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Biomedical subjects

N Begg

Publications and source records attributed to N Begg.

At least 19 recordsLinked to original sources
PubMed1999

Immunogenicity and reactogenicity in UK infants of a novel meningococcal vesicle vaccine containing multiple class 1 (PorA) outer membrane proteins.

The development of effective vaccines against serogroup B meningococci is of great public health importance. We assessed a novel genetically engineered vaccine containing six meningococcal class 1 (PorA) outer membrane proteins representing 80% of prevalent strains in the UK. 103 infants were given the meningococcal vaccine at ages 2, 3 and 4 months with routine infant immunisations, with a fourth dose at 12-18 months. The vaccine was well tolerated. Three doses evoked good immune responses to two of six meningococcal strains expressing PorA proteins contained in the vaccine. Following a fourth dose, larger bactericidal responses to all six strains were observed, suggesting that the initial course had primed memory lymphocytes and revaccination stimulated a booster response. This hexavalent PorA meningococcal vaccine was safe and evoked encouraging immune responses in infants. Vaccines of this type warrant further development and evaluation.

Antibodies, Bacterial↗
PubMed1999

Meningococcal serogroup C conjugate vaccine is immunogenic in infancy and primes for memory.

The safety, immunogenicity, and immunologic priming of 2 dosages (2 microgram or 10 microgram) of a meningococcal C oligosaccharide-CRM197 conjugate vaccine was evaluated in 114 infants vaccinated at ages 2, 3, and 4 months. Antibody persistence and response to boosting with 10 microgram of meningococcal C polysaccharide were assessed. The meningococcal conjugate vaccine produced fewer local reactions than concurrent routine immunizations. Total serogroup C-specific immunoglobulin geometric mean concentration (GMC) increased from 0.3 microgram/mL before vaccination to 13.1 microgram/mL at age 5 months. Serum bactericidal antibody (SBA) geometric mean titers (GMTs) rose from <1:4 to 1:1057 at 5 months and fell by 14 months to 1:19. Following boosting, anti-C-specific immunoglobulin GMC rose to 15.9 microgram/mL and SBA GMT to 1:495. Antibody responses in the 10-microgram dose cohort were significantly higher at 5 months (P<.01) than in the 2-microgram dose cohort but were lower after polysaccharide boosting (P=.02). This meningococcal conjugate vaccine was well tolerated and immunogenic and induced immunologic memory in infants.

Bacterial Capsules↗
PubMed1999

Neutralising antibody responses to two doses of measles vaccine at 5 and 13 months of age in the United Kingdom.

Fifty-three children born in the United Kingdom between April 1993 and July 1994 were given two doses of measles vaccine, at 5 and 13 months of age, and their neutralising antibody reports were studied to assess the feasibility of protecting infants (aged 1 to 11 months) in the event of an outbreak or who were due to travel abroad. Sixteen infants responded at 5 months, an additional 35 responded at 13 months and two did not respond. The responses were inversely related to the levels of maternal antibodies (p < 0.0001). Infants who responded at 5 months also produced higher responses at 13 months than those who did not respond initially (p = 0.0001). No serious side effects were encountered. These data suggest that measles vaccine protects 30% of infants at 5 months and that a second dose at 13 months results in almost universal seroconversion.

Analysis of Variance↗
PubMed1997

A retrospective survey of clusters of meningococcal disease in England and Wales, 1993 to 1995: estimated risks of further cases in household and educational settings.

Information about the epidemiology of meningococcal disease case clusters and the risk of further cases is sparse. Data on clusters in household and educational settings from 1 January 1993 to 31 March 1995 was requested from consultants in communicable disease control in England and Wales through a retrospective postal survey. Ninety-three per cent (122/131) responded. Of the 114 cases in 45 reported clusters, 77 (67.5%) were microbiologically confirmed. The case fatality rate in index cases was higher than in associated cases (18.2% vs 4.5%; p = 0.02). Five out of 11 clusters in household settings consisted only of index and co-primary cases. No further cases occurred within two weeks after giving chemoprophylaxis to household contacts. The relative risks of further cases in the week after the index case arose were estimated to be 1200 for contacts in the household, 160 in secondary schools, 60 in primary schools, 1.8 in universities/colleges, and 0 in nurseries. Between seven and 30 days the relative risks were lower; 150 in households, and between 0 and 13 in all other settings. Beyond 30 days, the relative risk in the household setting was 8 and lower than this in all other settings. The absolute risk of further cases in the month following the index case was calculated as 210 per 100,000 in household members, 7-10/10(5) in pupils at the same school, and 0.6/10(5) in students at the same university or college. The current policy in England and Wales to recommend chemoprophylaxis for household members may prevent half of the further cases in this setting. Raised awareness may have contributed to the lower case fatality rate among household contacts who developed meningococcal disease, but the number of co-primary cases observed should prompt urgent enquiries about current illness in household contacts of index cases. The relative risk of further cases in preschool groups was low and apparently unaffected by changes in chemoprophylactic policy. The relative risk in school settings was raised in the month following a case, but the absolute risk was still low. Further study to quantify the risk in university settings is needed.

Adolescent↗
PubMed1997

Lone parent families are an independent risk factor for lower rates of childhood immunisation in London.

The aim of this study was to determine associations between indicators of social deprivation and the uptake of primary immunisation in London. Correlation coefficients were calculated between immunisation coverage in London for each of the 28 inner and outer London district health authorities in November 1991 and a range of possible explanatory variables from small area statistics data from the November 1991 census. The proportions of children under 5 years of age, lone parent families, unemployed members of the workforce, domestic overcrowding, ethnic minorities, and unskilled workforce were correlated significantly with the coverage of primary immunisation for third dose diphtheria (D3) and pertussis (P3) at 12 months. A significant correlation with measles, mumps, and rubella (MMR) at 24 months existed only for lone parent families. Multiple linear regression weighted by population size was used to identify independent predictors of variation in immunisation cover. The proportion of lone parent families in each district health authority was the only significant independent risk factor consistently associated with variation in immunisation coverage for D3, P3, and MMR. The proportion of lone parent families explained 42% of the variation in coverage for D3 in November 1991. This study has identified lone parenthood as an important independent risk factor in London for failure to complete immunisation.

Adult↗
PubMed1997

Vaccine failures after primary immunisation with Haemophilus influenzae type-b conjugate vaccine without booster.

BACKGROUND: Diseases of early childhood associated with Haemophilus influenzae type b (Hib) can now be prevented by vaccination. The rapid implementation of routine infant vaccination with Hib polysaccharide-tetanus protein conjugate (PRP-T) vaccine has allowed us to assess whether an accelerated 2, 3, and 4 month schedule can protect in the longer term without a booster dose and whether carrier priming influences protective efficacy. The degree of protection afforded by a catch-up programme with Hib oligosaccharide conjugate (HbOC) for older children was also assessed. METHODS: Paediatricians and microbiologists in the UK were asked to report all cases of invasive H influenzae infection in children who had received at least one dose of Hib-conjugate vaccine. Serum samples from convalescent children were obtained and the isolate was verified. Efficacy was estimated by comparing observed rates of Hib disease in those who had been vaccinated with rates predicted by age adjustment of disease rates from the prevaccine era. FINDINGS: Of 164 reports of invasive infection between Oct 1, 1992, and Oct 1, 1995, 43 were considered true vaccine failures. The estimated overall efficacy for three doses of PRP-T was 98.1% (95% CI 97.3-98.7%). Efficacy in infants aged 5-11 months was 99.1%, 12-23 months 97.3%, and 24-35 months 94.7%. In infants aged 3-11 months, who received their first dose of PRP-T after tetanus toxoid vaccination, disease was unlikely from 1 week after one dose of PRP-T vaccine (88.6% protection in the second to fourth weeks [66.8-97.7%]). The disease rate in vaccinated infants aged 2 months has declined year on year. In children aged 13 months to 2 years given HbOC, as a catch-up vaccine, the estimated efficacy was 94.0% (84.7-98.4%). INTERPRETATION: A high degree of efficacy has been observed with PRP-T vaccine given as a three-dose schedule in infancy and with HbOC as a single dose in older children. Efficacy of PRP-T appears to be enhanced by carrier priming. Although with increasing age there was a small decline in efficacy of PRP-T, Hib disease is now close to being eliminated in the UK, and we suggest that a booster is not necessary in the second year of life.

Age Factors↗
PubMed1996

Conjugate meningococcal serogroup A and C vaccine: reactogenicity and immunogenicity in United Kingdom infants.

The reactogenicity and immunogenicity of a serogroup A and C meningococcal polysaccharide-CRM197 conjugate vaccine was evaluated in 58 infants who received three doses at 2, 3, and 4 months of age. The conjugate vaccine produced few systemic side effects, and local reactions were significantly less common than those produced by the routine vaccinations. The prevaccination geometric mean titers (GMTs) of A and C polysaccharide antibodies were, respectively, 2.8 and 0.6 microg/mL, rising to 21.5 and 38.5 microg/mL by 1 month after the third dose (age 5 months) and falling to 3.1 and 2.2 mircog/mL by 14 months of age. Prevaccination serum bactericidal titers against 2 serogroup C meningococci strains were <1/4 in 49 of 52 infants, rising to a GMT of 1/3082 at 1 month after the third dose and falling by age 14 months to a GMT of 1/10. Thus, this meningococcal conjugate vaccine proved to be safe and immunogenic, inducing high levels of anti-C polysaccharide antibodies that were bactericidal in young infants.

Antibodies, Bacterial↗
PubMed1995

A cluster of cases of streptococcal necrotizing fasciitis in Gloucestershire.

We describe the first cluster of cases of necrotizing fasciitis (NF) in this century in the United Kingdom (UK). Between 1 January and 30 June 1994 there were six cases (five confirmed, one probable) of Streptococcus pyogenes NF in west Gloucestershire, population 320,000. Two cases died. The first two patients probably acquired their infections during the course of elective surgery performed in the same operating theatre, possibly from a nasopharyngeal carrier amongst the theatre staff. The remaining infections were community-acquired. Of 5 S. pyogenes isolates there were 2 M1 strains, 1 M3, 1 M5 and 1 M non-typeable strain. S. pyogenes NF had not been recorded in west Gloucestershire in the preceding 10 years and the incidence of S. pyogenes bacteraemia in England and Wales had not risen in the past 5 years. The two presumably theatre-acquired infections raised several issues. The need for detailed bacteriological investigation of all cases of post-surgical NF was confirmed. Clusters of S. pyogenes infection following surgery should be managed by closure of the operating theatre until all staff have been screened for carriage. Closure of an operating theatre and screening of staff following a sporadic case is probably not justified because of the infrequency of surgical cross-infection with S. pyogenes. Regular, routine screening of theatre staff is neither practical nor necessary.

Aged↗
PubMed1995

Avidity of specific IgG antibodies elicited by immunisation against Haemophilus influenzae type b.

AIM: To investigate the avidity of specific IgG polyribosyl ribitol phosphate (PRP) antibodies induced by three Haemophilus influenzae type b (Hib) conjugate vaccines: PRP-meningococcal outer membrane protein complex (PRP-OMP), PRP-non-toxic mutant diphtheria toxin, CRM197 (HbOC) and PRP-tetanus toxoid (PRP-T). METHODS: One hundred and ten infants were immunised with one of the vaccines at two, three and four months of age. Blood samples were taken after each vaccination and serum stored at -20 degrees C. Serum samples collected after the third course (that is, at five months of age) were submitted to antibody avidity assessment, using a urea enzyme linked immunosorbent assay (ELISA). RESULTS: All three conjugate vaccines elicited IgG PRP antibodies of high median avidity. The resultant antibody populations were heterogeneous with regard to avidity, which in turn was independent of PRP antibody concentration. CONCLUSIONS: With the recent findings of a correlation between bactericidal killing and affinity, our data highlight the need for a protective level to be expressed qualitatively as well as quantitatively.

Antibodies, Bacterial↗