RSV is an enveloped virus with a genome composed of a single negative strand of RNA. The virion has a diameter of 150 to 300 nm. The nucleocapsid, 12 to 15 nm in diameter, is smaller than that of the other members of the paramyxovirus family; thus, the virus has been placed in the separate genus Pneumovirus. Human metapneumovirus (HMPV) was described in 2001 (6). The virologic, epidemiologic, and clinical characteristics of this virus are similar to those of RSV (6, 7, 8, 9, 10, 11 and 12).

RSV is relatively quickly inactivated after exposure to different environmental conditions. In studies using partially purified virus, virus survival decreased as the temperature at which the virus was stored was increased over the range from 55°C to 65°C (13). Virus survival was best at a pH of 7.5 with decreasing infectivity as pH was raised or lowered. RSV is rapidly inactivated by ether, chloroform, and detergents (14,15). Studies of virus survival using nasal secretions from infected infants revealed that infectious virus could be recovered for approximately 0.5 hours on skin, 1 hour on porous surfaces, and 7 hours on nonporous surfaces (16).

Both RSV and HMPV have a single serotype based on neutralization with human sera but have two subgroups (17). The clinical and immunologic significance of these antigenic differences has not been clarified; however, the detection of different viral strains by monoclonal antibody testing and/or nucleic acid analysis is useful in epidemiologic studies (18, 19 and 20).

RSV infection is the most common cause of lower respiratory infection in young infants. Fifty percent to seventy percent of all infants are infected during the first year of life, and by the age of 4 virtually all infants have had at least one infection (21,22). Reinfection with RSV is common and, despite the nearly universal experience with this infection, the attack rate is approximately 40% for exposed individuals in all age groups (21,23). HMPV infection is also very common with most individuals infected in early childhood.

The seasonal occurrence of RSV infections is well defined. Epidemics of RSV occur annually in the winter or spring (24). These epidemics are consistently associated with increased hospital admissions for pediatric respiratory infection, although the severity of the epidemic varies from year to year. RSV is transmitted by contact with infected respiratory secretions. A study of RSV transmission found that close contact with an infected infant, when virus may be transmitted directly or by large-particle aerosols, or contact with virus-contaminated fomites could transmit infectious RSV to volunteer recipients (25). Transmission of virus by small-particle aerosols was not detected in this study. The role of environmental contamination in the transmission of RSV is not clear, although RSV can survive on environmental surfaces for hours (16) and can be recovered from the environment of infected infants (25). Infection with RSV requires that the virus reach the respiratory mucosa. Inoculation of infectious virus into either the nose or the eye is equally efficient for initiation of infection and much more efficient than oral inoculation (26). The incubation period of RSV infection is 2 to 8 days with an average of about 5 days (27, 28 and 29). Once virus infects the upper respiratory mucosa, it may spread to the lower respiratory tract. RSV infection is limited to the respiratory tract, and respiratory secretions are the only body fluids that contain infectious virus. Shedding of RSV can be detected for a few days before onset of symptoms and generally continues for approximately 1 week (30). Shedding is detected for >2 weeks in approximately 10% of patients.

Immunoprotection against RSV appears to be conferred by serum and secretory antibody (21,31,32). A role for cell-mediated immune responses in the termination of RSV infection is suggested by the observation that children with deficiencies of T-cell immunity have unusually severe infections and prolonged shedding of virus (33).

RSV infection may result in clinical illness involving any level of the respiratory tract. The most severe manifestations of RSV infection are bronchiolitis or pneumonia. The incidence of lower respiratory symptoms is greatest during primary infections in young infants (21,22). Both increasing age and recurrences of infection are associated with an increasing proportion of infections that are asymptomatic or limited to the upper respiratory tract. Hospitalization for RSV infection is generally due to lower respiratory tract infection or apnea. However, during the RSV season, many infants admitted to the hospital have an incidental, community-acquired, RSV infection. HMPV has a similar clinical presentation but generally produces milder illnesses than RSV (34,35).

The parainfluenza viruses are enveloped RNA viruses that are members of the genus Paramyxovirus in the family Paramyxoviridae. These viruses are susceptible to a variety of chemical disinfectants (36,37). There are four different serotypes of parainfluenza, types 1 to 4, which can be differentiated by antibody to complement-fixing and hemagglutinating antigens. No antigenic variation in these serotypes has been recognized over many years of observation.

Early studies of the parainfluenza viruses reported that both parainfluenza type 1 and type 3 were endemic with infections reported in virtually all months of the year (38). More recent data suggest that infection with parainfluenza type 1 occurs as a fall epidemic in 2-year cycles (39). Parainfluenza, type 2, is much less common and the epidemic peak is more variable. Infections with parainfluenza virus types 1 and 2 are most common in children between 6 months and 6 years of age. By 5 years of age, most children have been infected with both serotypes of virus (38).

In contrast to the behavior of serotypes 1 and 2, infection with serotype 3 occurs in biennial peaks that may be moderated somewhat in the years of high parainfluenza type 1 activity (39). Parainfluenza virus type 3 is a common cause of infection in young infants. A serologic survey reported that 60% of infants were seropositive by 1 year of age and 80% were positive by the time they were 4 years old (38). The actual incidence of infection may be somewhat higher because reinfection, which would not be detected by serology, occurs often in young infants (40). Parainfluenza type 3 often produces illness in the first 6 months of life despite the presence of maternal antibody. The peak incidence of illness is in the second year of life. Primary infections occurring in the second year of life are more likely to be associated with lower respiratory tract infection than those that occur earlier or later. Reinfections with parainfluenza type 3 occur commonly but are generally associated with mild upper respiratory illness.

The parainfluenza viruses have an apparent incubation period of 2 to 8 days (41,42). Viral shedding from the upper respiratory tract occurs 1 to 4 days before the onset of symptoms and continues for 7 to 10 days in most patients with primary infection (30). Some patients with primary infection continue to have intermittent shedding of virus for 3 to 4 weeks. The duration of shedding following reinfection is generally shorter than that after primary infection; however, reinfected patients occasionally shed virus for longer than 2 weeks (30). The mechanism of transmission of the parainfluenza viruses is not known; however, the route of spread is presumed to be by large droplets or direct person-to-person contact.

The serotype of the virus and the presence of preexisting homotypic antibody appear to affect the clinical manifestations of parainfluenza virus infection. Infection with parainfluenza type 1 is most commonly associated with a febrile upper respiratory infection. The most common lower respiratory tract manifestation of type 1 infection is croup. Parainfluenza type 2 is associated with similar clinical manifestations, although the illnesses are generally less severe. Preexisting nasal secretory antibody appears to offer some protection against infection (42). Parainfluenza virus type 3 is associated with disease at all levels of the respiratory tract and is not associated with a predominant clinical syndrome (39). This virus is second only to RSV as a cause of bronchiolitis and pneumonia in young infants.

The adenoviruses are nonenveloped viruses with a genome of double-stranded DNA. These viruses are not inactivated by ether or chloroform and are stable at temperatures of 4°C to 36°C and pH of 5 to 9. Adenovirus is inactivated by sodium dodecylsulfate, chlorine, ultraviolet (UV) radiation, or formalin. There are >40 distinct serotypes of adenovirus; types 1 to 7 are the most important in pediatric respiratory disease.

Adenovirus type 14 has recently emerged as a cause of respiratory disease especially in military recruits but is not yet a significant threat for hospital-acquired infection (43). Adenovirus infections are an important cause of illness in childhood (44). Antibody to serotypes 1 and 2 is detected in the serum of 60% to 80% of children by 5 years of age, and approximately 40% also have antibody to serotypes 3 and 5 (45,46). About one-half of the adenovirus infections in these infants are associated with illness. The peak incidence of adenovirus-related illness occurs between 6 months and 2 years of age (47), and adenovirus causes 5% to 10% of all febrile respiratory illnesses in children younger than 7 years (46,47). Adenovirus is a much less common cause of respiratory illness in older children or adults. Adenovirus infections are endemic and cause illness in all months of the year (24); an increased incidence of infection has been noted between December and July in some studies (45,46).

The fecal-oral route may be the most likely route of transmission of adenovirus between young children although transmission by aerosol can also occur. Transmission of infection has been documented in families following experimentally induced fecal excretion of adenovirus type 4 (48). During adenovirus infections, fecal excretion of virus occurs in >75% of children (46). Transmission of infection is relatively efficient; 46% to 67% of susceptible household and day care contacts were infected after exposure to adenovirus (46,47). The incubation period of adenovirus in children is not known. However, in adults challenged by the aerosol route, the incubation period was 6 to 13 days (49), and, in a hospital outbreak, the apparent incubation period was 2 to 18 days (50). A unique feature of adenovirus among the pediatric respiratory viruses is that intermittent shedding of the virus may continue for years after infection. Approximately one-half of adenovirus infections are associated with only a single day of virus shedding. One-fourth of the infections, however, result in intermittent shedding of virus for >3 months, and almost 10% continue to shed virus for >1 year (46). Homotypic antibody, whether actively acquired by previous infection or passively acquired by maternal transmission, is partially protective for both infection and illness.

The most common respiratory manifestation of adenovirus infection in young infants is a febrile upper respiratory syndrome (44,47,51,52). Although conjunctivitis is widely recognized as a manifestation of adenovirus infection, only 12% of outpatients (47) and 4% of hospitalized patients i have this finding. Hospitalized patients with adenovirus infection often have high and prolonged fevers (51,52).

The rhinoviruses are small, nonenveloped, single-stranded RNA viruses in the picornavirus family. The human rhinoviruses are stable at a pH of 6 to 8 and are not inactivated by chloroform, ether, or detergents (53, 54 and 55). These viruses are rapidly inactivated at a pH of 3 and by UV irradiation. Rhinovirus survives well under environmental conditions. Virus was recovered after 1 hour on porous surfaces, 3 hours on nonporous surfaces, and 3 hours on human skin (56). Other reports have suggested that virus may remain viable in the environment for several days (57). There are >100 distinct rhinovirus serotypes that all appear to have similar epidemiologic characteristics and produce a similar clinical syndrome.

In contrast to other viral respiratory pathogens of childhood, the incidence of rhinovirus infection varies little with age. Approximately two-thirds of children experience a rhinovirus infection each year (58,59); about 60% of these infections are associated with illness. Rhinoviruses cause illness in all months of the year, but there are distinct epidemic peaks of illness in the early fall and in the late spring (58, 59, 60 and 61).

The mechanism of transmission of rhinovirus has been studied extensively. In experimental models, rhinovirus is transmitted most efficiently by direct person-to-person contact (62), although transmission by large-particle aerosols has also been documented (62,63). A study of natural colds found that treatment of the hands with a virucidal compound prevented transmission of rhinovirus infection, suggesting that hand-to-hand transmission may be important in a natural setting (57). Once virus is transmitted, the incubation period is generally short, with onset of symptoms in 2 to 3 days, although, in a family setting, rhinovirus was cultured from 15% of specimens collected 7 to 10 days before the onset of symptoms (58). Rhinovirus is shed exclusively from the upper respiratory tract. Shedding is most efficient from nasal secretions, although lower titers of virus can be detected in saliva and pharyngeal secretions (64). Virus can also be recovered from the hands of a high proportion of infected volunteers (56). Shedding of virus from infected individuals continues for 2 to 3 weeks after the onset of illness (58,65). Homotypic serum neutralizing antibody correlates with resistance to rhinovirus infection (59,66,67). The characteristic clinical syndrome associated with rhinovirus infection is the common cold but rhinovirus is also an important cause of exacerbations of asthma. These infections are generally not associated with fever.