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N J Gay

Publications and source records attributed to N J Gay.

At least 37 records · Page 2Linked to original sources
PubMed2002

The difficult quest for data on "vanishing" vaccine-preventable infections in Europe: the case of measles in Flanders (Belgium).

We aimed to describe the impact of vaccination on the epidemiology of measles infection in Flanders (Belgium), to document probable vaccination coverage based on this evidence, compare these epidemiological data with those generated by a mathematical model and estimate the costs of morbidity from measles. In contrast to previous analyses, we included the costs of long-term care for sequelae due to encephalitis and subacute sclerosing panencephalitis (SSPE). We estimated the direct health care costs per average measles case at 227, 212, 210, 200 and 194 for the age groups of 0-4, 5-9, 10-14, 15-19 and > or=20 years, respectively. Excluding long-term care lowers these estimates by 22-51%, depending on the age group. By including indirect time costs, we arrive at total costs per measles case of 320, 305, 210, 200 and 625, respectively. In addition to registering vaccination coverage more rigorously in the future, it seems necessary to undertake seroprevalence studies to document the age-specific immunity to measles. By using such information, current vaccination strategies can be adapted to prevent future outbreaks and to help eliminate measles from Europe in an efficient way. We noted throughout that many of the data sources are flawed. Better and accessible data bases are required to improve the reliability of similar studies in the future.

Adolescent↗
PubMed2002

Exposure to varicella boosts immunity to herpes-zoster: implications for mass vaccination against chickenpox.

We present data to confirm that exposure to varicella boosts immunity to herpes-zoster. We show that exposure to varicella is greater in adults living with children and that this exposure is highly protective against zoster (Incidence ratio=0.75, 95% CI, 0.63-0.89). The data is used to parameterise a mathematical model of varicella zoster virus (VZV) transmission that captures differences in exposure to varicella in adults living with and without children. Under the 'best-fit' model, exposure to varicella is estimated to boost cell-mediated immunity for an average of 20 years (95% CI, 7-41years). Mass varicella vaccination is expected to cause a major epidemic of herpes-zoster, affecting more than 50% of those aged 10-44 years at the introduction of vaccination.

Adolescent↗
PubMed2002

Immunogenicity of second dose measles-mumps-rubella (MMR) vaccine and implications for serosurveillance.

Measles and mumps, but not rubella, outbreaks have been reported amongst populations highly vaccinated with a single dose of measles-mumps-rubella (MMR) vaccine. Repeated experience has shown that a two-dose regime of measles vaccine is required to eliminate measles. This paper reports the effect of the first and second MMR doses on specific antibody levels in a variety of populations.2-4 years after receiving a first dose of MMR vaccine at age 12-18 months, it was found that a large proportion of pre-school children had measles (19.5%) and mumps (23.4%) IgG antibody below the putative level of protection. Only a small proportion (4.6%) had rubella antibody below the putative protective level. A total of 41% had negative or equivocal levels to one or more antigens. The proportion measles antibody negative (but not rubella or mumps) was significantly higher in children vaccinated at 12 months of age than at 13-17 months. There was no evidence for correlation of seropositivity to each antigen, other than that produced by a small excess of children (1%) negative to all three antigens. After a second dose of MMR, the proportion negative to one or more antigens dropped to <4%. Examination of national serosurveillance data, found that following an MR vaccine campaign in cohorts that previously received MMR, both measles and rubella antibody levels were initially boosted but declined to pre-vaccination levels within 3 years. Our study supports the policy of administering a second dose of MMR vaccine to all children. However, continued monitoring of long-term population protection will be required and this study suggests that in highly vaccinated populations, total measles (and rubella) IgG antibody levels may not be an accurate reflection of protection. Further studies including qualitative measures, such as avidity, in different populations are merited and may contribute to the understanding of MMR population protection.

Antibodies, Viral↗
PubMed2002

A mathematical model to measure the impact of the Measles Control Campaign on the potential for measles transmission in Australia.

BACKGROUND: The aims of this study were to determine the impact of the Australian Measles Control Campaign (MCC) on the transmission dynamics of measles by calculating the reproductive number (R) before and after the MCC, and to predict measles control in Australia in the future. METHODS: A national serosurvey was conducted before and after the MCC. Sera were tested for anti-measles IgG using enzyme immunoassay (EIA). A mathematical model, using serosurvey results and vaccine coverage estimates, was used to calculate the change in R after the MCC. RESULTS: The values of R calculated before and after the MCC were 0.90 and 0.57. At vaccine coverage levels indicated by the Australian Childhood Immunisation Register (ACIR), the value of R will exceed 1 (the epidemic threshold) in 2007-2008 nationally, and sooner in some regions of Australia. Coverage of at least 84% with two doses of MMR is required to sustain measles control. CONCLUSIONS: The Australian MCC had a significant impact on the transmission dynamics of measles. However, current vaccine coverage levels may result in indigenous measles transmission by 2007. Sustained efforts are required to improve coverage with two doses of MMR and to ensure elimination of indigenous measles transmission.

Adolescent↗
PubMed2002

The burden of Helicobacter pylori infection in England and Wales.

The prevalence of active infection with Helicobacter pylori in the general population of England and Wales was estimated using high reactivity for specific IgG in serum ELISA as a marker. A total of 10,118 anonymized residues of serum samples collected in 1986 and 1996 from persons aged 1-84 years were used. Estimated prevalence of active infection varied by region and was highest in London. Prevalence was related to decade of birth and increased from 4-3% in those born during the 1980s to 30% in those born before 1940. An estimated total of 7.5 million people living in England and Wales have an active infection and analysis by decade of birth showed no significant difference between samples collected in 1986 and 1996. These data suggest H. pylori infection is becoming less common, is acquired at an early age and is unlikely to be resolved unless suitable antimicrobial treatment is sought.

Adolescent↗
PubMed2002

The changing epidemiological pattern of hepatitis A in England and Wales.

Sera from an age-stratified sample of 4188 individuals, submitted for diagnostic purposes to 15 public health laboratories in England and Wales in 1996, were tested for hepatitis A antibody. The serological profiles were consistent with declining incidence in the past. This hypothesis was tested by comparing the serological profiles of Ashford, Leeds and Preston public health laboratories with those from sera collected during a previous study in the same laboratories in 1986/7. A comparison of equivalent 10 year birth cohorts revealed that significant hepatitis A seroconversion had only continued in Ashford. However, it is probable that most seroconversions are due to vaccination and immigration rather than continuing viral transmission. Further population-based surveys collecting more in-depth social and demographic data are needed to confirm the main factors influencing hepatitis A seroprevalence and to explain the regional differences.

Adolescent↗
PubMed2002

Contribution of RSV to bronchiolitis and pneumonia-associated hospitalizations in English children, April 1995-March 1998.

Estimates of the number of hospitalizations attributable to specific pathogens are required to predict the potential impact of vaccination. All hospital admissions for lower respiratory tract infection (LRI) in children < 5 years in England in 1995-8 were reviewed. Most admissions (76.8%) were not associated with specific organisms. Seasonality in pathogens that cause bronchiolitis and pneumonia was used to predict the proportion of cases with unspecified aetiology attributable to different organisms using multiple linear regression. Of 12,298 admissions for LRI, 17.5% were due to RSV infection. An estimated 74.8% (95% CI, 72.0-77.7%) of 'unspecified bronchiolitis' admissions and 16.3% (95% CI, 13.7-18.8%) of unspecified pneumonia' admissions were RSV related. The total mean annual incidence of hospital admissions attributable to RSV is 28.3/1000 children < 1 year of age, and 1.3/1000 children 1-4 years old. The greater burden of RSV infection than indicated through discharge data is revealed through applying simple statistical methods.

Bronchiolitis↗
PubMed2002

The prevalence of hepatitis C in England and Wales.

OBJECTIVES: To estimate the background population prevalence of hepatitis C in England and Wales, observe the prevalence over time and assess the extent of infection outside of known risk groups. METHODS: Sera from residual specimens from adult patients submitted to laboratories in England and Wales were tested for anti-HCV. Testing was carried out using a cost-effective pooling strategy. RESULTS: Although the prevalence of anti-HCV was highest in 1986 (1.07%), in the multivariable analysis, prevalence did not vary significantly between the 3 periods 1986, 1991 and 1996 (P=0.14). The prevalence of infection was higher in males than in females (P=0.0013). An age-period-cohort analysis revealed a cohort effect due to a lower HCV prevalence in the most recent birth cohorts, that is, those born between the calendar years 1971-1975 and 1976-1980. CONCLUSIONS: The majority of HCV infections in England and Wales were probably acquired before 1986. Infections in younger males identified in 1996 may signify more recent acquisition by injecting drug use.

Adult↗
PubMed2001

Amphiphysin is necessary for organization of the excitation-contraction coupling machinery of muscles, but not for synaptic vesicle endocytosis in Drosophila.

Amphiphysins 1 and 2 are enriched in the mammalian brain and are proposed to recruit dynamin to sites of endocytosis. Shorter amphiphysin 2 splice variants are also found ubiquitously, with an enrichment in skeletal muscle. At the Drosophila larval neuromuscular junction, amphiphysin is localized postsynaptically and amphiphysin mutants have no major defects in neurotransmission; they are also viable, but flightless. Like mammalian amphiphysin 2 in muscles, Drosophila amphiphysin does not bind clathrin, but can tubulate lipids and is localized on T-tubules. Amphiphysin mutants have a novel phenotype, a severely disorganized T-tubule/sarcoplasmic reticulum system. We therefore propose that muscle amphiphysin is not involved in clathrin-mediated endocytosis, but in the structural organization of the membrane-bound compartments of the excitation-contraction coupling machinery of muscles.

Animals↗
PubMed2001

Measles vaccination in Africa: by how much could routine coverage be improved?

Assuming that the level of Bacille Calmette Guerin (BCG) coverage gives a measure of access to immunisation services, it is possible to derive what fraction of infants are not immunised against measles due to under-utilisation of existing services (rather than unavailability of services). According to the most recent official statistics, the overall coverage for measles vaccine is 53% in Africa (10% lower than for BCG). This difference amounts to 3 million African children who will not be vaccinated against measles this year even though they probably have access to immunisation services.

Africa↗
PubMed2001

A family of proteins related to Spätzle, the toll receptor ligand, are encoded in the Drosophila genome.

The Drosophila gene Spätzle encodes the activating ligand for the Toll receptor. This signaling pathway is required for dorso-ventral patterning in the early embryo and an antifungal immune response in larvae and adults. The genome sequence of Drosophila shows that there are a total of eight Toll-like receptors and these may function in other aspects of embryonic development and innate immunity. Here we describe five Drosophila homologues of Spätzle (Spz2-6) found using an iterative searching method. All five appear to encode proteins containing neurotrophin-like cystine-knot domains. In addition, most retain a characteristic intron-exon structure shared with the prototype Spätzle gene. This provides evidence that the family arose by ancient gene duplication events and indicates that the gene products may represent activating ligands for corresponding Toll receptors. Expression studies show that only Spz4 is expressed strongly in larvae and adults and thus may be involved in an ancillary antifungal response mediated by Toll-5. By contrast, Spz6 shows a complex spatial and temporally regulated expression pattern in the late embryo. Thus the new Toll/Spätzle families of signaling molecules may have important roles in other aspects of development and immunity.

Amino Acid Sequence↗
PubMed2001

Drosophila embryos lacking N-myristoyltransferase have multiple developmental defects.

Lipid modification of proteins by the addition of myristic acid to the N-terminal is important in a number of critical cellular processes, for example, signal transduction and the modulation of membrane association by myristoyl switches. Myristic acid is added to proteins by the enzyme N-myristoyltransferase (NMT) and in this paper we detail the effects on embryonic development of a null mutation in the Drosophila NMT gene. Mutant embryos display a range of phenotypes, including failures of head involution, dorsal closure, and germ-band retraction, morphogenetic processes that require cellular movements. Embryos with milder phenotypes have more specific defects in the central nervous system, including thinning of the ventral nerve chord and, in some embryos, specific scission at parasegment 10. Staining of mutant embryos with phalloidin shows that the mutant embryos have a disrupted actin cytoskeleton and abnormal cell morphology. These phenotypes are strikingly similar to those caused by genes involved in dynamic rearrangement of the actin cytoskeleton. For example the myristoylated nonreceptor tyrosine kinases Dsrc42A and Dsrc64B were shown recently to be key regulators of dorsal closure. In addition, analysis of cell death reveals widespread ectopic apoptosis. Our findings are consistent with the hypothesis that the myristoyl switches and signaling pathways characterized at the biochemical level have important functions in fundamental morphogenetic processes.

Abnormalities, Multiple↗
PubMed2001

Epidemiology of varicella zoster virus infection in Canada and the United Kingdom.

Many countries are currently studying the possibility of mass vaccination against varicella. The objective of this study was to provide a comprehensive picture of the pre-vaccine epidemiology of the varicella zoster virus (VZV) to aid in the design of immunization programs and to adequately measure the impact of vaccination. Population-based data including physician visit claims, sentinel surveillance and hospitalization data from Canada and the United Kingdom were analysed. The key epidemiological characteristics of varicella and zoster (age specific consultation rates, seasonality, force of infection, hospitalization rates and inpatient days) were compared. Results show that the overall epidemiology of varicella and zoster is remarkably similar between the two countries. The major difference being that, contrary to Canada, the epidemiology of varicella seems to be changing in the United Kingdom with an important decrease in the average age at infection that coincides with a significant increase in children attending preschool. Furthermore, differences exist in the seasonality between the United Kingdom and Canada, which seem to be primarily due to the school calendar. These results illustrate that school and preschool contact patterns play an important role in the dynamics of varicella. Finally, our results provide baseline estimates of varicella and zoster incidence and morbidity for VZV vaccine effectiveness and cost-effectiveness studies.

Adolescent↗
PubMed2001

Estimation of measles reproduction ratios and prospects for elimination of measles by vaccination in some Western European countries.

The objective of this study is to estimate the measles reproduction ratio for eight Western European vaccination programmes. Because many plausible age-structured transmission patterns result in a similar description of the observations, it is not possible to estimate a unique value of the reproduction ratio. A method is developed to estimate bounds and confidence intervals for plausible values of the reproduction ratios using maximum likelihood methods. Lower and upper bounds for plausible values of the basic reproduction ratio are estimated to be 7.17 (95% CI 7.14-7.20) and 45.41 (95% CI 9.77-49.57), corresponding to lower and upper bounds on critical vaccine coverage of 86.6% and 98.1%. Of the eight evaluated vaccination programmes, four have vaccine coverage below the lower bound and allow measles to persist, and four have vaccine coverage at the upper bound and may eventually eliminate measles.

Adolescent↗
PubMed2000

Analysis of varicella vaccine breakthrough rates: implications for the effectiveness of immunisation programmes.

The objective of this study was to quantify key parameters describing varicella zoster virus (VZV) vaccine efficacy. To do so a mathematical model was developed to represent breakthrough cases as a function of time after vaccination in vaccine efficacy trials. Efficacy parameter sets were identified by fitting the predicted annual number of breakthrough infections with that observed in three clinical trials chosen to represent the plausible range of vaccine efficacy. Results suggest that varicella vaccination seems to result in a high proportion of individuals who are initially totally protected (97% for the base-case). However, individuals lose full protection relatively rapidly (3% per year for the base-case). Once total protection has waned individuals have a high probability of developing a breakthrough infection if exposed to varicella (73% of the probability in unvaccinated susceptibles for the base-case). Results also highlight that vaccine efficacy parameters should be estimated concurrently to take into account dependencies between parameters.

Child, Preschool↗