SYNOPSIS The pathological changes are described in 22 children with proven or suspected virus infection of the lower respiratory tract. Two main patterns of disease were found: acute bronchiolitis and interstitial pneumonia. Particular viruses were not specifically associated with particular histological changes. The prime importance of the respiratory syncytial virus (RSV) as a cause of disease and death in young infants is again shown. Structural lesions and clinical dysfunction correlate fairly well; in acute bronchiolitis the main lesion is epithelial necrosis when a dense plug is formed in the bronchiolar lumen leading to trapping air and other mechanical interference with ventilation: in interstitial pneumonia there is widespread inflammation and necrosis of lung parenchyma, and severe lesions of the bronchial and bronchiolar mucosa as well. The implications of these structural changes for clinical management are discussed. The possibility of a hypersensitivity reaction in the cot death syndrome is raised, mediated by a serum antibody-antigen-complement reaction.In 1967 3,000 children died in England and Wales from infection of the respiratory tract. They accounted for 27 % of all deaths in children between the ages of 1 month and 15 years. Seventy-five per cent were infants under the age of 1 year, and 46 % died at home (General Register Office, 1967, and personal communication). The corresponding figures for our community, the northern region of England, were 204 deaths of which 80 % were infants. In Newcastle, of every 100 acute infective illnesses in the first five years oflife, 60 affect the respiratory tract, and 17 are either bronchitis, bronchiolitis, or pneumonia. A large and challenging task, therefore, still faces those concerned with the clinical management of these illnesses and a clearer understanding of their aetiology and pathogenesis is urgently needed.Except in proven bacterial infections aetiology

11 the severity of the clinical symptoms could not be adequately explained by valvular regurgitation, of which there was little evidence on examination of the heart. Blood cultures usually remained sterile, presumably because of inappropriate antibiotic treatment or the limited infectiveness of the organisms present, or both.A striking feature in three patients (cases 1, 2, and 4) was the acute, severe, and rapidly resolving but recurrent episodes of pulmonary oedema. Possibly these were caused by sudden blocking of the orifice by -vegetation-this was indeed shown echocardiographically in one patient (case 4). Other patients (cases 3 and 5 and those reported by Reeve et all and Matula et al2) had more progressive pulmonary oedema, suggesting increasing mitral stenosis. In our experience both types of pulmonary oedema are uncommon in patients with isolated mitral valve regurgitation during bacterial endocarditis.Those of our patients who did not have mitral valve replacement (cases 2, 4, and 5) and the patient of Reeve and his colleagues' had a sudden cardiac arrest. Mitral valve vegetations cause obstruction just as catastrophic as an atrial tumour or a ball thrombus, and hence once the doctor suspects mitral valve obstruction he should confirm the diagnosis promptly and ensure that the patient is rapidly operated on.Accurate diagnosis is vital. Right heart catheterisation showed a raised pulmonary wedge pressure without a striking V wave, but was nevertheless of little value in assessing the severity of the haemodynamic disturbance: pressures may be very high because of rheumatic valve disease (case 4) Journal, 1978, 1, 11-14 Summary and conclusions Thirty-five children known to have had respiratory syncytial virus bronchiolitis in infancy were examined at the age of 8 and their respiratory function tested. The results were compared with those in 35 controls matched for age, sex, and social class. Although 18 of the children who had had bronchiolitis in infancy had experienced subsequent episodes of wheezing, these were neither severe nor frequent in most cases and had apparently ceased by the age of 8. Nevertheless, the mean exercise bronchial lability of the children who had had bronchiolitis was significantly higher than that of the control children and the mean peak expiratory flow rate at rest significantly lower.

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. Diagnosis and clinical significance of parainfluenza virus infections in children. The diagnosis and clinical features of parainfluenza virus infections are described in 151 children admitted to hospital over a 2-year period. Immunofluorescence was the most sensitive method of laboratory diagnosis, while virus isolation in tissue culture was more often achieved from nasopharyngeal secretions than from cough/nasal swabs. Parainfluenza viruses were responsible for approximately 9% of 1603 acute respiratory admissions. Croup was the commonest of the wide range of respiratory illnesses associated with these infections; in a series of 132 children with croup, a parainfluenza virus was identified in 42 %. 24 of the 151 children presented with febrile convulsions, and in a series of 209 children admitted with febrile convulsions, parainfluenza viruses were responsible for 11 %. 3 of the children died in hospital with their parainfluenza virus infections, and in addition there was one instance of a close association between parainfluenza virus type 3 infection and the sudden unexpected death of an infant at home. Parainfluenza virus types 4a and 4b, which have so far rarely been identified, were isolated from 16 children.The age distribution and seasonal patterns of the infections are described. Attention is drawn to the risks of cross-infection by parainfluenza viruses in children's wards, and the finding that virus is commonly excreted for at least a week after the onset of the illness.

Nasopharyngeal secretions from adults and children were obtained in Stockholm, Sweden, for routine diagnosis of influenza A virus, influenza B virus, respiratory syncytial (RS) virus, parainfluenza type 3 virus, and adenovirus infections by demonstration of viral antigens directly in the specimens. The cells in nasopharyngeal secretions were pelleted by centrifugation for preparation of cell deposits for diagnosis by the immunofluorescence technique (IF) in London, England, and in Stockholm, whereas the supernatants were used to diagnose infection by the enzyme-linked immunosorbent assay (ELISA) in Stockholm. Titrations of the various purified viruses showed that ELISA could detect viral antigens in amounts corresponding to 1 to 10 ng of virus protein per test well. In a series of 73 specimens tested for influenza A, RS, and parainfluenza type 3 viruses by IF in London and by ELISA in Stockholm, 15 of 18 RS, 14 of 15 influenza A, and 2 of 2 parainfluenza type 3 viral infections were diagnosed by ELISA as compared with IF, giving sensitivities for RS and influenza A viral diagnosis of 83 and 93%, respectively, and a specificity of 100%. In another series of specimens from 35 patients tested for influenza B virus and adenovirus, five influenza B virus and four adenovirus infections were diagnosed by both methods; one additional influenza B infection was detected only by IF and another only by ELISA. Comparisons of diagnostic results between the two methods performed in Stockholm gave nonagreement of results for 37 of 1,593 tests (2.5%) for the five viruses. The conclusion reached was that the described ELISA, although a satisfactory test, had somewhat less sensitivity than did IF for the detection of respiratory viral infections. This could possibly be explained by unnecessary dilutions of specimens at the time of collection; transportation, processing, and storage of specimens were less complicated than for IF.

SummaryDuring a period covering four winter epidemics 987 respiratory syncytial (RS) virus infections were identified in the children's wards that served a total population of about 875 000 in north-east England. The incidence of admission to hospital with RS virus infection tended to be twice as high among children in Tyneside as that among children from the rest of the catchment area. The risk of hospital admission with RS virus infection in the first year of life for city children was about 1 in 50. The risk tended to be increased when there was a high proportion of children in the population, overcrowded housing, and unemployment. There was no clear relation between climatic changes and the onset or progress of epidemics. Thirteen deaths associated with RS virus infection were identified, four of them sudden and unexpected at home, and nine of them in children with congenital or acquired abnormalities. Twelve children were admitted twice with distinct RS virus infections; the relative severity of their two illnesses depended on age. Hospital cross-infection accounted for 60 of the 987 illnesses.Large families and overcrowding among poorer families seem to lead to a higher incidence of RS virus infection, and measures to reduce overcrowding and improve housing should help to reduce the spread of infection. Breast-feeding also protects infants from infection, but further information is needed to pinpoint the infants at greater risk and how they may best be protected.