Virus infections and respiratory disease of childhood.

Respiratory disease has always been present amongst children, but the importance of viruses in its causation is a recent discovery. An historical approach shows the rapid development of our knowledge of the part played by viruses in the aetiology of respiratory infection. The three influenza viruses were the first of the respiratory viruses to be discovered: influenza A by Smith, Andrewes, and Laidlaw in 1933; influenza B independently by Francis and by Magill in 1940; and influenza C by Taylor in 1949. It was, however, the application of tissue culture techniques to virology by Enders, Weller, and Robbins in 1949 which opened the gate for a flood of new viruses. Members of the adenovirus group were found as latent infections of tonsils and adenoids by Rowe and his colleagues in 1953. A different member of this new group was associated with an outbreak of respiratory disease among military recruits (Hilleman and Werner, 1954). The next group to be discovered was parainfluenza viruses, pioneered by Chanock and his colleagues in the United States in 1958, and by Beale et al. in Canada in the same year. These viruses had originally been called the haemadsorption viruses because of their method of identification. Perhaps the most important find of all was the discovery and association of respiratory syncytial virus with severe respiratory disease in childhood, again by Chanock and his colleagues in 1961. This virus had previously been described in 1956 by Morris, Blount, and Savage as one which had caused a coryza in chimpanzees. The name respiratory syncytial virus (RSV) is descriptive of the appearance produced when it is inoculated on to the appropriate tissue cultures, and, as far more children were found to suffer from this virus than chimpanzees, the name was accordingly changed. This period also saw the isolation of the first members of the rhinovirus group by Tyrrell and his colleagues (1960), which now number well over 80 distinct antigenic types. The association of a number of miscellaneous members of the Coxsackie and echovirus groups with respiratory disease was also found at this time (Philipson, 1958; Heggie et al., 1960; Kendall, Cook, and Stone, 1960). The latest addition to the complex virus picture is a number of viruses similar to the avian bronchitis virus and mouse hepatitis virus (McIntosh, Becker, and Chanock, 1967) which are isolated in human organ culture. Bradburne, Bynoe, and Tyrrell (1967) showed that one of these viruses could cause cold-like illnesses in volunteers. The relation of this group to the fowl and murine viruses has still to be determined, but it appears that a new family of respiratory viruses capable of causing human disease has been discovered. A study of children's respiratory disease should start in the home. The late Sir James Spence initiated the great 1000 family study in Newcastle which has given a wealth of information about childhood disease, including respiratory infections (Miller et al., 1960). The investigation began with the study of 847 children observed from birth to 5 years and, between them, these had a total of 4147 respiratory illnesses. In addition, there were 8 fatal cases of pneumonia, all occurring within the first year of life. Unfortunately, at the time of the 1000 family study, virology was in its infancy and facilities were not available for the investigation of those viruses which were then known. Nevertheless, this survey gave the first insight into the extent of respiratory disease in the family and the importance of respiratory infection in relation to the whole of childhood disease. This is well illustrated in Fig. 1. Dingle, Badger, and Jordan (1964) initiated a 10-year study of civilian families in Cleveland, Ohio, in 1948, the emphasis being placed on the occurrence and behaviour of illness over a period of years. These workers believed that a family was the basic epidemiological unit, having the major influence on health and disease. Like the 1000 family study mentioned above, this investiga-