis.
• Symptoms of URI include fever (38-40 C) and cough which may be paroxysmal and associated with vomiting.
• After several days of URI symptoms, lower respiratory tract involvement becomes evident.
• Lower respiratory tract illness is characterized by dyspnea, an increase in respiratory rate, retractions of the intercostal muscles, crackles and wheezing on auscultation and multiple areas of interstitial infiltration and hyperinflation of the lung on chest roentgenogram.
• Cyanosis with lower respiratory tract involvement is rare and is usually associated with prolonged hypoxemia.
• The duration of respiratory illness due to RSV infection ranges from 7-21 days.
• Length of hospitalization, if needed, for RSV infection averages 3-7 days.
  Immunity is not complete and reinfection is common (4).
  

RSV in Older Children and Adults

• Secondary infection with RSV, after the first three years of life, is usually manifested as upper respiratory tract illness or tracheobronchitis, however, lower respiratory illness may also occur.
• Common signs and symptoms of URI include nasal congestion and cough.
• Upper respiratory infections with RSV may mimic the common cold but tend to be more severe and prolonged than respiratory illnesses caused by other viral agents such as rhinovirus.
• Symptoms of respiratory illness due to RSV infection in the older child and adult most commonly include fever, runny nose, wheezing and shortness of breath.
• Less commonly, older children and adults may present with sinus pain, ear pain, sore throat and rhonchi and crackles on auscultation.
• Immunity is not complete and reinfection is common (4).
  

Diagnosis

• Diagnosis of RSV in infants with lower respiratory tract illness may be made on the basis of both clinical and epidemiologic findings (4).
• The three most commonly used techniques for viral identification are fluorescent antibody stains of infected nasal epithelium cells, enzyme-linked immunosorbent assay (ELISA) on nasopharyngeal secretions (see NPA directions Link) and viral culture of respiratory secretions (8).
• Viral isolation of nasal wash produces the highest viral recovery and a higher percentage of positive results (4,8).
• All specimens should be inoculated into proper cell lines as soon as possible because the virus is labile when subjected to pH and temperature changes.
• Rapid techniques are also available for diagnosing RSV infection and include immunofluorescent assays, enzyme immunoassay, radioimmunoassays, DNA-RNA hybridization and RNA polymerase chain reaction.
• Ideally cell cultures should be used in addition to a rapid technique in order to confirm diagnosis (4).
  

Complications

Infants

• Young infants and those with underlying diseases are most likely to experience complicated RSV infection.
• 25% - 60% of fatal RSV infections occur in children with cardiopulmonary and congenital disorders.
• Conditions placing young infants at high risk for severe infection with RSV include premature birth, bronchopulmonary dysplasia, cystic fibrosis, congenital heart disease, immunocompromised conditions, neurologic disease, nephrotic syndrome and low birth weight (4).
• Acute complications in infants include apnea and respiratory failure.
• Apnea, as a result of RSV infection, most commonly presents in the first 1-2 months of age, in premature infants and in infants exhibiting moderate to severe hypoxemia.
• There is limited evidence that RSV may contribute to the occurrence of sudden infant death syndrome (SIDS) in infants older than 3 months of age.
• Hypercarbia, respiratory failure and apnea are the major factors leading to assisted ventilation in RSV infected cases (4).
• The role of RSV in the occurrence of wheezing and pulmonary function abnormalities in infants infected and/or hospitalized with RSV at a young age is unknown (4).
  
  

Immunocompromised Patients

• Infants and young children with immunocompromised conditions are at high risk for experiencing complications from RSV infection.
• Suppression of cell mediated immunity is a major factor contributing to the severity of disease in these patients.
• Patients who are severely immunocompromised (i.e. HIV, transplant recipients on immunosuppressive therapy) may exhibit extensive pulmonary infection and prolonged shedding of the virus (4).
  

Treatment

• Primary treatment is supportive and should include hydration, careful assessment of respiratory status, including measurements of O2 saturation, use of supplemental O2, and ventilator support.
• Supplemental oxygen to the hypoxemic patient to maintain oxygen saturation of at least 92%.
• Antibiotic treatment should be reserved for cases where bacterial infection is proven to be complicating infection with RSV.
• Ribavirin:
  • aerosol treatment is generally not recommended (1) and should be only be used on a case-by-case basis a broad spectrum antiviral agent.
  • administered as small particle aerosol in a tent, oxyhood,-mask or ventilator.
  • administered for 8-20 hours per day for 2-5 days. - should be considered for patients with underlying cardiac, pulmonary or immunosuppressive conditions (high-risk cases) (4).
     

Prevention

Infection Control

• Prevention, not treatment, is the goal for the control of RSV infection.
• Prophylactic intervention is problematic due to the very young age at which RSV first attacks.
• Breast-feeding offers some protection to the infant.
• RSV spreads through close contact, direct inoculation of droplets of the secretions from an infected person and indirect transmission from hands that touch infectious secretions that contaminate environmental surfaces.
• Although prevention of infection through interruption of transmission of the virus is difficult in the home and community, preventing transmission in the hospital setting is essential (4).
• The Centers for Diseases Control and Prevention (CDC) recommend the use of droplet precautions for patients with RSV. At JHH, we have used a 2 stage control plan that includes a category of isolation called Pediatric Droplet Precautions. These precautions are similar to the
• CDC's Droplet Precautions. In addition these precautions require that gloves must be worn to enter the room.
• The following link provides a synopsis of the 2 stage control plan used at Johns Hopkins Hospital [RSV 2-Stage Control Plan] (7). Currently, the plan is in effect throughout the Children's Center and a modified version is in place in the oncology center.

RSV Prophylaxis

• RSV-IGIV (RespiGam®) and Palivizumab (Synagis®) are licensed for prophylaxis against RSV and have been approved for use in selected children <24 months with chronic lung disease or history of pre-term birth (gestational age <35 weeks) by the Academy of Pediatrics.
• There is no vaccine available for RSV (4).

 
References

1. American Academy of Pediatrics. (2003). Respiratory syncytial virus. In G. Peter (Ed.), In Red book: Report of the committee on infectious diseases. (23rd ed. , pp. 523-528). Elk Grove Village, IL:Author.
   
   
2. American Public Health Association. (2000). Acute Febrile Respiratory Disease. In J. Chin (Ed.), Control of Communicable Diseases Manual (17th ed., pp. 427-430). Washington, DC.
   
   
3. Glezen, W. P., Taber, L. H., Frank, A. L. & Kasel, J. A. (1986). Risk of primary infection and reinfection with respiratory syncytial virus. American Journal of Diseases of Children, 140, 543-546.
   
   
4. Hall, C. B. & McCathy, C. A. (2000). Respiratory syncytial virus. In G. L. Mandell, J. E. Bennett, & R. Dolin. Principles and Practice of Infectious Diseases. (5th ed., pp. 1782-1801). Philadelphia, PA: Churchill Livingstone.
   
   
5. Hall, C. B., Geiman, J. M., Biggar, R., Kotok, D. I., Hogan, P.M. & Douglas, R. G. (1976). Respiratory syncytial virus infections within families. New England Journal of Medicine, 294, 414-419.
   
   
6. Henderson, F. W., Clyde, W. A., Collier, A.M. & Denny, F. W. (1979). The etiologic and epidemiologic spectrum of bronchiolitis in pediatric practice. Journal of Pediatrics, 95, 183-190.
   
   
7. Karanfil, L. V., Conlon, M., Lykeens, K., Masters, C.F., Forman, M., Griffith, M. E., Townsend, T. R. & Perl, T.M. (1999). Reducing the rate of nosocomially transmitted respiratory syncytial virus. American Journal of Infection Control, 27 (2), 91-96.
   
   
8. Murphy, M. D. (1988). Respiratory syncytial virus. In L. G. Donowitz (Eds.). Hospital Acquired Infection in the Pediatric Patient. Baltimore, MD:Williams and Wilkins.