Biology Reference
In-Depth Information
15.1
Introduction
15.1.1
RSV Epidemiology and Diagnosis
RSV is the most commonly identified viral cause of moderate-to-severe acute upper
and lower respiratory tract infection (LRTI) in infancy. The global burden of RSV
infection is high, with an estimated 34 million episodes of LRTI occurring in children
under 5 years old, resulting in an estimated death rate from 66,000 to 200,000 per year
[ 1 ]. Healthy adults also are infected with RSV repetitively over their lifetime, but
typically have a milder course that is confined to the upper respiratory tract. However,
in both elderly and immunocompromised adults, RSV can cause severe and life-
threatening pneumonitis as well as lead to a deterioration in underlying cardiac or
pulmonary disease [ 2- 4 ]. Importantly, elderly patients requiring hospitalization for
RSV infection have similar lengths of stay, rates of intensive care use, and mortality
(~11,000 deaths per year) as elderly patients with influenza A infection [ 2 ] .
RSV is a single-stranded RNA virus that is a member of the Paramyxoviridae
family. Two major human RSV subtypes, A and B, have pathogenic roles in lower
respiratory tract infections, with the A subtype reported to cause a more severe
disease [ 5 ]. Surveillance data from the Centers for Disease Control indicate that
the most widespread RSV activity occurs between November and May in the
Northern Hemisphere ( http://www.cdc.gov/surveillance/nrevss/rsv/natl-trend.
html ). Transmission of RSV occurs by inoculation of the nasopharyngeal or ocular
mucosa after contact with virus-containing secretions. While the mechanism by
which RSV infects a cell has not been fully elucidated, RSV attaches to the host cell
via its surface glycoprotein (G) and enters the cell via binding of its fusion protein
(F) to the host epithelial cell membrane [ 6 ]. Once inside the cell, RSV replication is
facilitated by the nucleocapsid (N) protein. After replicating in the epithelial cells of
nasopharynx, RSV can spread to the bronchiolar epithelium of the lower respiratory
tract via cell-to-cell spread or aspiration of secretions. A monoclonal antibody
(Palivizumab, Synagis ® ) that targets the fusion protein of RSV and prevents
F-protein-mediated cell entry has been approved in 45 countries worldwide for the
prevention of RSV in high-risk pediatric patients [ 5, 6 ]. Drugs that block RSV
attachment, fusion, or replication have been developed, but to date, only two are in
Phase II clinical trials, and both of these drugs target the N protein [ 7 ] . The diagno-
sis of RSV in respiratory secretions (nasal swab/wash, oropharyngeal wash, bron-
choalveolar lavage) can be made by various different assays including viral culture,
detection of viral antigens, and detection of viral RNA (PCR-based assays).
15.1.2
Current RSV Treatment Strategy
The treatment of a LRTI secondary to RSV in children is mainly supportive, with
oxygen typically given to those patients requiring hospitalization. The need for
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