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Respiratory viral infections are a major cause of morbidity in children around the world. Healthy infants and preschool children experience between 6 and 10 respiratory illnesses per year, and school-age children and adolescents experience 3 to 5 illnesses annually. Respiratory viral infections are classified into (1) upper respiratory tract infections (URIs), also known as the common cold, rhinitis, pharyngitis, otitis media, and conjunctivitis; and (2) lower respiratory tract infections (LRTIs), namely croup, laryngitis, tracheobronchitis, bronchiolitis, and pneumonia. With molecular techniques becoming the new gold standard for the detection of respiratory viruses, important changes have occurred in our understanding of the role of these viruses in respiratory illnesses in children, particularly in LRTIs. Newly discovered viruses have been identified in the last decade (eg, human bocaviruses, human coronaviruses) that have been associated with respiratory illnesses. In addition, areas that require further research have been uncovered such as the causality between newly discovered viruses and clinical disease, the significance of viral co-detections, and the role of viral quantitation and its correlation with disease severity. Despite these changes, epidemiologic studies have demonstrated that the major associations established by traditional techniques (eg, viral culture, antigen detection, and serology) remain valid. Despite the major advances observed with the development of diagnostic tools, there has been a paucity of major changes in the availability of specific antivirals and vaccines, although many are currently under investigation with the potential to become available in the next few years.
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RESPIRATORY SYNCYTIAL VIRUS
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Respiratory syncytial virus (RSV) is the leading cause of viral lower respiratory tract disease in infants and toddlers. It accounts for approximately 60% of all LRTIs in preschool-aged children worldwide. In the developing world, RSV is second only to malaria as a cause of death during the first year of life. Severe disease is generally associated with primary infection, although LRTI can also occur upon reinfection. Bronchiolitis, which refers to inflammation of smaller intrapulmonary airways, is the single most distinctive clinical syndrome of RSV infection.
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PATHOGENESIS AND EPIDEMIOLOGY
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RSV belongs to the genus Pneumovirus within the Paramyxoviridae family. It is an enveloped, single-stranded, negative-sense RNA virus with a diameter spanning 100 to 350 nm. The viral envelope is studded with spike-like projections that include the fusion (F) and attachment (G) surface glycoproteins, but unlike most paramyxoviruses, RSV surface proteins lack both hemagglutinin (HA) and neuraminidase (NA) activity. The G protein initiates the infection, while the F glycoprotein mediates viral penetration by fusing viral and cellular membranes, contributing to syncytia formation. These 2 proteins carry the antigenic determinants that elicit the production of neutralizing antibodies by the host. Nevertheless, the F protein represents the major target for antiviral drug development, especially in its prefusion form (preF), which has been shown to be highly superior at inducing neutralizing antibodies compared to its postfusion (postF) form. Human RSV exists as 2 antigenic subgroups, A and ...