Biomedical subjects
Publications and source records attributed to E D McIntosh.
There is risk attached to the development of respiratory syncytial virus vaccines, live attenuated or otherwise, but without the acceptance of this risk by manufacturers, health providers and the public, the conclusion of successful Phase III trials may lie in the distant future.
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Natural variation in hepatitis B virus (HBV) was studied in asymptomatic carriers originating from countries of high endemicity. HBV DNA was detected by dot blot and/or polymerase chain reaction (PCR) in 34 of the 184 members of 22 new immigrant families who agreed to be tested after one of their children had been found to have current or past hepatitis B in a school survey. PCR products from both the S and distal-X pre-C regions were sequenced. One vaccinated child had the classical "escape" mutation at amino acid position 126 in the S-gene and two other children and two adults had other substitutions at amino acid positions 133, 120, 165, and 159. Mutations were more frequent in the distal-X pre-C region and included two pre-C mutants and 13 other amino acid substitutions. The strains originating in the various countries were placed in almost identical groups by phylogenetic analysis using each amplicon, and determination of subtype by antigenic analysis gave the same result as sequencing. The S-data allowed recognition of three dominant strains within genotype B, while the distal-X pre-C data provided better discrimination between family groups. No change was found when the sequence of samples obtained for the study was compared with those collected from 14 of the children two years earlier. There was some evidence of horizontal spread in addition to vertical transmission. Reports of mutations of HBV in patients with severe or unusual clinical features should be interpreted with caution until the prevalence of the mutant in asymptomatic carriers has been determined.
Using molecular finger-printing, we provided evidence that, in a children's day-care centre, a known hepatitis B virus (HBV) hepatitis B e antigen (HBeAg) carrier transmitted HBV to another child (the index case). The chronic HBV carrier had an exudative skin lesion and a history of biting. We sought to identify other at-risk children and prevent further transmission. Blood samples were collected and tested serologically for HBV. Of the 90 other children, 78 (87 per cent) were tested and none had serological evidence of HBV infection; 73 (81 per cent) were of Caucasian background; 38 (49 per cent) had a history of HBV immunisation with serological confirmation. Therefore, 1 (2.4 per cent, 95 per cent confidence interval 1.0 to 12.8 per cent) of the 41 known susceptible contacts became infected. The risk of horizontal HBV transmission in a children's day-care centre is low but not negligible. Staff and children should be vaccinated when a child in a day-care centre is a known HBV carrier.
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Fifty patients born with congenital rubella in 1939-1945 were reviewed in 1967. In 1991 this cohort was again studied and their ophthalmic features are presented here. The presence of two new cataracts and one case of possible choroidal neovascularisation are again noted; apart from these three eyes, the group showed no evidence of other delayed manifestations of the congenital rubella syndrome. A review is given of the ocular complications of the congenital rubella syndrome, with particular emphasis on the late complications.
The efficacy of antibiotic chemoprophylaxis in labour for all maternal carriers of Group B streptococcus with respect to the neonatal mortality and morbidity was analyzed. The intervention consisted of a policy of maternal screening for Group B streptococcus at 28 weeks' gestation by a low vaginal swab, cultured on to nonselective media. If positive, all carriers were treated with intrapartum ampicillin regardless of other obstetric risk factors. The main outcome measures were studied prospectively for 16 months before and for 32 months after instituting the intervention. These included the incidence of early-onset Group B streptococcal infection as defined by either a blood culture or a symptomatic neonate with a positive urinary streptococcal antigen test, the mortality and the morbidity. Intrapartum ampicillin significantly reduced the incidence of early-onset Group B streptococcal disease, from 2.0 to 0.37 per 1,000 livebirths for neonates with a positive blood culture (p < 0.03), and from 4.9 to 1.5 per 1,000 livebirths for symptomatic infants with a positive urinary antigen test (p < 0.004) and the attributable morbidity, namely, neonates who were: admitted to a level 2 or 3 unit (p < 0.004); treated with antibiotics (p < 0.004); preterm (p < 0.04); ventilated (p < 0.01). Seventy five per cent of the maternal population was overall actually screened and the carriage rate was 12%. No serious adverse reactions to ampicillin were observed. Significant reduction in early-onset neonatal Group B streptococcal disease has occurred concurrent with antepartum screening and nonselective intrapartum chemoprophylaxis.
Hepatitis B virus provides a model for studying the genetic variability and diversity of viruses. New molecular techniques such as the polymerase chain reaction and sequencing of amplified product enable the accurate pinpointing of genetic alteration. The immune response or lack of response to wild-type and mutant virus ultimately determines the extent of disease. Elimination of infection and disease may be achieved by natural, immunologic, and pharmacologic means, but definitive treatment may have to await the advent of gene therapy. Meanwhile, epidemiologic studies, vaccination programs, and cost-benefit analyses are important in the prevention and control of hepatitis B. Once the clinical and epidemiologic significance of mutant hepatitis B viruses is established, new strategies and vaccines will be required before elimination of the disease is achieved.
OBJECTIVE: To document the prevalence of hepatitis B virus (HBV) infection in urban Australian primary schoolchildren, and to look for evidence of horizontal transmission of HBV in schools between children at high risk of infection and those at low risk. We compared the prevalence of infection in a group of low-risk children attending control schools (less than 5% of students from high-risk groups) with the prevalence in low-risk children attending test schools (more than 20% of students from high-risk groups). METHODS AND RESULTS: Venous blood was collected and tested for hepatitis B markers by radioimmunoassay; 2883 children (1431 boys) of mean age 11.3 years (SD, 0.7) from 50 schools were tested. Evidence of past or current infection was present in 169 children (5.9%). This number comprised three of the 1347 low-risk children (0.2%), 10 of the 602 medium-risk children (1.7%), 154 of the 731 high-risk children (21.1%) and two of the 203 other children (1%). Fifty-four of the 169 infected children were hepatitis B surface antigen (HBsAg) positive, 36 of the 54 were also positive for hepatitis B e antigen (HBeAg). There was no difference between children in the low-risk group in test and control schools for markers of hepatitis B virus infection. CONCLUSIONS: A low prevalence of HBV infection was found in low-risk school-children irrespective of the proportion of high-risk children in their classes. Targeting vaccination to infants and children with known risk factors is the most important strategy in low endemicity countries; vaccination of children without risk factors could be delayed till early adolescence.
OBJECTIVE: To investigate an apparent increase in the number of children admitted to the Royal Alexandra Hospital for Children with extrapulmonary tuberculosis (TB). Further, to highlight both the seriousness of this disease and the difficulty of its diagnosis, and to draw attention to factors such as ethnic origin in identifying children at risk. DESIGN: Clinical and microbiological data were collected for all children admitted to the hospital with a confirmed diagnosis of TB. A standardised incidence ratio (SIR) was used to analyse the number of children admitted with extrapulmonary TB in 1990-1991 compared with 1982-1989, and in 1987-1991 compared with 1982-1986. RESULTS: Eleven children (five of these in 1990 and 1991) had extrapulmonary TB (4, central nervous system; 3, osteomyelitis; 2, cervical lymphadenitis; 2, abdominal). One was Aboriginal and 10 were from families of overseas origin. Twenty-one others had pulmonary TB and 17 of these were from families of overseas origin. The apparent increase in the number of admissions for extrapulmonary TB was not statistically significant. CONCLUSION: There has been a recent increase in the number of children hospitalised with extrapulmonary TB but when this is compared with the increase in children hospitalised for all causes, the increase is not significant. Immigration and the continuing contact of children with infected adults appear to account for most cases of TB in this series.
Respiratory syncytial virus (RSV) has two major antigenic groups, A and B. There is disagreement as to whether or not there is a difference in the clinical severity of disease caused by the two RSV groups. This 3-year prospective study of infants and children with RSV-positive bronchiolitis examines the relative virulence of RSV Groups A and B and assesses the role that breast-feeding may have in modifying the clinical severity of infection. Clinical severity was graded I (ventilated, severe), II (oxygen therapy, moderate), III (no ventilation or oxygen, mild). RSV serogrouping was performed. After exclusion of 60 subjects with known predisposing factors for severity, 444 infants and children were studied (Group A, 337; Group B, 107). The difference in proportion of subjects with severity grade I and II with Group A compared with Group B infection was 6% (95% confidence interval, 4.7 to 16.7). For infants 0 to 6 months of age this difference was 5.6% (95% CI, 7.3 to 18.4). Nineteen cases were nosocomially transmitted. There was a predominance of Group A RSV infection but no difference in severity between Group A and Group B infection.
50 patients with congenital rubella, born in 1939-43, were reviewed in 1967. Here we report their outcome in 1991. Since 1967, there have been 7 deaths (3 cardiovascular, 3 malignant disease, 1 AIDS). 40 had full clinical assessment. The prevalence of diabetes mellitus is similar to that in 1967: 4 of the 5 reported diabetic then, remain so, and there is 1 new case. 1 subject has malignant melanoma and 3 have died from cancer. Although the incidence of malignant disease is not increased, the death rate is (standardised mortality rate 6.0, 95% CI 1.24-17.57). Longer follow-up will be required to confirm this observation.
The aim of this study was to test the sensitivity and specificity of antigen detection for group B streptococcus (GBS) from the urine of neonates with early onset GBS sepsis. GBS sepsis was defined as early (< 48 hours) signs of sepsis in a neonate colonised with GBS. Neonates of 26 weeks' gestation or more, considered at risk for sepsis, were prospectively investigated for one year. Investigations included culture of superficial swabs to assess colonisation, blood culture, and the Wellcogen Strep B latex particle agglutination test on urine. Of 188 neonates investigated, 17 (9%) had GBS sepsis. The urine antigen test had a sensitivity of 88% and specificity of 98%. The positive predictive value was 79% and the negative predictive value 99%. Blood culture was positive in only five neonates (29%). The annual incidence of GBS sepsis was 4.0 per 1000 and of blood culture positive GBS disease was 1.2 per 1000 live births. Three neonates died. The application of the urine antigen test of clinical neonatal practice is discussed.