Biomedical subjects
Publications and source records attributed to D Isaacs.
Cytotoxic T-lymphocytes (CTL) recognize virus-infected cells in association with HLA class I antigens. There is strong evidence of the importance of CTL in respiratory syncytial virus (RSV) infections. We looked for but were unable to demonstrate an association between particular HLA class I antigens and severe RSV bronchiolitis in infants.
Production of interferon alfa in vitro was significantly reduced during acute respiratory syncytial virus bronchiolitis but subsequently returned to normal. Nasopharyngeal and endotracheal interferon alfa were detected intermittently and in low concentrations. The degree of impairment of in vitro production and poor in vivo production of interferon alfa suggest the need for a therapeutic trial of nebulised or systemic interferon in acute bronchiolitis.
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A prospective survey of children in the Oxford region identified 200 cases of systemic Haemophilus influenzae type b disease in the first three and a half years of the study. The annual incidence in children less than 5 years of age was 33.4/100,000. This represents a cumulative incidence of one systemic infection in 600 children before their 5th birthday. The mortality was 5.0%. The risk of H influenzae type b meningitis was one in 850 with a mortality of 5.6%, and substantial morbidity among survivors. From the total live birth rate, about 1300 cases of systemic H influenzae type b disease, over 900 cases of H influenzae type b meningitis, and 65 deaths would be predicted annually in children in the United Kingdom.
The safety and immunogenicity of a Haemophilus influenzae type b conjugate vaccine was investigated in 103 infants immunised at 3, 5, and 9 months of age; the infants also received diphtheria, pertussis, and tetanus and polio vaccines. Side effects were compared with 99 matched infants receiving diphtheria, pertussis, and tetanus and polio vaccines only. No serious side effects were observed and the incidence of minor side effects was no greater in the recipients of H influenzae type b conjugate vaccine. Two doses of the vaccine (standard and low) were compared: geometric mean titres of serum anticapsular antibody rose from 0.11 microgram/ml before immunisation to 26.4 micrograms/ml after three immunisations with the standard dose and 14.6 micrograms/ml with the low dose. The geometric mean titre among 21 unimmunized infants at this age was 0.06 micrograms/ml. Both doses therefore generated antibody concentrations likely to be protective after three immunisations. There were no non-responders. Incorporation of an H influenzae type b conjugate vaccine into the primary immunisation schedule has the potential for preventing over 1000 cases of systemic H influenzae type b disease and 50 deaths each year in the United Kingdom.
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Fifty-seven children ages 1 month to 12 years hospitalized because of community-acquired pneumonia were compared with age-matched controls who had acute asthma without pneumonia to test the value of rapid bacterial antigen detection and clinical and radiographic criteria for diagnosis of bacterial pneumonia. Bacterial pneumonia, defined on the basis of positive cultures of blood or pleural fluid, was diagnosed in 4 children (7%), 1 of whom also had viral pneumonia. Viral pneumonia, defined as a positive nasopharyngeal sample or positive serology, was diagnosed in 20 children (35%). Serum and concentrated urine were tested by latex agglutination (Wellcogen) for Haemophilus influenzae type b and pneumococcal antigens and by countercurrent immunoelectrophoresis for pneumococcal antigens. Pneumococcal antigen could not be detected in serum or urine from 3 children with culture-proved pneumococcal pneumonia, indicating poor sensitivity of the tests. In contrast apparent H. influenzae type b antigenuria was detected by latex agglutination in 4 of 40 children with pneumonia but also in 5 of 57 controls, and a sensitive enzyme-linked immunosorbent assay for polyribosyl ribitol (PRP) phosphate antigen showed that all 9 cases were false positives. The specificity of H. influenzae type b antigen detection was thus poor. Children with viral and bacterial pneumonia could not be distinguished by radiographic or clinical criteria (symptoms, fever) or by total or differential white blood cell counts, serum C-reactive protein or nasal or serum interferon levels. It is not possible to distinguish reliably childhood viral from bacterial pneumonia clinically or by rapid diagnostic tests.
During a 27 month study seven nonserotypable strains of Haemophilus influenzae and two of Haemophilus parainfluenzae were isolated from nine neonates. Seven had early infection associated with respiratory distress or conjunctivitis; three had septicaemia one of whom died. The incidence of haemophilus septicaemia was 0.23 per 1000 live births.
The proportion of babies colonised with gentamicin resistant Gram negative organisms in a nursery over a 30 month period did not correlate with the quantity or duration of aminoglycosides used, but it did correlate with two indicators of workload: the number of baby days and a score based on the level of nursing care required. Spread of resistant organisms may be more likely as workload increases.
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A cell-mediated cytotoxic response to respiratory syncytial (RSV) was demonstrated in the peripheral blood of 4 of 22 infants with acute bronchiolitis. These 4 infants were aged 3 weeks to 3 months. No such response was found in infants older than 4 months. All 4 infants with a positive response had mild infections.
Twenty-seven newborns had an episode of late-onset sepsis (septicaemia or bacterial meningitis after 48 h of age) over an 18 month period. Preceding or simultaneous surface cultures were available from 26 babies. Colonization with the organism causing sepsis could only be documented in 10 cases. Colonization with aminoglycoside-resistant Gram negative organisms was common but there were only two cases of systemic sepsis with a resistant organism. Pseudomonas aeruginosa frequently colonized babies over the first 8 months of the survey, but subsequently virtually ceased to colonize babies, although it continued to be a common cause of late-onset sepsis. These findings do not support the utility of routine surveillance of organisms colonizing neonates in predicting bacteria causing late-onset sepsis. They also cast doubt on the value of eliminating colonizing organisms by expensive infection control measures.
This paper describes two surveys carried out at the accident and emergency department of Queen Elizabeth Hospital, a specialist children's hospital situated in the east end of London. Both studies explored factors influencing attendance at the accident and emergency department. One was based on an analysis of recorded information (hospital notes) for a random sample of attenders, spread over a 12-month period. The second was based on personal interviews with a sample of children's parents. Both studies found problems with access to general practitioner care to be the main factors influencing attendance.
The serum acute phase reactants, C-reactive protein (CRP) and orosomucoid, rose significantly within 24 to 48 hours of presentation in infants with definite necrotizing enterocolitis (NEC) compared with the levels in infants with symptoms who tolerated early reintroduction of enteral feeds. A serum CRP value greater than 10 mg/l within 48 hours identified infants with definite NEC with a 92% sensitivity and an 81% specificity. Serum CRP values remained elevated at 7 to 10 days in 4 infants with late septicaemia and in 4 of 5 infants with abscess or early stricture requiring surgery. Serum acute phase reactants are a potentially valuable adjunct to clinical assessment in the management of infants with suspected NEC.
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A survey of the use of antibiotics in a neonatal unit for two years showed a considerable reduction in the mean duration of courses prescribed without any appreciable change in morbidity.