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Respiratory Syncytial Virus at 50
Table 1: High-risk Groups for Severe Respiratory Syncytial Table 2: Risk Factors for Acquiring Severe Respiratory Syncytial
Virus Infection Virus Infection
Premature infants (≤35 weeks gestational age)
Day-care attendance
Chronic lung disease of infancy (BPD)
School-age siblings
Congenital heart disease
Exposure to environmental pollutants, cigarette smoke
Immunodeficiency disease (e.g. severe combined immunodeficiency disorder)
Neuromuscular disease
Neuromuscular disease
Congenital airway anomalies
Cystic fibrosis
Young chronological age (<10–12 weeks)
Abnormal airway clearance
Low birth weight
BPD = bronchopulmonary dysplasia. Crowded living conditions
Lower socioeconomic status
Increased risk for acquisition of RSV infection at a young age (see Table 2) Maternal education level (≤12th grade)
correlates with increased potential for exposure to the virus from other
Multiple birth sets (≥3)
children or adults, crowding, maternal education level, and factors that
Minimal breast feeding
decrease airway clearance (e.g. environmental pollutants, cigarette smoke).
9,10 Genetic factors
Family history of asthma
The primary clinical manifestation of RSV LRTI in young infants is bronchiolitis
Table 3: American Academy of Pediatrics Guidelines for
characterized by diffuse small-airway disease with tachypnea, retractions,
Consideration of Respiratory Syncytial Virus Prophylaxis
expiratory wheeze, prolonged expiration, rales and rhonci, hypoxemia and
cough, cyanosis, and decreased ability to feed.
11
Small-airway inflammation
I. Premature infants without chronic lung disease or CHD
(pneumonia) is also a frequent part of this illness. RSV infection is usually
1. ≤28 weeks GA and ≤12 months CA at start of RSV season
diagnosed by the typical clinical pattern in conjunction with appropriate 2. 29–32 weeks GA and ≤6 months CA at start of RSV season
seasonality (generally late fall to winter months in temperate climates, or the 3. 32–35 weeks GA,≤6 months CA at start of RSV season, plus ≥2 additional risk
rainy season in tropical regions). Other viral agents (e.g. parainfluenza,
factors (child-care attendance, school-age siblings, exposure to environmental
human metapneumovirus, adenovirus, rhinovirus, influenza, enterovirus)
pollutants, severe neuromuscular disease, congenital airway anomalies)
may also cause clinical bronchiolitis, and the differential diagnosis includes
II. Chronic lung disease of infancy (receiving therapy including supplemental oxygen,
mycoplasma or chlamydia infection, gastroesophageal reflux, inhalation of
diuretics, bronchodilators, or corticosteroids within the past 6 months) and ≤2 years of
age at start of RSV season
toxic substances, reactive airway disease, congestive heart failure, anemia,
III. Hemodynamically significant CHD and ≤2 years of age at start of RSV season
and metabolic acidosis. Specific testing for the presence of RSV in nasal
CHD = congenital heart disease; GA = gestational age; CA = chronological age; RSV = respiratory syncytial virus.
secretions by viral culture and/or antigen detection is readily available in
Source: American Academy of Pediatrics.
22
many clinical laboratories, and a rapid enzyme immunosorbent assay (EIA)
for outpatient testing is available with sensitivities and specificities ranging infections; however, antibiotics are frequently administered to infants
hospitalized with RSV infections.
16,17
The antiviral drug ribavirin was
approved in the US in 1986 for the aerosolized treatment of children with
Prevention of respiratory syncytial virus
severe RSV disease, but, due to the marginal clinical benefit observed, the
infection begins with education
need for prolonged aerosol administration, the high acquisition cost, and
the concern about potential secondary aerosol exposure to the drug in
regarding transmission, decreasing high-
adults of child-bearing age, the drug is used on a very limited basis.
14
Newer,
risk situations for exposure when
more potent antiviral drugs are in development, although the associated
inflammatory responses triggered by RSV infection at the time of clinical
possible, smoking cessation, attention to
presentation may make effective antiviral therapy of established RSV
hand washing, and cleaning of
infection a difficult challenge.
contaminated surfaces.
Prevention of RSV infection begins with education regarding transmission,
decreasing high-risk situations for exposure when possible, smoking
from 69 to 95%.
12
Newer molecular diagnostic tests offer increased cessation, attention to hand washing, and cleaning of contaminated
sensitivity and also can provide information on co-infection with other viruses surfaces. Still, given the ubiquity of the virus and the inability to comply
(e.g. human metapneumovirus).
13
with all of the above control measures, RSV infections continue to occur
at a high rate. For high-risk infants, passive administration of high-titer
Despite the clinical importance of RSV infection, treatment of hospitalized anti-RSV antibodies has been shown to decrease RSV-related
infants remains primarily supportive with attention to airway patency, hospitalizations. RSV-IGIV (RespiGam) was the first product licensed to
oxygenation, and hydration status. Bronchodilators and corticosteroids are decrease RSV hospitalizations in premature infants with or without
frequently administered to babies hospitalized with bronchiolitis, but the chronic lung disease (CLD) of infancy.
18
The requirement for an
clinical trial data do not support their routine use and they are not intravenous line, the large fluid volume per dose, and the nature of the
recommended as part of the standard management of these infants.
14,15
production process limited the use and supply of this product.
Secondary serious bacterial infections occur rarely in the course of RSV Subsequently, a humanized monoclonal antibody, palivizumab (Synagis),
US INFECTIOUS DISEASE 2007 35
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