key: cord-0008688-xaa9hxai authors: Anderson, Larry J.; Patriarca, Peter A.; Hierholzer, John C.; Noble, Gary R. title: Viral Respiratory Illnesses date: 2016-04-06 journal: Med Clin North Am DOI: 10.1016/s0025-7125(16)31164-6 sha: 5cd52ab29832a610de4d5453e4b33a97790861a5 doc_id: 8688 cord_uid: xaa9hxai nan Influenza Viruses The influenza viruses comprise three types, A, B, and C viruses, plus subtypes and strains within the types. These enveloped viruses contain single-stranded RNA, have a diameter of 80 to 100 nIU, and belong to the family Orthomyxoviridae. 46 Influenza viruses in diagnostic specimens lose infectivity within several days at room temperature but maintain infectivity at 4°C for up to one week. 3 Influenza is the only infectious disease that is consistently associated with significant increases in national mortality during epidemics. Infection with influenza viruses may be asymptonlatic (up to 50 per cent of infected individuals) or cause symptoms ranging from the common cold to fatal pneumonia. 43 , 44, 188 The severity of illness partly depends on the levels of pre-existing antibody to the infecting strains, age of the individual, and presence of chronic underlying disease. H2 , 120 Infection confers long-term strain-specific immunity, but the frequent changes in surface antigens of the influenza viruses result in life-long susceptibility to additional infections. Minor changes in the hemagglutinin (H) or neuraminidase (N) antigens of influenza A or B may be associated with epidemics, and major changes in the H or N antigens of influenza A lead to worldwide pandemics. Currently, influenza A (H3N2) viruses are the most important influenza viruses from both a clinical and epidemiologic standpoint. They infect persons in all age groups and have been associated with excess mortality in seven of nine periods of epidemic activity in the United States since eIuerging in 1968. 12 ,13,162 Influenza A (H1N1) virus has caused illness primarily among children, adolescents, and young adults following its reemergence in 1977 162 and has not been associated with excess 111ortality. Influenza B viruses tend to cause epidemics at 2-to 3-year intervals and primarily affect young persons, although the elderly may also experience illnesses; excess mortality was observed during the 1979-80 influenza season. 164 Influenza C viruses have been associated only with mild, sporadically occurring illness . 148 Small-particle aerosol is believed to be the most common Iuode of transmission of the influenza viruses. 1 The incubation period varies from 18 to 72 hours. Diagnosis of influenza is often based solely on a consistent clinical picture and presence of an influenza epidemic in the community. Infection can be most reliably confirmed by viral isolation in primary monkey kidney cells or embryonated hen's eggs, although FA staining of respiratory~spec imens can detect 80 to 90 per cent of those infections confirmed by isolation. 63 Influenza infection can also be detected in most instances by a rise in type-or subtype-specific antibodies. 46 Four serotypes and two subtypes of parainfluenza, types 1, 2, 3, 4a, and 4b, have been identified. These enveloped viruses have a diameter of 150 to 200 nm, contain a single strand of RNA, and belong to the family Paramyxoviridae. 20 Parainfluenza viruses lose infectivity at room temperature within several days and can maintain infectivity for as long as one week at 4°C.37, 38 Parainfluenza viruses are probably second only to rhi- The influenza viruses comprise three types, A, B, and C viruses, plus subtypes and strains within the types. These enveloped viruses contain single-stranded RNA, have a diameter of 80 to 100 nm, and belong to the family Orthomyxoviridae. 46 Influenza viruses in diagnostic specimens lose infectivity within several days at room temperature but maintain infectivity at 4° C for up to one week. 3 Influenza is the only infectious disease that is consistently associated with significant increases in national mortality during epidemics. Infection with influenza viruses may be asymptomatic (up to 50 per cent of infected individuals) or cause symptoms ranging from the common cold to fatal pneumonia. 43, 44, 188 The severity of illness partly depends on the levels of pre-existing antibody to the infecting strains, age of the individual, and presence of chronic underlying disease, 112, 120 Infection confers long-term strain-specific immunity, but the frequent changes in surface antigens of the influenza viruses result in life-long susceptibility to additional infections, Minor changes in the hemagglutinin (H) or neuraminidase (N) antigens of influenza A or B may be associated with epidemics, and major changes in the HorN antigens of influenza A lead to worldwide pandemics, Currently, influenza A (H3N2) viruses are the most important influenza viruses from both a clinical and epidemiologic standpoint. They infect persons in all age groups and have been associated with excess mortality in seven of nine periods of epidemic activity in the United States since emerging in 1968. 12 ,13,162 Influenza A (HINl) virus has caused illness primarily among children, adolescents, and young adults following its reemergence in 1977 162 and has not been associated with excess mortality. Influenza B viruses tend to cause epidemics at 2-to 3-year intervals and primarily affect young persons, although the elderly may also experience illnesses; excess mortality was observed during the 1979--80 influenza season. 164 Influenza C viruses have been associated only with mild, sporadically occurring illness. 148 Small-particle aerosol is believed to be the most common mode of transmission of the influenza viruses,1 The incubation period varies from 18 to 72 hours. Diagnosis of influenza is often based solely on a consistent clinical picture and presence of an influenza epidemic in the community, Infection can be most reliably confirmed by viral isolation in primary monkey kidney cells or embryonated hen's eggs, although FA staining of respiratory 'specimens can detect 80 to 90 per cent of those infections confirmed by isulation. 63 Influenza infection can also be detected in most instances by a rise in typeor subtype-specific antibodies. 46 Four serotypes and two subtypes of parainfluenza, types 1, 2, 3, 4a, and 4b, have been identified. These enveloped viruses have a diameter of 150 to 200 nm, contain a single strand of RNA, and belong to the family Paramyxoviridae. 20 Parainfluenza viruses lose infectivity at room temperature within several days and can maintain infectivity for as long as one week at 4° C.37,38 Parainfluenza viruses are probably second only to rhi-noviruses as a cause of respiratory illnesses in humans. 28, 71, 1.50 The spectrum and epidelniology of disease varies with the age of the population and the serotype. Only respiratory syncytial virus is more common than parainfluenza 3 as a capse of pneumonia and bronchiolitis in children under 2 years of age; parainfluenza 3 virus may be isolated throughout the year, but peaks of illness often occur in the fall and spring. 26, 64, 70, 150 Parainfluenza virus types 1 and 2, which are the leading cause of croup in children and a significant cause of childhood pneumonia, produce a peak incidence of infection at 2 to 6 years of age and occur primarily in epidemics. 58, 70, 71,109 Parainfluenza 4 is less frequently isolated, but serologic studies suggest it is a common infection, apparently causing mild or asymptomatic infections. 65, 122 Most persons have been infected with the parainfluenza viruses by age 5 and then have recurrent infections throughout life. Reinfections in adults usually cause a mild upper respiratory tract infection but can also cause more severe illness, including pneumonia. 22, 51, 150, 156, 203 The rate of reinfection decreases as the titer of serum neutralizing antibody increases. Protection from reinfection appears to be better correlated with antibody in nasal secretions than with antibody in serum. 22 , 193 The mode of transmission of parainfluenza virus has not been well studied, although transmission appears to be by direct person-to-person and/or droplet aerosol spread. 15S, 201 The incubation period ranges from 2 to 7 days, and virus can be isolated for up to 7 days or longer after onset of illness. 22, 60 FA, RIA, and ELISA tests are capable of detecting viral antigens in 75 to 95 per cent of respiratory secretions which yielded virus by isolation with few false-positive results. 63 , ISO Isolation in the clinical setting is complicated by the fact that the most sensitive cell line, primary rhesus monkey kidney, is not generally available. Serologic diagnosis of parainfluenza viral infections is hampered by heterologous antibody responses among the four types and with mumps virus, and by inconsistent homologous antibody responses. 20 Over 100 different serotypes of rhinovirus have been identified so far. Rhinoviruses are small, 20 to 30 nm in diameter, contain single-stranded RNA, are nonenveloped, and belong to the family Picornaviridae. 91 They are relatively stable viruses and can survive as long as three days on dry environmental surfaces. 174 Rhinoviruses are believed to be the most common respiratory pathogen of man, causing primarily mild upper respiratory symptoms, such as the common cold, but also causing lower respiratory tract illness, including pneumonia, in adults and children. 67, 77, 109, 151, 170 Approximately 75 per cent of infections are symptomatic. In temperate climates, rhinovirus infections occur throughout the year, with peaks in the fall and spring. During these peak seasons, multiple types of rhinoviruses may be simultaneously present in a community. 93 Higher numbered types and untypable rhinoviruses appear to be becoming more common than the lower numbered types, suggesting that there is antigenic drift among rhinoviruses. 56 Reinfection, as demonstrated by infection in the presence of type-specific serum neutralizing antibody, also occurs. The rate of reinfection, however, decreases with increasing noviruses as a cause of respiratory illnesses in humans. 28, 71, 1.50 The spectrum and epidemiology of disease varies with the age of the population and the serotype, Only respiratory syncytial virus is more common than parainfluenza 3 as a ca:use of pneumonia and bronchiolitis in children under 2 years of age; parainfluenza 3 virus may be isolated throughout the year, but peaks of illness often occur in the fall and spring. 26, 64, 70, 150 Parainfluenza virus types 1 and 2, which are the leading cause of croup in children and a significant cause of childhood pneumonia, produce a peak incidence of infection at 2 to 6 years of age and occur primarily in epidemics. 58, 70, 71, 109 Parainfluenza 4 is less frequently isolated, but serologic studies suggest it is a common infection, apparently causing mild or asymptomatic infections. 65, 122 Most persons have been infected with the parainfluenza viruses by age 5 and then have recurrent infections throughout life. Reinfections in adults usually cause a mild upper respiratory tract infection but can also cause more severe illness, including pneumonia. 22, 51, 150, 156, 203 The rate of reinfection decreases as the titer of serum neutralizing antibody increases. Protection from reinfection appears to be better correlated with antibody in nasal secretions than with antibody in serum. 22 , 193 The mode of transmission of parainfluenza virus has not been well studied, although transmission appears to be by direct person-to-person and/or droplet aerosol spread. 15B , 201 The incubation period ranges from 2 to 7 days, and virus can be isolated for up to 7 days or longer after onset of illness. 22, 60 FA, RIA, and ELISA tests are capable of detecting viral antigens in 75 to 95 per cent of respiratory secretions which yielded virus by isolation with few false-positive results. 63 , 180 Isolation in the clinical setting is complicated by the fact that the most sensitive cell line, primary rhesus monkey kidney, is not generally available. Serologic diagnosis of parainfluenza viral infections is hampered by heterologous antibody responses among the four types and with mumps virus, and by inconsistent homologous antibody responses. 20 Over 100 different serotypes of rhinovirus have been identified so far. Rhinoviruses are small, 20 to 30 nm in diameter, contain single-stranded RNA, are nonenveloped, and belong to the family Picornaviridae. 91 They are relatively stable viruses and can survive as long as three days on dry environmental surfaces. 174 Rhinoviruses are believed to be the most common respiratory pathogen of man, causing primarily mild upper respiratory symptoms, such as the common cold, but also causing lower respiratory tract illness, including pneumonia, in adults and children. 67, 77, 109, 151, 170 Approximately 75 per cent of infections are symptomatic. In temperate climates, rhinovirus infections occur throughout the year, with peaks in the fall and spring. During these peak seasons, multiple types of rhinoviruses may be simultaneously present in a community. 93 Higher numbered types and untypable rhinoviruses appear to be becoming more common than the lower numbered types, suggesting that there is antigenic drift among rhinoviruses. 56 Reinfection, as demonstrated by infection in the presence of type-specific serum neutralizing antibody, also occurs. The rate of reinfection, however, decreases with increasing titers of neutralizing antibody. 45, 97 Antigenic drift, reinfection, and the numerous serotypes may all contribute to the frequency of rhinovirus infections. Rhinoviruses are readily transmitted by autoinoculation with hands contaminated by direct person-to-person contact or by fomites. 79, 98 The most efficient site of inoculation is the nasal mucosa or conjunctiva. 8, 32 The incubation period is one to three days, and virus can be most readily isolated for four to six days and sometimes up to four weeks after onset. 45 , 56, 77 Identifying rhinovirus infections can be difficult. Because of the numerous serologic types, neither testing for antibody rises in serum nor for presence of antigen in respiratory secretions is presently practical. Isolation of rhinoviruses can also be difficult since they may grow poorly even in normally sensitive cell lines. 29 Respiratory Syncytial Virus Although several strains of respiratory syncytial virus (RSV) are known, 27, 102 strain differences have not yet been shown to have epidemiologic or clinical significance. 5 RSV is an enveloped virus with a diameter of 120 to 200 nm, contains single-stranded RNA, and belongs to the family Paramyxoviridae. 169 It is a labile virus; the titer of RSV drops by about 100fold within 2 days at room temperature and lOO-fold within 4 to 6 days at 4°C. 90 RSV is the most important cause of lower respiratory tract disease-pneumonia and bronchiolitis-in children under 2 years of age worldwide and is the only respiratory virus other than influenza that causes epidemics each year. These epidemics occur from late fall to spring and last from 2 to 5 months. 68, 123, 157 The role that host immune responses play in the pathogenesis of RSV disease is unclear. RSV is unique among viral diseases in its ability to cause serious illness among infants despite the presence of maternal neutralizing antibody.140 Reinfection with RSV occurs throughout life. In older children and adults, serum neutralizing antibody does not prevent but may ameliorate the illness. 96 , 168 Antibody in respiratory secretions may play a larger role in preventing infection. 117, 145 In adults, RSV usually causes a mild upper respiratory tract infection although it can also produce more severe illness, including pneumonia, especially in the elderly. 17, 85, 88, 136 RSV is transmitted by direct person-to-person spread and/or by'droplet aerosol spread and fomites. 82, 84 Symptoms occur about four to five days after initial infection, and virus can usually be isolated from the respiratory tract for three to five days or longer. Isolation of RSV can be accomplished in most virology laboratories. ELISA and FA tests for RSV antigens in respiratory specimens have been shown to be sensitive (85 to 90 per cent compared with isolation), specific, and practical. 63, 141 Infection can also be demonstrated by a rise in serum antibody titer by several different tests .169 Other Viruses That Cause Respiratory Illness Many viruses can cause respiratory illness alone or as part of other syndromes. Herpes simplex, especially type 1, and Epstein-Barr virus (EBV) are significant causes of pharyngitis; rubella, rubeola, and varicella can cause symptoms of an upper respiratory tract infection before onset of their typical rashes; and mumps can cause an upper respiratory tract infec-1014 L. J. ANDERSON, P. A. PATRIARCA, J. C. HIERJIOLZER AND C. R. NOBLE titers of neutralizing antibody.45. 97 Antigenic drift, reinfection, and the numerous serotypes may all contribute to the frequency of rhinovirus infections. Rhinoviruses are readily transmitted by auto inoculation with hands contaminated by direct person-ta-person contact or by fomites.'9, 98 The most efficient site of inoculation is the nasal mucosa or conjunctiva. 8 , 32 The incubation period is one to three days, and virus can be most readily isolated for four to six days and sometimes up to four weeks after onset. 45 . , 56, 77 Identifying rhinovirus infections can be difficult. Because of the numerous serologic types, neither testing for antibody rises in serum nor for presence of antigen in respiratory secretions is presently practical. Isolation of rhinoviruses can also be difficult since they may grow poorly even in normally sensitive celllines. 29 Although several strains of respiratory syncytial virus (RSV) are known, 27, 102 strain differences have not yet been shown to have epidemiologic or clinical significance. s RSV is an enveloped virus with a diameter of 120 to 200 nm, contains single-stranded RNA, and belongs to the family Paramyxoviridae.l 69 It is a labile virus; the titer of RSV drops by about 100fold within 2 days at room temperature and WO-fold within 4 to 6 days at 4° C. 90 RSV is the most important cause of lower respiratory tract disease-pneumonia and bronchiolitis-in children under 2 years of age worldwide and is the only respiratory virus other than influenza that causes epidemics each year. These epidemics occur from late fall to spring and last from 2 to 5 months. 68. 123, 157 The role that host immune responses play in the pathogenesis of RSV disease is unclear. RSV is unique among viral diseases in its ability to cause serious illness among infants despite the presence of maternal neutralizing antibody. 140 Reinfection with RSV occurs throughout life. In older children and adults, serum neutralizing antibody does not prevent but may ameliorate the illness. 96 . 168 Antibody in respiratory secretions may play a larger role in preventing infection.l 17 , 145 In adults, RSV usually causes a mild upper respiratory tract infection although it can also produce more severe illness, including pneumonia, especially in the elderly .17, 85, 88, 136 RSV is transmitted by direct person-to-person spread and/or by droplet aerosol spread and fomites. 82 , 84 Symptoms occur about four to five days after initial infection, and virus can usually be isolated from the respiratory tract for three to five days or longer. Isolation of RSV can be accomplished in most virology laboratories. ELISA and FA tests for RSV antigens in respiratory specimens have been shown to be sensitive (85 to 90 per cent compared with isolation), specific, and practical. 63, 141 Infection can also be demonstrated by a rise in serum antibody titer by several different tests, 169 Other Viruses That Cause Respiratory Illness Many viruses can cause respiratory illness alone or as part of other syndromes. Herpes simplex, especially type 1, and Epstein-Barr virus (EBV) are significant causes of pharyngitis; rubella, rubeola, and varicella can cause symptoms of an upper respiratory tract infection before onset of their typical rashes; and mumps can cause an upper respiratory tract infec-tion with or without the more typical parotitis. BK virus, a nonenveloped, double-stranded DNA virus in the family Papovaviridae, has recently been associated with respiratory illness. Infection of the respiratory tract with BK virus is common, and BK virus may cause 4 to 8 per cent of all acute respiratory disease. 73 Virtually all of the 67 enterovirus types, including polioviruses, coxsackie A and B viruses, echoviruses, and enterovirus 68-71, can cause respiratory tract illness (i. e., upper respiratory tract infection, pharyngitis, pneumonia, and acute respiratory disease in military recruits). 58, 74, 104, 127, 153, 154, 161, 171, 179 Enterovirus infections occur most commonly in children during the summer and fall months, with about 50 per cent of these infections being symptomatic. The viral respiratory syndromes are artificial categories taken from a continuum of illness ranging from asymptomatic infection to life-threatening pneumonia. Although artificial, these categories do provide a convenient way to discuss the causative agents and the general epidemiologic features of viral respiratory disease from a clinical perspective. Viral upper respiratory tract illness (URI), or the common cold, is probably the most common human infection and is a major cause of morbidity, visits to physicians, and time lost from work in the United States. 39 , 152, 159 URI is characterized by nasal discharge, nasal obstruction, sneezing, sore throat, and cough with or without fever. The illness usually lasts 5 to 7 days but can persist for several weeks or longer. The most common complications of viral URI are sinusitis and otitis media, which were estimated to occur in 0.5 to 1.9 per cent, respectively, of family members in one study. 39 In temperate climates, the prime' season for URI begins in late summer and early fall and continues into late spring. The season consists of (1) sequential outbreaks of infections caused by different viruses such as respiratory syncytial virus, influenza viruses, coronaviruses, and rhinoviruses; and (2) endemic infections with other viruses such as adenoviruses and parainfluenza 3 virus. Thus, at any given time the virus likely to be responsible for this syndrome varies greatly. The most commonly identified agents of URI among adults are rhinoviruses, followed by coronaviruses ( Table 2) . These viruses may also cause a significant portion of the URI of unknown etiology since they are more difficult to identify than some of the other viruses. Infection with rhinoviruses and coronaviruses is relatively less common in children, and infection with respiratory syncytial virus, parainfluenza viruses, and adenoviruses is more common. 24 , 31,109,118 Although pharyngitis is often part of other symptom complexes, such as the common cold or influenza syndrome, it can be caused by a different VIRAL RESPIHATORY ILLNESSES 1015 tion with or without the more typical parotitis. BK virus, a non enveloped, double-stranded DNA virus in the family Papovaviridae, has recently been associated with respiratory illness. Infection of the respiratory tract with BK virus is common, and BK virus may cause 4 to 8 per cent of all acute respiratory disease. 73 Virtually all of the 67 enterovirus types, including polioviruses, coxsackie A and B viruses, echoviruses, and enterovirus 68-71, can cause respiratory tract illness (i. e., upper respiratory tract infection, pharyngitis, pneumonia, and acute respiratory disease in military recruits).58. 74. 104, 127. 153, 154, 161, 171, 179 Enterovirus infections occur most commonly in children during the summer and fall months, with about 50 per cent of these infections being symptomatic. The viral respiratory syndromes are artificial categories taken from a continuum of illness ranging from asymptomatic infection to life-threatening pneumonia. Although artificial, these categories do provide a convenient way to discuss the causative agents and the general epidemiologic features of viral respiratory disease from a clinical perspective. Viral upper respiratory tract illness (URI), or the common cold, is probably the most common human infection and is a major cause of morbidity, visits to physicians, and time lost from work in the United States. 39 , 152, 159 URI is characterized by nasal discharge, nasal obstruction, sneezing, sore throat, and cough with or without fever. The illness usually lasts 5 to 7 days but can persist for several weeks or longer. The most common complications of viral URI are sinusitis and otitis media, which were estimated to occur in 0.5 to 1.9 per cent, respectively, of family members in one studv. 39 In temperate cli~ates, the prime' season for URI begins in late summer and early fall and continues into late spring. The season consists of (1) sequential outbreaks of infections caused by different viruses such as respiratory syncytial virus, influenza viruses, coronaviruses, and rhinoviruses; and (2) endemic infections with other viruses such as adenoviruses and parainfluenza 3 virus. Thus, at any given time the virus likely to be responsible for this syndrome varies greatly. The most commonly identified agents of URI among adults are rhinoviruses, followed by coronaviruses ( Table 2) . These viruses may also cause a significant portion of the URI of unknown etiology since they are more difficult to identify than some of the other viruses. Infection with rhinoviruses and coronaviruses is relatively less common in children, and infection with respiratory syncytial virus, parainfluenza viruses, and adenoviruses is more common. 24. 31. 109, 118 Pharyngitis Although pharyngitis is often part of other symptom complexes, such as the common cold or influenza syndrome, it can be caused by a different group of etiologic agents (see Table 2 ). Although the usual clinical features of the pharyngitis and the accompanying symptoms are different among the agents, the overlap in the clinical picture makes it impossible to determine the causative agent on clinical grounds alone. However, certain symptom complexes are likely to be viral: pharyngitis with vesicles, pharyngitis with rhinorrhea and nasal obstruction, and pharyngitis with conjunctivitis. In temperate climates, the peak season for pharyngitis coincides with that for URI. Influenza syndrome is characterized by the abrupt onset of fever, headache, severe myalgias, malaise, and prostration. 42, 44,162 These lnanifestations typically resolve within one to five days although cough, nasal congestion, and sore throat may then become more prominent. Cough and lassitude can persist for up to two weeks, even in uncomplicated cases, and most affected individuals recover spontaneously or with symptomatic therapy. Lower respiratory tract complications may occur in up to 10 per cent of patients,61 particularly in the elderly and in those with certain chronic disorders. Other complications, including myositis with myoglubinuria,144 myocarditis, 165 encephalitis,143 and Reye's syndrome,30 rarely occur with influenza viral infection. Influenza viruses are the most common cause of the influenza syndrome in civilian populations, although adenoviruses have been a major cause in military training camps. 50, 204 Other respiratory viruses, including coronavirus,126 have also been implicated in the influenza syndrome (see Table 2 ). Symptoms of tracheobronchitis (cough and expectoration) without pneumonia are commonly associated with viral respiratory infections, especially with influenza and parainfluenza viruses, respiratory syncytial vi- group of etiologic agents (see Table 2 ). Although the usual clinical features of the pharyngitis and the accompanying symptoms are different among the agents, the overlap in the clinical picture makes it impossible to determine the causative agent on clinical grounds alone. However, certain symptom complexes are likely to be viral: pharyngitis with vesicles, pharyngitis with rhinorrhea and nasal obstruction, and pharyngitis with conjunctivitis. In temperate climates, the peak season for pharyngitis coincides with that for URI. Influenza syndrome is characterized by the abrupt onset of fever, headache, severe myalgias, malaise, and prostration. 42, 44. 162 These manifestations typically resolve within one to five days although cough, nasal congestion, and sore throat may then become more prominent. Cough and lassitude can persist for up to two weeks, even in uncomplicated cases, and most affected individuals recover spontaneously or with symptomatic therapy. Lower respiratory tract complications may occur in up to 10 per cent of patients,61 particularly in the elderly and in those with certain chronic disorders. Other complications, including myositis with myoglubinuria,144 myocarditis, 165 encephalitis, 143 and Reye's syndrome, 30 rarely occur with influenza viral infection. Influenza viruses are the most common cause of the influenza syndrome in civilian populations, although adenoviruses have been a major cause in military training camps. 50, 204 Other respiratory viruses, including coronavirus,126 have also been implicated in the influenza syndrome (see Table 2 ). Symptoms of tracheobronchitis (cough and expectoration) without pneumonia are commonly associated with viral respiratory infections, especially with influenza and parainfluenza viruses, respiratory syncytial vi-rus, and adenovirus. 151, 189 Some persons with viral respiratory infections appear to be at increased risk of bronchitis. Smokers, for exalnple, may have an increased frequency and duration of coughing after rhinovirus and influenza infections, 78, 115 and patients with asthma and chronic bronchitis may experience exacerbations of their illnesses with viral respiratory infections. 138, 147, 191 Associated signs and symptoms, such as fever, rhinorrhea, myalgias, and pharyngitis, are usually present during the first three to six days of the illness, while cough and expectoration may last for several additional weeks. Acute bronchitis most commonly occurs during the viral respiratory season (fall, winter, and spring) and is usually caused by respiratory viruses or Mycoplasma pneumonia. Large-scale investigations during the past two decades suggest that viruses are relatively uncommon causes of pneumonia in adults, accounting for 25 to 50 per cent of nonbacterial pneumonias and only 12 per cent of all radiologically proven pneumonias. 41 , 52, 53,156,190 All of the respiratory viruses except coronaviruses have been implicated in community-acquired viral pneumonia, 17, 67, 136, 156, 203 but only influenza virus has been established as a common cause. 43 , 44, 175 Primary influenza pneumonia has been observed with both A and B virus types and can be a severe or relatively mild illness. 42, 44 Severe primary influenza pneumonia has been reported most commonly in elderly patients, individuals with chronic lung and heart diseases, and, in some epidemics, in women during the late stages of pregnancy,61, 133, 175, 182 but this type of pneumonia has also been detected in patients with no underlying predisposition. It is characterized by a rapid and relentless progression of respiratory distress with diffuse alveolar and interstitial infiltrates. Most patients die despite intensive supportive care. Mild influenza pneumonia most commonly occurs in younger patients 44 , 175 and is characterized by persistent cough, no respiratory distress, and sparse segmental infiltrates. These patients usually recover :completely. Secondary bacterial pneumonia and mixed viral and bacterial pneumonia accompany influenza infection more frequently than does primary influenza pneumonia. 7, 44, 133 The elderly and patients with certain chronic underlying disorders are at highest risk. 49, 112 Secondary bacterial pneumonia usually presents with recrudescence of fever and productive cough 5 to 14 days after the onset of influenza syndrome, and a chest roentgenogram shows an area of consolidation. Streptococcus pneumoniae, Staphylococcus aureus, and Hemophilus injluenzae are the most COlnmon pathogens. 7 ,183 With the advent of specific antiviral chemotherapy and increased awareness of nosocomial viral infections, the diagnosis of viral infections is becoming increasingly important. Diagnostic tests available to the clinician include serologic and antigen detection tests and viral isolation. Serologic testing has the advantage that serum specimens are generally easier to rus, and adenovirus. 151, 189 Some persons with viral respiratory infections appear to be at increased risk of bronchitis, Smokers, for example, may have an increased frequency and duration of coughing after rhinovirus and influenza infedions,78, 115 and patients with asthma and chronic bronchitis may experience exacerbations of their illnesses with viral respiratory infections . 138. 147. 191 Associated signs and symptoms, such as fever, rhinorrhea, myalgias, and pharyngitis, are usually present during the first three to six days of the illness, while cough and expectoration may last for several additional weeks. Acute bronchitis most commonly occurs during the viral respiratory season (fall, winter, and spring) and is usually caused by respiratory viruses or Mycoplasma pneumonia. Primary influenza pneumonia has been observed with both A and B virus types and can be a severe or relatively mild illness. 42 , 44 Severe primary influenza pneumonia has been reported most commonly in elderly patients, individuals with chronic lung and heart diseases, and, in some epidemics, in women during the late stages of pregnancy,61. 133, 175, 182 but this type of pneumonia has also been detected in patients with no underlying predisposition. It is characterized by a rapid and relentless progression of respiratory distress with diffuse alveolar and interstitial infiltrates. Most patients die despite intensive supportive care. Mild influenza pneumonia most commonly occurs in younger patients 44 , 175 and is characterized by persistent cough, no respiratory distress, and sparse segmental infiltrates. These patients usually recover completely. Secondary bacterial pneumonia and mixed viral and bacterial pneumonia accompany influenza infection more frequently than does primary influenza pneumonia. 7 , 44.133 The elderly and patients with certain chronic underlying disorders are at highest risk. 49, 112 Secondary bacterial pneumonia usually presents with recrudescence of fever and productive cough 5 to 14 days after the onset of influenza syndrome, and a chest roentgenogram shows an area of consolidation. Streptococcus pneumoniae, Staphylococcus aureus, and Hemophilus inJluenzae are the most common pathogens. 7, 183 With the advent of specific antiviral chemotherapy and increased awareness of nosocomial viral infections, the diagnosis of viral infections is becoming increasingly important. Diagnostic tests available to the clinician include serologic and antigen detection tests and viral isolation. Serologic testing has the advantage that serum specimens are generally easier to handle and transport, but this testing requires both acute and convalescent sera for comparison of antibody titers. Consequently, results are usually not available when clinically useful. No IgM tests for the rapid diagnosis of the respiratory viruses have yet been developed for general use. Serologic testing is also hampered by inconsistent antibody response after reinfection and the unavailability of screening tests for rhinoviruses and coronaviruses. A major advantage of rapid antigen detection tests for clinical specimens is that they can be completed in one to two days, while results are still clinically useful. As with serologic testing, however, screening tests are not available for rhinoviruses and coronaviruses. Viral isolation, on the other hand, does not require specific tests for a particular virus, though some may not be detected if the appropriate cell culture is not used, and some, such as coronavirus, are almost never isolated. Generally, viral isolation is more sensitive than antigen detection but takes longer and is more expensive. Using any of these tests effectively requires that specimens be collected at the appropriate time, handled correctly, and results interpreted in light of the sensitivity and specificity of the particular test. 25 For detecting changes in antibody titer, an acute-phase serum should be drawn as soon as possible after the onset of illness, preferably within three to four days, and a convalescent-serum two to four weeks later. For antigen detection tests and viral isolation, the specimen should be collected as soon as possible after the onset of illness, preferably within three to four days. For both viral isolation and antigen detection, a nasopharyngeal aspirate or wash is preferable to a nasopharyngeal or throat swab. For identifying RSV, one study showed nearly a 3-fold increase in isolation rate with a nasopharyngeal wash cOlnpared with a nasopharyngeal swab. 81 Isolation of most respiratory viruses from respiratory secretions generally provides an etiologic diagnosis, although care is needed in interpreting the significance of adenovirus and herpesvirus isolation since shedding may be prolonged. For all tests the sensitivity and specificity depend on the skill of the person performing the test, especially for FA, and the quality of the reagents. Thus, the results from one laboratory may be quite different froln those of another, and the clinician should be aware of the sensitivity and specificity of the tests as performed in the laboratory he or she uses. Diagnosis of viral respiratory infections is likely to increasingly rely on rapid detection tests for clinical specimens. For antigen detection, monoclonal antibodies are likely to be commonly used as reagents since they can provide sensitivity and specificity comparable to that of animal antiserum without variability in its quality. Tests for detecting viral DNA or other virus-specific components in clinical specimens are also being developed and may further improve our ability to detect viral respiratory infections. 200, 206 Nosocomial viral infections are increasingly recognized as an important problem. Studies have shown that they cause significant morbidity, prolongation of hospitalization, and dea.th, especially among infants and handle and transport, but this testing requires both acute and convalescent sera for comparison of antibody titers. Consequently, results are usually not available when clinically useful. No IgM tests for the rapid diagnosis of the respiratory viruses have yet been developed for general use. Serologic testing is also hampered by inconsistent antibody response after reinfection and the unavailability of screening tests for rhinoviruses and coronaviruses. A major advantage of rapid antigen detection tests for clinical specimens is that they can be completed in one to two days, while results are still clinically useful. As with serologic testing, however, screening tests are not available for rhinoviruses and coronaviruses. Viral isolation, on the other hand, does not require specific tests for a particular virus, though some may not be detected if the appropriate cell culture is not used, and some, such as coronavirus, are almost never isolated. Generally, viral isolation is more sensitive than antigen detection but takes longer and is more expensive. U sing any of these tests effectively requires that specimens be collected at the appropriate time, handled correctly, and results interpreted in light of the sensitivity and specificity of the particular test. 25 For detecting changes in antibody titer, an acute-phase serum should be drawn as soon as possible after the onset of illness, preferably within three to four days, and a convalescent-serum two to four weeks later. For antigen detection tests and viral isolation, the specimen should be collected as soon as possible after the onset of illness, preferably within three to four days. For both viral isolation and antigen detection, a nasopharyngeal aspirate or wash is preferable to a nasopharyngeal or throat swab. For identifYing RSV, one study showed nearly a 3-fold increase in isolation rate with a nasopharyngeal wash compared with a nasopharyngeal swab. 81 Isolation of most respiratory viruses from respiratory secretions generally provides an etiologic diagnosis, although care is needed in interpreting the significance of adenovirus and herpesvirus isolation since shedding may be prolonged. For all tests the sensitivity and specificity depend on the skill of the person performing the test, especially for FA, and the quality of the reagents. Thus, the results from one laboratory may be quite different from those of another, and the clinician should be aware of the sensitivity and specificity of the tests as performed in the laboratory he or she uses. Diagnosis of viral respiratory infections is likely to increasingly rely on rapid detection tests for clinical specimens. For antigen detection, monoclonal antibodies are likely to be commonly used as reagents since they can provide sensitivity and specificity comparable to that of animal antiserum without variability in its quality. Tests for detecting viral DNA or other virus-specific components in clinical specimens are also being developed and may further improve our ability to detect viral respiratory infections. 200, 206 Nosocomial viral infections are increasingly recognized as an important problem. Studies have shown that they cause significant morbidity, prolongation of hospitalization, and death, especially among infants and children. 198 Respiratory viruses are probably the most important of the viral nosocomial pathogens and often occur as part of community outbreaks. The epidemiology of outbreaks of nosocomial viral respiratory infections is just beginning to be understood, and guidelines for their prevention and control are being developed. 195, 197 Influenza has been recognized as a nosocomial pathogen for some time and has been well documented to cause outbreaks in nursing homes and hospitals. 72, 89, 199 It spreads in an explosive fashion, presumably by aerosol, and once introduced into the hospital is very difficult to control. Thus, although the effectiveness of preventive measures has not been well studied, measures such as vaccination of hospital and nursing home staff and restriction of visitors with influenza like-illness are most likely to be effective if initiated when influenza is in the community but before a nosocomial outbreak occurs. Once a confirmed outbreak occurs, amantadine prophylaxis can be given to unvaccinated patients and staff, and patients with influenza can be isolated. 108 , 195 Respiratory syncytial virus has been shown to be a major nosocomial pathogen in pediatric hospitals, causing significant morbidity and death in children under the age of 2, especially in those with compromised cardiac function. 83, 134 It has also been associated with outbreaks among the elderly in chronic-care facilities, causing significant morbidity and some deaths. 17, 66, 136 Spread of this pathogen requires close contact, which may occur through infected hospital staff and fomites. 82, 83 Respiratory syncytial virus does not spread as rapidly as influenza, and thus its spread in the hospital is more likely to be preventable. Separating infected from uninfected patients, cohorting staff to ill patients, strict hand washing, and use of gowns by staff may prevent spread of an outbreak. 86 The parainfluenza viruses have been implicated in outbreaks in pediatric hospitals 62 , 158, 201 and among the elderly in chronic-care facilities . 16 The spread and, therefore, the prevention and control of parainfluenza viruses are presumed to be similar to those for respiratory syncytial virus. Adenoviruses have been implicated in nosocomial outbreaks among children and adults, often spreading from patients to staff. 15, 99, 130, 172 They usually occur sporadically and not as part of recognized community outbreaks. To prevent and control outbreaks of adenovirus infections, infected and uninfected patients should probably be separated, staff members should wear gowns and gloves, and strict hand washing should be enforced. 197 Coronaviruses and rhinoviruses are not known to be important nosocomial pathogens, but both have been implicated in nosocomial outbreaks of respiratory illness. 176, 196 PREVENTION, CONTROL, AND TREATMENT OF VIRAL RESPIRATORY INFECTIONS Prevention, control, and treatment of viral respiratory infections have met with limited success. Vaccines and chemotherapeutic agents for general use have been developed only for influenza. Another approach to prevention and control of these viruses is to interrupt their transmission. VIRAL RESPIRATORY ILLNESSES 1019 children. 19B Respiratory viruses are probably the most important of the viral nosocomial pathogens and often occur as part of community outbreaks. The epidemiology of outbreaks of nosocomial viral respiratory infections is just beginning to be understood, and guidelines for their prevention and control are being developed. 195, 197 Influenza has been recognized as a nosocomial pathogen for some time and has been well documented to cause outbreaks in nursing homes and hospitals, 72, 89, 199 It spreads in an explosive fashion, presumably by aerosol, and once introduced into the hospital is very difficult to control. Thus, although the effectiveness of preventive measures has not been well studied, measures such as vaccination of hospital and nursing home staff and restriction of visitors with influenza like-illness are most likely to be effective if initiated when influenza is in the community but before a nosocomial outbreak occurs. Once a confirmed outbreak occurs, amantadine prophylaxis can be given to unvaccinated patients and staff, and patients with influenza can be isolated. lOB, 195 Respiratory syncytial virus has been shown to be a major nosocomial pathogen in pediatric hospitals, causing significant morbidity and death in children under the age of 2, especially in those with compromised cardiac function. 83 134 It has also been associated with outbreaks among the elderly in chronic-care facilities, causing significant morbidity and some deaths. l7 , 66, 136 Spread of this pathogen requires close contact, which may occur through infected hospital staff and fomites. 82, 83 Respiratory syncytial virus does not spread as rapidly as influenza, and thus its spread in the hospital is more likely to be preventable. Separating infected from uninfected patients, cohorting staff to ill patients, strict hand washing, and use of gowns by staff may prevent spread of an outbreak. 86 The parainfluenza viruses have been implicated in outbreaks in pediatric hospitals 62 , 158, 201 and among the elderly in chronic-care facilities . 16 The spread and, therefore, the prevention and control of parainfluenza viruses are presumed to be similar to those for respiratory syncytial virus. Adenoviruses have been implicated in nosocomial outbreaks among children and adults, often spreading from patients to staff. 15, 99, 130, 172 They usually occur sporadically and not as part of recognized community outbreaks. To prevent and control outbreaks of adenovirus infections, infected and uninfected patients should probably be separated, staff members should wear gowns and gloves, and strict hand washing should be enforced. 197 Coronaviruses and rhinoviruses are not known to be important nosocomial pathogens, but both have been implicated in nosocomial outbreaks of respiratory illness. 176, 196 PREVENTION, CONTROL, AND TREATMENT OF VIRAL RESPIRATORY INFECTIONS Prevention, control, and treatment of viral respiratory infections have met with limited success. Vaccines and chemotherapeutic agents for general use have been developed only for influenza. Another approach to prevention and control of these viruses is to interrupt their transmission. Studies on the use of disinfectants, as applied to the hands or environlnental surfaces, have shown either equivocal results or the technique is not practical for widespread use. 76 , 80 Studies of nosocomial respiratory syncytial virus and adenovirus infections suggest that interruption of transmission is possible by separating infected from uninfected patients and by the use of gowns and gloves and strict handwashing by staff members. 86, 130 Additional studies on methods to interrupt transmission of the respiratory viruses, especially in the hospital, are needed. In the United States, only vaccines for influenza and adenovirus infection have been licensed. The licensed influenza vaccine consists of inactivated virus, and use of the vaccine has been strongly recommended only for individuals at greatest risk of serious pulmonary complications or death following influenza. Such individuals include the elderly and those with certain chronic underlying diseases, including acquired or congenital heart disease, chronic obstructive pulmonary disease, renal impairment, diabetes mellitus, severe anemia, and conditions that compromise the immune system. Unfortunately, only about 20 per cent of some 48 million people in high-risk groups are vaccinated each year. 18 Unlike other vaccines, the component strains must be updated frequently to keep pace with antigenic changes in influenza viruses. The influenza vaccines stimulate an increase in antibody titer in 50 to 90 per cent of recipients, often associated with comparable degrees of protection from infection. 2, 14, 121, 142, 163, 173 Live attenuated oral vaccines for adenoviruses 4, 7, and 21 are being used in military personnel and have been very effective in reducing acute respiratory disease in recruits. 47, 192 Experimental vaccines have been developed for a number of the respiratory viruses. Considerable research has been devoted to the development of live attenuated influenza vaccines that are administered intranasally. 4, 121 It is hoped that by simulating natural infection, live vaccines will be more effective than inactivated ones. The vaccines tested to-date, however, have often failed to induce an adequate antibody response inseropositive individuals, and some have been associated with a high rate of adverse reactions, particularly in seronegative individuals. The many serotypes of rhinoviruses have thus far precluded the development of vaccines for these viruses. Since natural infection with respiratory syncytial virus, parainfluenza virus, and coronavirus induces shortterm immunity, and reinfections occur throughout life, the prospects for vaccines against these viruses are less than promising. However, infections caused by respiratory syncytial virus and parainfluenza virus are major health problems in infants and young children worldwide, and considerable effort is being made to develop vaccines for this age group. 194 Inactivated vaccines for respiratory syncytial virus were found not to be protective and may have predisposed recipients to more severe illness during subsequent natural infection. 23 Live attenuated vaccines for respiratory syncytial virus are currently being evaluated for parenteral and intranasal administration. 6, 205 Thus far, none of these vaccines has been shown to be effective. Vaccines for the parainfluenza viruses are being developed. 194 1020 L. J. ANDERSON, P. A. PATRIARCA, J. C. HIERHOLZER AND G. R. NOBLE Studies on the use of disinfectants, as applied to the hands or environmental surfaces, have shown either equivocal results or the technique is not practical for widespread use. 76 . 80 Studies of nosocomial respiratory syncytial virus and adenovirus infections suggest that interruption of transmission is possible by separating infected from uninfected patients and by the use of gowns and gloves and strict handwashing by staff members. 86, 1.30 Additional studies on methods to interrupt transmission of the respiratory viruses, especially in the hospital, are needed. In the United States, only vaccines for influenza and adenovirus infection have been licensed. The licensed influenza vaccine consists of inactivated virus, and use of the vaccine has been strongly recommended only for individuals at greatest risk of serious pulmonary complications or death following influenza. Such individuals include the elderly and those with certain chronic underlying diseases, including acquired or congenital heart disease, chronic obstructive pulmonary disease, renal impairment, diabetes mellitus, severe anemia, and conditions that compromise the immune system. Unfortunately, only about 20 per cent of some 48 million people in high-risk groups are vaccinated each year. 18 Unlike other vaccines, the component strains must be updated frequently to keep pace with antigenic changes in influenza viruses. The influenza vaccines stimulate an increase in antibody titer in 50 to 90 per cent of recipients, often associated with comparable degrees of protection from infection. 2, 14, 121, 142, 163, l7.3 Live attenuated oral vaccines for adenoviruses 4, 7, and 21 are being used in military personnel and have been very effective in reducing acute respiratory disease in recruits. 47 , 192 Experimental vaccines have been developed for a number of the respiratory viruses. Considerable research has been devoted to the development of live attenuated influenza vaccines that are administered intranasally. 4, 121 It is hoped that by simulating natural infection, live vaccines will be more effective than inactivated ones. The vaccines tested to' date, however, have often failed to induce an adequate antibody response in seropositive individuals, and some have been associated with a high rate of adverse reactions, particularly in seronegative individuals. The many serotypes of rhinoviruses have thus far precluded the development of vaccines for these viruses. Since natural infection with respiratory syncytial virus, parainfluenza virus, and coronavirus induces shortterm immunity, and reinfections occur throughout life, the prospects for vaccines against these viruses are less than promising. However, infections caused by respiratory syncytial virus and parainfluenza virus are major health problems in infants and young children worldwide, and considerable effort is being made to develop vaccines for this age group. 194 Inactivated vaccines for respiratory syncytial virus were found not to be protective and may have predisposed recipients to more severe illness during subsequent natural infection. 23 Live attenuated vaccines for respiratory syncytial virus are currently being evaluated for parenteral and intranasal administration. 6, 21J5 Thus far, none of these vaccines has been shown to be effective. Vaccines for the parainfluenza viruses are being developed. 194 The use of recolubinant technology, cloning, and peptide synthesis may in the future contribute to improved vaccines for respiratory viruses. 21, 113, 128 Chemotherapy Antiviral chemotherapy is available for the treatment and prophylaxis of influenza A infection. Amantadine hydrochloride (Symmetrel)* has been shown to be effective in both the treatment and prophylaxis of influenza A infections, probably by interfering with the penetration step of viral replication. 107, 160 When 200 mg per day of amantadine is begun within the first 24 to 48 hours of illness, the duration of uncomplicated illness and virus shedding is shortened and the extent of small-airway abnormalities is reduced. It is unknown whether amantadine is effective in treating primary influenza A pneumonia. When taken daily for the duration of an epidemic of influenza A (generally 6 to 8 weeks), amantadine has been shown to be 50 to 70 per cent effective in preventing infection 107 but should not be considered a substitute for vaccination.I 12 Amantadine is primarily excreted unmetabolized in the urine. Thus, it may accumulate when renal function is impaired. 107 Side effects, the most common of which include difficulty in concentration, confusion, hallucinations, anxiety, insomnia, anorexia, and dyspepsia, occur in 10 to 33 per cent of adults. 160 Studies of several investigational antiviral drugs have yielded promising results. Rimantadine, an analog of amantadine, appears to be as effective in the treatment and prophylaxis of influenza as amantadine. 40 Ribavirin, a synthetic ribonucleoside, has exhibited in vitro and in vivo activity against a number of viruses including influenza A and B and respiratory syncytial virus. Ill, 166 In clinical studies of infections caused by influenza A and B and respiratory syncytial virus, it has achieved promising results when administered as an aerosol by lace mask. 87, 124, 137 Interferon administered by nasal spray before and after challenge with rhinovirus appeared to delay the onset and decrease the severity of symptoms of infection in volunteers. 181 Other investigational drugs, including isoprinosine for prophylaxis and treatment of infections due to influenza A (H3N2),132 enviroxime for rhinoviruses,129 and vitamin C for the common cold, 19, 48 have so far not been shown to be effective. Viral respiratory illness is likely to continue to be a fact of life for some time, with symptomatic therapy the only intervention available to the clinician in most instances. However, for the patient with more serious illness, the patient with compromised immune, cardiac, or respiratory systems, and the hospitalized patient, developments in the 1980s and 1990s are likely to permit effective intervention. For the seriously ill and the *Use of trade names is for identification only and does not imply endorsement by the Public Health Service or by the United States Department of Health and Human Services. The use of recombinant technology, cloning, and peptide synthesis may in the future contribute to improved vaccines for respiratory viruses.21, 113, 128 Antiviral chemotherapy is available for the treatment and prophylaxis of influenza A infection. Amantadine hydrochloride (Symmetrel)* has been shown to be effective in both the treatment and prophylaxis of influenza A infections, probably by interfering with the penetration step of viral replication. 107 , 160 When 200 mg per day of amantadine is begun within the first 24 to 48 hours of illness, the duration of uncomplicated illness and virus shedding is shortened and the extent of small-airway abnormalities is reduced. It is unknown whether amantadine is effective in treating primary influenza A pneumonia. When taken daily for the duration of an epidemic of influenza A (generally 6 to 8 weeks), amantadine has been shown to be 50 to 70 per cent effective in preventing infection lO7 but should not be considered a substitute for vaccination. m Amantadine is primarily excreted unmetabolized in the urine. Thus, it may accumulate when renal function is impaired. 107 Side effects, the most common of which include difficulty in concentration, confusion, hallucinations, anxiety, insomnia, anorexia, and dyspepsia, occur in 10 to 33 per cent of adults. 160 Studies of several investigational antiviral drugs have yielded promising results. Rimantadine, an analog of amantadine, appears to be as effec-ti~e in the treatment and prophylaxis of influenza as amantadine. 4o Ribavirin, a synthetic ribonucleoside, has exhibited in vitro and in vivo activity against a number of viruses including influenza A and B and respiratory syncytial virus. Ill. 166 In clinical studies of infections caused by influenza A and B and respiratory syncytial virus, it has achieved promising results when administered as an aerosol by lace mask. 87, 124, 137 Interferon administered by nasal spray before and after challenge with rhinovirus appeared to delay the onset and decrease the severity of symptoms of infection in volunteers.lsl Other investigational drugs, including isoprinosine for prophylaxis and treatment of infections due to influenza A (H3N2), l.32 enviroxime for rhinoviruses,129 and vitamin C for the common cold,19, 48 have so far not been shown to be effective. Viral respiratory illness is likely to continue to be a fact of life for some time, with symptomatic therapy the only intervention available to the clinician in most instances. However, for the patient with more serious illness, the patient with compromised immune, cardiac, or respiratory systems, and the hospitalized patient, developments in the 1980s and 1990s are likely to permit effective intervention. For the seriouslv ill and the *Use of trade names is for identification only and does not imply endorsement by the Public Health Service or by the United States Department of Health and Human Services. immunocompromised patient, diagnosis of a viral respiratory infection may permit the clinician to discontinue antibiotics and to initiate appropriate antiviral therapy. For the hospitalized patient, diagnosis of a viral respiratory infection may alert the medical staff to the possibility of a nosocomial outbreak and prompt them to initiate appropriate control measures. The diagnosis, control and treatment of viral respiratory infections will become more than just a scientific curiosity-they will be an important part of the clinician's armamentarium. immunocompromised patient, diagnosis of a viral respiratory infection may permit the clinician to discontinue antibiotics and to initiate appropriate antiviral therapy. For the hospitalized patient, diagnosis of a viral respiratory infection may alert the medical staff to the possibility of a nosocomial outbreak and prompt them to initiate appropriate control measures. The diagnosis, control and treatment of viral respiratory infections will become more than just a scientific curiosity-they will be an important part of the clinician's armamentarium. 18 Human influenza resulting from aerosol inhalation Influenza vaccination of elderly persons. Reduction in pneumonia and influenza hospitalizations and deaths Maintenance of viability and comparison of identification methods of influenza and other respiratory viruses of humans Research into the immunization of humans against influenza by means of living viruses Repeated infections with respiratory syncytial virus Parenteral administration of live respiratory syncytial virus vaccine: Results of a field trial Pneumonia and Hong Kong influenza: A prospective study of the 1968-1969 epidemic Inoculation of human volunteers with a strain of virus from a common cold Epidemic of adenovirus type 7 acute conjunctivitis in swimlners Adenovirus hepatitis in an immunosuppressed adult patient Centers for Disease Control: A study of the impact of the 1978-1979 National Immunization Program on specific physician groups Centers for Disease Control: Influenza vaccine efficacy in nursing home outbreaks reported during 1981-1982 Centers for Disease Control: Nosocomial outbreak of pharyngoconjunctival fever due to adenovirus, Type 4-New York Centers for Disease Control: Parainfluenza outbreaks in extended-care facilities-U nited States Human influenza resulting from aerosol inhalation Influenza vaccination of elderly persons. Reduction in pneumonia and influenza hospitalizations and deaths Maintenance of viability and comparison of identification methods of influenza and other respiratory viruses of humans Research into the immunization of humans against influenza by means of living viruses Repeated infections with respiratory syncytial virus Parenteral administration of live respiratory syncytial virus vaccine: Results of a field trial Pneumonia and Hong Kong influenza: A prospective study of the 1968-1969 epidemic Inoculation of human volunteers with a strain of virus from a common cold Epidemic of adenovirus type 7 acute conjunctivitis in swimmers Adenovirus hepatitis in an immunosuppressed adult patient Centers for Disease Control: A study of the impact of the 1978-1979 National Immunization Program on specific physician groups Centers for Disease Control: Influenza Surveillance Heport No. 92 Centers for Disease Control: Influenza Surveillance Heport ]\;0. 93 Centers for Disease Control: Influenza vaccine efficacy in nursing home outbreaks reported during 1981-1982 Centers for Disease Control: Nosocomial outbreak of pharyngoconjunctival fever due to adenovirus, Type 4-New York Centers for Disease Control: Parainfluenza outbreaks in extended-care facilities-United States Effects of ascorbic acid on the common cold: An evaluation of the evidence Diagnostic Procedures for Viral Strategy for development of respiratory and gastrointestinal tract viral vaccines in the 1980's Natural history of parainfluenza infection Respiratory syncytial virus Comparative biology and ecology of human virus and mycoplasma respiratory pathogens Cumulative techniques and procedures in clinical microbiology, 15: Laboratory diagnosis of viral infections. Washington Parainfluenza virus infections An antigenic analysis of respiratory syncytial virus isolates by a plaque reduction neutralization test The Seattle virus watch: VI. Observations of infections with and illness due to parainfluenza, mumps and respiratory syncytial viruses and mycoplasma pneumoniae K: Demonstration of dual rhinovirus infection in humans by isolation of different serotypes in human heteroploid (He La) and human diploid fibroblast cell cultures A nationwide outbreak of Reye's syndrome. Its epidemiologic relationship to influenza B Clinical Syndromes in children caused by respiratory infection Effect of route of inoculation on experimental respiratory viral disease in volunteers and evidence for airborne transmission Pharyngoconjunctival fever caused by adenovirus type 4: Report of a swimming pool-related outbreak with recovery of virus from pool water Adenovirus type 8 keratoconjunctivitis in the United States. Ill. Epidemiologic, clinical, and microbiologic features Parainfluenza type 3 in a transplant unit Adenovirus 37: Identification and characterization of a medically important new adenovirus type of subgroup D Certain biological characteristics of myxovirus para-influenza 3 Characteristics of parainfluenza 1 (HA-2) virus. Ill. Antigenic relationships, growth, interaction with erythrocytes, and physical properties Illness in the home: A study of 25,000 illnesses in a group of Cleveland families A controlled trial of amantadine and rimantadine in the prophylaxis of influenza A infection Etiologies and characteristic features of pneumonias in a municipal hospital. An1 Influenza in man Viral respiratory diseases Influenza virus Quantitative rhinovirus shedding patterns in volunteers Influenza viruses An analysis of hospitalizations for acute respiratory disease in recruits immunized with adenovirus type 4 and type 7 vaccines Ascorbic acid and the common cold: Evaluation of its efficacy and toxicity Immunization against influenza: Rationale and recommendations Clinical syndromes in adults caused by respiratory infection Acute pharyngitis and tonsillitis in University of Wisconsin students Bacteria, viruses and mycoplasn1as in acute pneumonia in adults A study of the combined role of viruses, mycoplasmas and bacteria in adult pneumonia Role of adenovirus type 11 in hemorrhagic cystitis secondary to immunosuppression Fatal adenovirus type 7 pneun10nia in an adult The Seattle virus watch: V. Epidemiologic observations of rhinovirus infections, 1965-1969, in families with young children The Seattle virus watch: 11. Objectives, study population and its observation, data processing and summary of illnesses. An1 Incidence and etiology of pneumonia, croup and bronchiolitis in pre-school children belonging to a prepaid medical care group over a four-year period Adenoviruses Patterns of shedding of myxoviruses and paramyxoviruses in children Influenza, 1959. The story of an epidemic Virus cross-infection in paediatric wards Rapid Virus Diagnosis: Application of hnl11UnO-fluorescence Observations on clinical and in1-munofluorescent diagnosis of parainfluenza virus infections The isolation of parainfluenza 4 subtypes A and B in England and serologic studies of their prevalence Outbreak of respiratory syncytial virus infection in the elderly Etiologies and characteristic features of pneumonias in a municipal hospital Influenza in man Viral respiratory diseases Influenza virus Quantitative rhinovirus shedcling patterns in volunteers Influenza viruses An analysis of hospitalizations for acute respiratory disease in recruits immunized with aclenovirllS type 4 ancl type 7 vaccines Ascorbic acicl and the common colcl: Evaluation ofits efficacy ancl toxicity Immunization against influenza: Rationale and recommenclations Clinical synclromes in aclults causecl by respiratory infection Acute pharyngitis and tonsillitis in University of Wise onsin stuclents Bacteria, viruses and mycoplasmas in acute pneumonia in adults A study of the combined role of viruses, mycoplasmas and bacteria in aclult pneumonia Role of adenovirus type 11 in hemorrhagic cystitis seconclary to immunosuppression Fatal aclenovirus type 7 pneumonia in an adult The Seattle virus watch: V. Epidemiologic observations of rhinovirus infections, 1965-1969, in families with young chilclren The Seattle virus watch: n. Objectives, stucly population and its observation, clata processing and summary of illnesses Incidence ancl etiology of pneumonia, croup and bronchiolitis in pre-school children belonging to a prepaid meclical care group over a four-year period Viral Infections of Humans: Epiclemiology ancl Control. Eclition Patterns of sheclding of myxoviruses and paramyxoviruses in children Influenza, 1959. The story of an epiclemic Virus cross-infection in paediatric warcls Rapid Virus Diagnosis: Application of Immunofluorescence. Eclition 2 Observations on clinical and immunofluorescent cliagnosis of para influenza virus infections The isolation of parainfluenza 4 subtypes A ancl B in England ancl serologic stuclies of their prevalence Outbreak of respiratory syncytial virus infection in the elderly Atypical pneul1lonia in young nlen with rhinovirus infections Epidemiology of acute lower respiratory disease in children Acute respiratory disease of university students with special reference to the etiologic role of herpesvirus hominis Epidemiologic patterns of acute lower respiratory disease of children in a pediatric group practice Viral Infections of Humans: Epidemiology and Control Impact of influenza A in a nursing home The role of BK virus in acute respiratory tract disease and the presence of BKV DNA in tonsils Enteroviruses in human disease Epidemic keratoconjunctivitis: A community outbreak of mixed adenovirus type 8 and type 19 infection Transmission of experimental rhinovirus infection by contaminated surfaces Rhinovirus infections in an industrial population: 1. The occurrence of illness Rhinovirus infections in an industrial population. I!. Characteristics of illness and antibody response Hand-to-hand transmission of rhinovirus colds Interruption of experimental rhinovirus transmission Clinically useful method for the isolation of respiratory syncytial virus Modes of transmission of respiratory syncytial virus Nosocomial respiratory syncytial virus infections Possible transmission by fomites of respiratory syncytial virus Respiratory syncytial virus infections within families Control of nosocomial respiratory syncytial viral infections Ribavirin treatment of experimental respiratory syncytial viral infection: A controlled double-blind study in young adults Respiratory syncytial virus infection in adults: Clinical, virologic, and serial pulmonary function studies An outbreak of influenza B in an elderly population Survival of the respiratory syncytial virus during storage under various conditions Diagnostic Procedures for Viral, Rickettsial and Chlamydia! Infections. Edition 5. Washington VIRAL RESPIRATORY ILLNESSES 1025 Atypical pneumonia in young mcn with rhinovirus infections Epidemiology of acute lower respiratory disease in children Acute rcspiratory disease of university students with special reference to the etiologic role of herpesvirus hominis Epidemiologic patterns of acute lower respiratory disease of children in a pediatric group practice Viral Infections of Humans: Epidemiology and Control Impact of influenza A in a nursing home The role of BK virus in acute respiratory tract disease and the presence of BKV DNA in tonsils Enteroviruses in human disease Epidemic keratoconjunctivitis: A community outbreak of mixed adenovirus type 8 and type 19 infection Transmission of experimental rhinovirus infection by contaminated surfaces Rhinovirus infections in an industrial population: 1. The occurrence of illness Rhinovirus infections in an industrial population. n. Characteristics of illness and antibody response Hand-to-hand transmission ofrhinovirus colds Interruption of experimental rhinovirus transmission Clinically useful method for the isolation of respiratory syncytial virus Modes of transmission of respiratory syncytial virus Nosocomial respiratory syncytial virus infections Possible transmission by fomites of respiratory syncytial virus Respiratory syncytial virus infections within families Control of nosocomial respiratory syncytial viral infections Ribavirin treatment of experimental respiratory syncytial viral infection: A controlled double-blind study in young adults Respiratory syncytial virus infection in adults: Clinical, virologic, and serial pulmonary function studies An outbreak of influenza B in an elderly population Survival of the respiratory syncytial virus during storage under various conditions Diagnostic Procedures for Viral, Rickettsial and Chlamydial Infections. Edition 5. Washington Virologic studies of acute respiratory disease in young adults: V. Coronavirus 229E infections during six years of surveillance Virologic studies of acute respiratory disease in young adults: IV. Virus isolations during four years of surveillance Enzyme immunoassay for direct detection of influenza type A and adenovirus antigens in clinical specimens Isolation of adenovirus type 19 from the male and female genital tracts Respiratory-syncytial-virus infections, reinfections and immunity: A prospective, longitudinal study in young children Relation between naturally acquired inlmunity and infectiVity of two rhinoviruses in volunteers Transmission of rhinovirus colds by self inoculation Adenovirus type 3 pneumonia causing lung damage in childhood New human adenovirus isolated from a renal transplant recipient: Description and characterization of candidate adenovirus type 34 Acute hemorrhagic conjunctivitis Croup and pneumonia in human infants associated with a new strain of respiratory syncytial virus The RNA and proteins of human coronaviruses Prospective study of a Inixed coxsackie virus B3 and B4 outbreak of upper respiratory illness in a children's home Occurrence of respiratory illness due to an atypical strain of adenovirus type 11 during a large outbreak in Spanish military recruits Generalized viral illness caused by an intermediate strain of adenovirus (211H21 + 35) Antiviral agents Control of influenza in the hospital Respiratory viral infection in childhood. A survey in general practice, Roehampton 1967-1972 OC43 strain-related coronavirus antibodies in different age groups In vivo inhibition of respiratory syncytial virus by ribavirin Immunization Practices Advisory Committee: Influenza vaccines Antigenic activity of a synthetic peptide comprising the "loop" region of influenza virus hemagglutinin Viruses causing common respiratory infection in man. IV. Reoviruses and adenoviruses Cigarette smoking as a risk factor for epidemic A(H1N1) influenza in young men Virologie studies of acute respiratory disease in young adults: V. Coronavirus 229E infections during six years of surveillance Virologic studies of acute respiratory disease in young adults: IV. Virus isolations during four years of surveillance Enzyme immunoassay for direct detection of influenza type A and adenovirus antigens in clinical specimens Isolation of adenovirus type 19 from the male and female genital tracts Respiratory-syncytial-virus infections, re infections and immunity: A prospective, longitudinal study in young children Relation between naturally acquired immunity and infectivity of two rhinoviruses in volunteers Transmission of rhinovirus colds by self inoculation Adenovirus type 3 pneumonia causing lung damage in childhood New human adenovirus isolated from a renal transplant recipient: Description and characterization of candidate adenovirus type 34 Acute hemorrhagic conjunctivitis Croup and pneumonia in human infants associated with a new strain of respiratory syncytial virus The HNA and proteins of human coronaviruses Prospective study of a mixed coxsackie virus B3 and B4 outbreak of upper respiratory illness in a children's home Occurrence of respiratory illness due to an atypical strain of adenovirus type 11 during a large outbreak in Spanish military recruits Generalized viral illness caused by an intermediate strain of adenovirus (211H21 +35) Antiviral agents Control of influenza in the hospital Hespiratory viral infection in childhood. A survey in general practice, Roehampton 1967-1972 OC43 strain-related coronavirus antibodies in different age groups In vivo inhibition of respiratory syncytial virus by ribavirin Immunization Practices Advisorv Committee: Influenza vaccines Antigenic activity of a synthetic peptide comprising the "loop" region of influenza virus hemagglutinin Viruses causing common respiratory infection in man. IV. Heoviruses and adenoviruses Cigarette smoking as a risk factor for epidemic A(H1N1) influenza in young men Adenoviruses Secretory antibody response to respiratory syncytial virus infection Seroepidemiologic survey of coronavirus (strain OC43) related infections in a children's population Keratoconjunctivitis associated with adenovirus type 37: An extended outbreak in an ophthalmologist's office Specific immunity in influenza. Summary of influenza workshop Ill Influenza vaccines. Summary of influenza workshop V Antigenic characterization of parainfluenza 4A and 4B by the hemagglutination-inhibition test and distribution of HI antibody in human sera 1. Importance of the virus in different respiratory tract disease syndromes and temporal distribution of infection Ribavirin small-particle aerosol treatment of influenza Virological studies on gynecological patients Isolation of rhinoviruses and coronaviruses from 38 colds in adults Infections due to Coxsackie virus group A, type 9 The development of synthetic vaccines Topical enviroxime against rhinovirus infection Nosocomial conjunctivitis caused by adenovirus type 4 Fatal non-bacterial pneumonia associated with adenovirus type 4 Effect of isoprinosine against challenge with A(H3N2)/Hong Kong influenza virus in volunteers Studies on influence in the pandemic of 1957-1958. 11. Pulmonary complications of influenza Respiratory syncytial viral infection in infants with congenital heart disease An outbreak of adenovirus type 3 disease at a private recreation center swimming pool Concurrent respiratory syncytial virus and influenza A infections in the institutionalized elderly and chronically ill Ribavirin aerosol treatment of influenza B virus infection A study of infective and other factors in exacerbations of chronic bronchitis Coronaviruses: A comparative review Immunopathologic mechanisms in lower respiratory VIRAL RESPIRATORY ILLNESSES 1027 Adenoviruses Secretory antibody response to respiratory syncytial virus infection Seroepidemiologic survey of coronavirus (strain OC43) related infections in a children's population Keratoconjunctivitis associated with adenovirus type 37: An extended outbreak in an ophthalmologist's office Specific immunity in influenza. Summary of influenza workshop Ill Influenza vaccines. Summary of influenza workshop V Antigenic characterization of parainfluenza 4A and 4B by the hemagglutination-inhibition test and distribution of HI antibody in human sera 1. Importance of the virus in different respiratory tract disease syndromes and temporal distribution of infection Ribavirin small-particle aerosol treatment of influenza Virological studies on gynecological patients Isolation of rhinoviruses and coronaviruses from 38 colds in adults Infections due to Coxsackie virus group A, type 9 The development of synthetic vaccines Topical enviroxime against rhinovirus infection Nosocomial conjunctivitis caused by adenovirus type 4 Fatal non-bacterial pneumonia associated with adenovirus type 4 Effect of isoprinosine against challenge with A(H3N2)/Hong Kong influenza virus in volunteers Studies on influence in the pandemic of 1957-1958. ll. Pulmonary complications of influenza Respiratory syncytial viral infection in infants with congenital heart disease An outbreak of adenovirus type 3 disease at a private recreation center swimming pool Concurrent respiratory syncytial virus and influenza A infections in the institutionalized elderly and chronically ill Ribavirin aerosol treatment of influenza B virus infection A study of infective and other factors in exacerbations of chronic bronchitis Coronaviruses: A comparative review Immunopathologic mechanisms in lower respiratory tract disease of infants due to respiratory syncytial virus Enzyme-linked in1munosor-bent assay for detection of respiratory syncytial virus infection: Application to clinical samples Antigenic drift and efficacy of influenza virus vaccines Influenza encephalitis Severe myositis during recovery from influenza Experimental respiratory syncytial virus infection of adults: Possible lnechanisms of resistance to infection and illness Comparison of direct immunofluorescent staining of clinical specimens for respiratory virus antigens with conventional isolation techniques Rhinovirus and influenza type A infections as precipitants of asthma Viruses associated with upper respiratory illnesses in adults Viral Infections of Humans: Epidemiology and Control The Tecumseh study of respiratory illness: V. Patterns of infection with the parainfluenzaviruses The Tecumseh study of respiratory illness: n. Patterns of occurrence of infection with respiratory pathogens Acute respiratory illness in an American community: The Tecumseh study Enteroviral disease in the United States, 1970-1979 Non-polio enterovirus disease in the United States, 1971-1975 A review of adenoviruses in the etiology of acute hemorrhagic cystitis The role of viruses, mycoplasmas and bacteria in acute pneumonia in civilian adults Viruses, Mycoplasma pneumoniae and bacteria associated with lower respiratory tract disease among infants Acquisition of parainfluenza 3 virus infection by hospitalized children. 1. Frequencies, rates, and temporal data Current estimates from health interview survey, United States-1981 Amantadine: Does it have a role in the prevention and treatment of influenza? A National Institutes of Health Consensus Development Conference Non-polio enterovirus activity in Wisconsin based on a 20-year experience in a diagnostic virology laboratory Epidemiological and clinical aspects of influenza Influenza vaccine (editorial) Morbidity and mortality associated with influenza B in the United States, 1979-1980 Enzyme-linked immunosorbent assay for detection of respiratory syncytial virus infection: Application to clinical samples Antigenic drift and efficacy of influenza virus vaccines Influenza encephalitis Severe myositis during recoverv from influenza Experimental respiratory syncytial virus infection of adults: Possible mechanisms of resistance to infection and illness Comparison of direct immunofluorescent staining of clinical specimens for respiratory virus antigens with conventional isolation techniques Rhinovirus and influenza type A infections as precipitants of asthma Viruses associated with upper respiratory illnesses in adults Viral Infections of Humans: Epidemiology and Control. Edition 2. J\'ew York The Tecumseh study of respiratory illness: V. Patterns of infection with the parainfluenzaviruses The Tecumseh study of respiratory illness: n. Patterns of occurrence of infection with respiratory pathogens Acute respiratory illness in an American community: The Tecumseh study Enteroviral disease in the United States Non-polio enterovirus disease in the United States, 1971-1975 A review of adenoviruses in the etiology of acute hemorrhagic cystitis The role of viruses, mycoplasmas and bacteria in acute pneumonia in civilian adults Viruses, Mycoplasma pneumoniae and bacteria associated with lower respiratory tract disease among infants Acquisition of parainfluenza.3 virus infection by hospitalized children. 1. Frequencies, rates, and temporal data Current estimates from health interview survey, United States-1981 Amantadine: Does it have a role in the prevention and treatment of influenza? A National Institutes of Health Consensus Development Conference Non-polio enterovirus activity in Wisconsin based on a 20-year experience in a diagnostic virology laboratory Epidemiological and clinical aspects of influenza Influenza vaccine (editorial) Morbidity and mortality associated with influenza B in the United States, 1979-1980 Clinicopathologic study of 33 fatal cases of Asian influenza Inhibition of the replication of influenza A and B viruses by a nucleoside analogue (ribavirin) Pan American Health Organization: Acute respiratory infections in children. Washington, D. C., Pan American Health Organization II. Infection and disease with respect to age, immunologic status, race and sex Respiratory syncytial virus Experiences in laboratory diagnosis of rhinovirus infections in routine medical practice Enteroviruses in Vermont, 1969-1978: An important cause of illness throughout the year Type 3 adenoviral pneumonia occurring in a respiratory intensive care unit Inactivated influenza virus vaccine An investigation of the possible transmission of rhinovirus colds through indirect contact Viral pneumonia Coronavirus infections of man associated with diseases other than the common cold Isolation of an adenovirus 32 strain from human brain in a case of subacute encephalitis The isolation of coxsackie group B viruses fron1 cases of respiratory illness Type-specific detection of parainfluenza viruses by enzyme immunoassay and radioimmunoassay in nasopharyngeal specimens of patients with acute respiratory disease Purified interferon as protection against rhinovirus infection Respiratory infection in pregnancy Bacterial pneumonia during the Hong Kong influenza epidemic of Weekly clinicopathological exercises (presentation of case 6-1979) Fatal disseminated adenovirus-ll pneumonia in an agammaglobulinemic patient Adenoviruses. Status of current knowledge New human adenovirus (candidate adenovirus type 35) causing fatal disseminated infection in a renal transplant recipient Twenty years of influenza epidemics A collaborative study of the aetiology of acute respiratory infections in Britain 1961-64: A report of the Medical VIRAL RESPIRATORY ILL~ESSES Clinicopathologic study of 33 Eltal cases of Asian influenza Inhibition of the replication of influenza A and B viruses by a nucleoside analogue (ribavirin) Pan American Health Organization: Acute respiratory infections in children. Washington, D. C., Pan American Health Organization Epidemiology of respiratory syncytial virus infection in \'ashington, D. c.: 11. Infection and disease with respect to age, immunologic status, race and sex Respiratory syncytial virus Experiences in laboratory diagnosis of rhinovirus infections in routine medical practice Enteroviruses in Vermont, 1969-1978: An important cause of illness throughout the year Type 3 adenoviral pneumonia occurring in a respiratory intensive care unit Inactivated influenza virus vaccine An investigation of the possible transmission of rhinovirus colds through indirect contact Viral pneumonia Coronavirus infections of man associated with diseases other than the common cold Isolation of an adenovirus 32 strain from human brain in a case of subacute encephalitis The isolation of coxsackie group B viruses from cases of respiratory illness Type-specific detection of parainfluenza viruses by enzyme immunoassay and radioimmunoassay in nasopharyngeal specimens of patients with acute respiratory disease Purified interferon as protection against rhinovirus infection Respiratory infection in pregnancy Bacterial pneumonia during the Hong Kong influenza epidemic of Weekly clinicopathological exercises (presentation of case 6-1979) Fatal disseminated adenovirus-11 pneumonia in an agammaglobulinemic patient Adenoviruses. Status of current knowledge New human adenovirus (candidate adenovirus type 35) causing fatal disseminated infection in a renal transplant recipient Twenty years of influenza epidemics A collaborative study of the aetiology of acute respiratory infections in Britain 1961-64: A report of the Medical Research Council working party on acute respiratory virus infections Adult pneuITIonia in a general hospital: Etiology and host risk factors Role of infection in chronic bronchitis Simultaneous adnlinistration of live, enteric-coated adenovirus types 4, 7, and 21 vaccines: Safety and immunogenicity Neutralizing activity in nasal secretions and serum in resistance of volunteers to parainfluenza virus type 2 Report of a workshop on respiratory syncytial virus and parainfluenza virus Nosocomial viral infections. 11. Guidelines for prevention and control of respiratory viruses, herpesviruses, and hepatitis viruses Concurrent outbreaks of rhinovirus and respiratory syncytial virus in an intensive care nursery: Epidemiology and associated risk factors Nosocomial viral infections. Ill. Guidelines for prevention and control of exanthematous viruses, gastroenteritis viruses, picornaviruses, and uncommonly seen viruses Nosocomial viral infections:' 1. Epidemiology and significance Nosocomial influenza B virus infection in the elderly Novel test for rapid viral diagnosis: Detection of adenovirus in nasopharyngeal mucous aspirates by means of nucleic-acid sandwich hybridisation Hospital-acquired viral respiratory illness on a pediatric ward Coronavirus infections in nlilitary recruits. Three-year study with coronavirus strains OC43 and 229E Parainfluenza pneumonia in adults Acute respiratory disease: Clinical and epidemiologic observations in military trainees Administration of highly attenuated, live respiratory syncytial virus vaccine to adults and children Enzyme immunoassays for the detection of infectious antigens in body flUids: Current limitations and future prospects Adenovirus infection in the immunocompromised patient Research Council working party on acute respiratory virus infections Adult pneumonia in a general hospital: Etiology and host risk factors Role of infection in chronic bronchitis Simllitalleous administration of live, enteric-coated adenovirus types 4, 7, and 21 vaccines: Safety and immunogenicity Neutralizing activity in nasal secretions and serum in resistance of volunteers to parainfluenza virus type 2 Report of a workshop on respiratory syncytial virus and parainfluenza virus Nosocomial viral infections. Il. Guidelines for prevention and control of respiratory viruses, herpesviruses, and hepatitis viruses Concurrent outbreaks of rhinovirus and respiratory syncytial virus in an intensive care nursery: Epidemiology and associated risk factors Nosocomial viral infections. Ill. Guidelines for prevention and control of exanthematous viruses, gastroenteritis viruses, picornaviruses, and uncommonly seen viruses Nosocomial viral infections: I. Epidemiology and significance Nosocomial influenza B virus infection in the elderly Novel test for rapid viral diagnosis: Detection of adenovirus in nasopharyngeal mncous aspirates by means of nucleic-acid sandwich hybridisation Hospital-acquired viral respiratory illness on a pediatric ward Coronavirus infections in military recruits. Three-year study with coronavirus strains OC43 and 229E Parainfluenza pneumonia in adults Acute respiratory disease: Clinical and epidemiologic observations in military trainees Administration of highly attenuated, live respiratory syncytial virus vaccine to adults and children Enzyme immunoassays for the detection of infectious antigens in body fluids: Current limitations and future prospects Adenovirus infection in the immunocompromised patient The authors thank Evelyn B. DuVal for her assistance in preparing this n1anuscript. The authors thank Evelyn B. DuVal for her assistance in preparing this manuscript.