A. Properties of RSV

1. Two major serotypes, RSV A (~60% of cases) and RSV B
2. Negative stranded RNA virus
   1. 15,222 nucleotides in length
   2. Codes for 10 major proteins
   3. F (fusion) and G (attachment) proteins are major surface antigenic determinants
   4. Matrix (M) and small envelope (M2) proteins
   5. Nucleocapsid associated (N, NP, P, and polymerase complex) proteins
   6. Small hydrophobic structural protein of unknown function
   7. Two nonstructural proteins with unknown function
3. Common cause of acute upper (and some lower) respiratory infections [3]
   1. About 4 million cases per year, mainly in children under 4 years old
   2. Nearly all children have been infected by the age of two [4]
   3. Risk of RSV increased with 3 or more siblings and in daycare settings
   4. >100,000 hospitalizations per year
   5. Increasing deaths associated with RSV: ~17,000 per year in USA [3]
   6. ~80% of deaths associated with RSV in patients >64 years
4. Season is December through April, peak in January and February
   1. Both influenza and RSV are common in children [3,5]
   2. Influenza most common November through February
   3. RSV most common January through March
   4. RSV infection often incorrectly diagnosed as influenza [6]
   5. Very common cause of "common cold" and influenza-like illness in all ages [6]
   6. Severe disease progresses to bronchiolitis which can be fatal
5. Major problem in developing countries

B. RSV Disease

1. Acute respiratory disease in both children and adults
   1. Causes ~20% of cases of croup
   2. Usually causes bronchiolitis in children
2. Bronchiolitis
   1. Infection of lower respiratory tract which occurs in persons <1 year old
   2. Most commonly associated with RSV
   3. Exposure to tobacco smoke may increase risk
   4. Wheezing is a common component (along with shortness of breath)
   5. Dexamethasone (1mg/kg) had no benefit over placebo in 120 infant trial [7]
   6. Large amounts of interleukin 9 from neutrophils found in severe bronchiolitis [8]
3. Severe Complications - pneumonia and bronchiolitis
   1. Premature infants
   2. Infants with bronchopulmonary dysplasia (BPD) or cardiac disease
   3. Infants 2-6 months of age
   4. Children with underlying cardiac or pulmonary disease or immunodeficiency
   5. Adults with immuoncompromise
   6. May be nosocomial infection
4. RSV in Adults [9]
   1. Upper respiratory tract infection (URI) usually in adults ("influenza-like illness)
   2. RSV infection develops in ~5% of healthy elderly patients annually
   3. RSV infection develops in ~7% of high-risk adults annually
   4. RSV and influenza A appear to cause about the same prevalence of disease in adults
   5. RSV involved in ~11% of hospitalizations for pneumonia and COPD
5. Cellular immunity plays key role in recovery from RSV infection

C. Diagnosis

1. High suspicion
2. Nasopharyngeal aspirates or washes
   1. Immunofluorescence - more sensitive
   2. ELISA - more easily performed
3. Routine culture or shell viral system for isolating virus - no longer preferred

D. Criteria for Hospital Admission [2]

1. Severe Disease
   1. Poor or non-responsiveness
   2. Inability to feed
   3. Hypoxea unresponsive to low flow (<1L/min) oxygen
   4. Apnea
2. Moderate Disease
   1. Consider admission after observation
   2. Poor feeding
   3. Signs of dehydration
   4. Oxygen requirement that cannot be administered at home
3. Underlying Disease
   1. Consider admission (low threshold)
   2. Bronchopulmonary dysplasia
   3. Prematurity
   4. Congenital heart disease
   5. Congenital pulmonary malformations
   6. Immune compromise
4. Complicated Disease
   1. Suspected Sepsis
   2. Malnutrition
   3. Age <6 weeks
5. Uncertain home care may also be criteria for admission

E. Treatment

1. Ribavirin
   1. Antiviral agent with some activity against RSV
   2. Some efficacy in children used in aerosolized form
   3. Efficacy has not been definitively demonstrated
   4. Combination with RSV immune globulin may be more effective
   5. This combination may be reserved for life-threatening situations
   6. Aerosolized ribavirin is difficult to give as it causes marked wheezing
2. Supportive Care
   1. Mechanical ventilation
   2. Antibiotics are not indicated
3. Bronchodilator Therapy (? efficacy)
4. Hospital Discharge Criteria [2]
   1. Adequate oral intake
   2. Improved work of breathing
   3. Oxygen saturation >90% on room air or low flow nasal oxygen (maintained)
   4. Avoid ALL smoke exposure

F. Prophylaxis

1. Intravenous RSV immune globulin (RespiGam®)
   1. FDA approved for high risk persons
   2. Used as prophylaxis in high risk patients (as above) and all premature infants
2. Pavlivizumab (Synagis®) [10,11]
   1. Palivizumab is humanized Mc Ab against the F glycoprotein of RSV
   2. Palivizumab is given once monthly from November to April to premature infants
   3. Also recommended to other high risk populations
   4. May be better tolerated than RSV immune globulin
   5. Given via Intramuscular (IM) injection
3. Indications for Pavlivizumab [11]
   1. American Academy of Pediatrics recommendations for prophylaxis
   2. Children <2 years old with chronic lung disease who have required therapy within 6 months
   3. Infants <1 year old born at <29 weeks' gestation
   4. Infants <6 months old born 29-32 weeks
   5. Infants <6 months old born 32-35 weeks who have additional risk factors for RSV infection
4. Vaccines are being developed
   1. T cell immunity is likely required
   2. However, infection once is not necessarily protective for next infection

References

1. Hall CB. 2001. NEJM. 344(25):1917
2. Simoes EAF. 1999. Lancet. 354(9181):847
3. Thompson WW, Shah DK, Weintraub E, et al. 2003. JAMA. 289(2):179
4. Respiratory Syncytial Virus. 2000. MMWR. 49:1091
5. Izurieta HS, Thompson WW, Kramarz P, et al. 2000. NEJM. 342(4):232
6. Zambon MC, Stockton JD, Clewley JP, Fleming DM. 2001. Lancet. 358(9291):1410
7. Roosevelt G, Sheehan K, Grupp-Phelan J, et al. 1996. Lancet. 348:292
8. McNamara PS, Flanagan BF, Baldwin LM, et al. 2004. Lancet. 363(9414):1031
9. Falsey AR, Hennessey PA, Formica MA, et al. 2005. NEJM. 352(17):1749
10. Palivizumab. 1999. Med Let. 41(1043):3
11. Palivizumab. 2001. Med Let. 43(1098):13