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N J Gay

Publications and source records attributed to N J Gay.

At least 55 records · Page 3Linked to original sources
PubMed2000

Epidemiology of transmissible diseases after elimination.

Elimination of an infectious disease is often understood to mean the total absence of cases in a population. This situation can occur only if the entire population is immune as a result of either natural disease or vaccination. However, this costly and unrealistic scenario is not necessary to ensure elimination, more appropriately defined as a situation in which sustained transmission cannot occur and secondary spread from importations of disease will end naturally, without intervention. The authors describe the size and duration of outbreaks caused by imported infections after indigenous transmission has been eliminated. They show that the status of the elimination process can be monitored by assessing the proportion of cases imported and the distribution of outbreak sizes. Measles in Canada, the United States, and the United Kingdom provides a good example of the relevance of these criteria. Surveillance of the size and duration of these outbreaks enables maintenance of elimination to be monitored.

Canada↗
PubMed2000

Characterisation of the gene for Drosophila amphiphysin.

A sequence similarity search of the Drosophila nucleotide database using vertebrate amphiphysin as a query identified a cDNA that encodes a Drosophila amphiphysin. The predicted protein has conserved sequence domains that should enable it to dimerise and bind to dynamin. Structural modelling suggests that the Src-homology-3 (SH3) domains of vertebrate and Drosophila amphiphysins are highly similar, supporting the putative ability of the latter to bind dynamin. However, the fly amphiphysin shows less conservation to sequences in the vertebrate amphiphysins that bind other endocytic components such as clathrin, AP-2 and endophilin. Amphiphysin is a single-copy gene that maps to position 49B on polytene chromosomes. Messenger RNA of this amphiphysin is expressed widely during embryogenesis and has elevated expression in a number of sites including the foregut, hindgut and epidermis, but not in the central nervous system. Taken together, these data are consistent with a role for Drosophila amphiphysin in endocytosis, but the details of this role may differ from that of vertebrate amphiphysins.

Amino Acid Sequence↗
PubMed2000

Modelling rubella in Europe.

The prevention of congenital rubella syndrome (CRS), as a complication of rubella infection during pregnancy, is the main aim of rubella vaccination programmes. However, as vaccination of infants leads to an increase in the average age at which those who were not immunized become infected, certain rubella vaccination programmes can lead to an increase in the incidence of CRS. In this paper we use a mathematical model of the transmission dynamics of rubella virus to investigate the likely impact of different vaccination policies in Europe. The model was able to capture pre- and post-vaccination patterns of infection and prevalence of serological markers under a wide variety of scenarios, suggesting that the model structure and parameter estimates were appropriate. Analytical and numerical results suggest that endemic circulation of rubella is unlikely in Finland, the United Kingdom, The Netherlands, and perhaps Denmark, provided vaccine coverage is uniform across geographical and social groups. In Italy and Germany vaccine coverage in infancy has not been sufficient to interrupt rubella transmission, and continued epidemics of CRS seem probable. It seems unlikely that the immunization programmes in these countries are doing more harm than good, but this may be partly as a result of selective immunization of schoolgirls. Indeed, in both these countries, selective vaccination of schoolgirls with inadequate vaccination histories is likely to be an important mechanism by which CRS incidence is suppressed (unlike the other countries, which have had sufficiently high infant coverage rates to withdraw this option). Reducing inequalities in the uptake of rubella vaccine may bring greater health benefits than increasing the mean level of coverage.

Adolescent↗
PubMed2000

The pre-vaccination epidemiology of measles, mumps and rubella in Europe: implications for modelling studies.

Data on the pre-vaccination patterns of infection for measles, mumps and rubella are collated from a number of European countries in order to compare the epidemiology of the three viruses. Key epidemiological parameters, such as the age-specific force of infection and the basic reproduction number (R0) are estimated from case notification or serological data using standard techniques. A method is described to compare force of infection estimates derived from serological data. Analysis suggests that the pre-vaccination patterns of measles and mumps infection in the different countries were similar. In contrast, the epidemiology of rubella was highly variable between countries. This suggests that it may be acceptable to use parameter values estimated from other countries to model measles and mumps transmission, but that this approach to modelling rubella transmission requires more caution. Estimates of R0 depend on underlying mixing assumptions. Constraints were placed on R0 estimates by utilising knowledge of likely mixing patterns. The estimates for R0 were highest for measles, intermediate for mumps, and generally lowest for rubella. Analysis of within- and between-age-group transmission rates suggested that mumps transmission tends to be more concentrated within young children than the other two viruses. The implications for the design of immunization programmes are that mumps may be the easiest to control via infant immunization since it is predominantly transmitted between the very young and the variability in rubella epidemiology requires that careful consideration of the possible effects of vaccination options should be made using local data when planning rubella immunization programmes.

Adolescent↗
PubMed2000

Modelling the impact of immunization on the epidemiology of varicella zoster virus.

The objective of this study was to develop and apply a dynamic mathematical model of VZV transmission to predict the effect of different vaccination strategies on the age-specific incidence and outcome of infection. To do so a deterministic realistic age-structured model (RAS) was used which takes account of the increased potential for transmission within school aged groups. Various vaccine efficacy scenarios, vaccine coverages and vaccination strategies were investigated and a sensitivity analysis of varicella incidence predictions to important parameters was performed. The model predicts that the overall (natural and breakthrough) incidence and morbidity of varicella would likely be reduced by mass vaccination of 12-month-old children. Furthermore, adding a catch-up campaign in the first year for 1-11 year olds seems to be the most effective strategy to reduce both varicella incidence and morbidity (in the short and long term), though with the possible detrimental effect of increasing the incidence of zoster.

Adolescent↗
PubMed2000

The epidemiology of measles in Poland: prevalence of measles virus antibodies in the population.

WHO has adopted a goal of eliminating indigenous measles from the European Region by the year 2007. The strategy focuses on reducing the proportion of susceptible individuals in the population to low levels and maintaining these low levels of susceptibility. Routine vaccination against measles for children aged 13-15 months was introduced in Poland in 1975, and a second dose added in 1991. High coverage (> 95%) is achieved with both doses. In order to assess progress towards measles elimination in Poland, a serological survey was performed to evaluate the impact of vaccination on the susceptibility profile of population. Three thousand residual serum samples from individuals aged 1-30 years were collected from hospitals in six selected voivodeships (administration units) in Poland. These were tested for measles-specific IgG using a commercial ELISA. Overall 4% (120/3000) were negative for measles virus antibody. The highest proportion of negatives (8.2%) occurred among cohorts born 1977-81--the only cohorts in which susceptibility exceeded the WHO targets. 'Catch-up' vaccination strategies should target these cohorts.

Adolescent↗
PubMed2000

The burden of infection with HSV-1 and HSV-2 in England and Wales: implications for the changing epidemiology of genital herpes.

OBJECTIVE: To measure the burden of infection with herpes simplex type 1 (HSV-1) and herpes simplex type 2 (HSV-2) in the general population of England and Wales and to assess temporal changes in the incidence of HSV-1 infection in childhood. METHODS: 4930 residual blood samples taken from people aged 0-69 years and submitted to 15 public health laboratories in England and Wales between January 1994 and June 1995, and 500 samples taken from people aged 10-14 years between November 1986 and December 1987, were screened for IgG antibody to HSV-1 and HSV-2 using type specific ELISA assays. RESULTS: The prevalence of antibody to HSV-1 in 10-14 year olds declined from 34% in samples collected in 1986-7 to 24% in samples collected in 1994-5 (p < 0.001). HSV-1 antibody prevalence in adults increased with age and was higher in females than males, reaching 54% in females aged 25-30 years in 1994-5. In samples collected in 1994-5 from people aged 16-69 years HSV-2 antibody was detected in sera from 3.3% of men and 5.1% of women. CONCLUSIONS: The incidence of HSV-1 infection in childhood is falling in England and Wales. The prevalence of HSV-2 infection in the general population is low, with the rate of infection significantly lower than that described for the general population in the United States and developing countries. The falling rate of HSV-1 infection in childhood may be one factor contributing to the increasing incidence of genital HSV-1 infection.

Adolescent↗
PubMed1999

Formation and biochemical characterization of tube/pelle death domain complexes: critical regulators of postreceptor signaling by the Drosophila toll receptor.

In Drosophila, the Toll receptor signaling pathway is required for embryonic dorso-ventral patterning and at later developmental stages for innate immune responses. It is thought that dimerization of the receptor by binding of the ligand spätzle causes the formation of a postreceptor activation complex at the cytoplasmic surface of the membrane. Two components of this complex are the adaptor tube and protein kinase pelle. These proteins both have "death domains", protein interaction motifs found in a number of signaling pathways, particularly those involved in apoptotic cell death. It is thought that pelle is bound by tube during formation of the activation complexes, and that this interaction is mediated by the death domains. In this paper, we show using the yeast two-hybrid system that the wild-type tube and pelle death domains bind together. Mutant tube proteins which do not support signaling in the embryo are also unable to bind pelle in the 2-hybrid assay. We have purified proteins corresponding to the death domains of tube and pelle and show that these form corresponding heterodimeric complexes in vitro. Partial proteolysis reveals a smaller core consisting of the minimal death domain sequences. We have studied the tube/pelle interaction with the techniques of surface plasmon resonance, analytical ultracentrifugation and isothermal titration calorimetry. These measurements produce a value of K(d) for the complex of about 0.5 microM.

Amino Acid Sequence↗
PubMed1999

Interval-censored survival data with informative examination times: parametric models and approximate inference.

We develop parametric methods for analysing interval-censored data when examination and survival times are not independent. The hazard function is modelled by introducing individual frailties related to the frequency of examinations. Model parameters may be obtained by direct maximization of the marginal log-likelihood. We develop a simpler approximate method in which the frailties are estimated by empirical Bayes. The two approaches are equivalent asymptotically as the number of examinations on each individual increases. Simulations suggest that the approximate method is adequate for estimating regression parameters even when the number of examinations on each individual is small. The methods are used to estimate age and period effects on HIV incidence in a cohort of repeat attenders at genito-urinary clinics in London, U.K.

Adult↗
PubMed1999

The prevalence of hepatitis B infection in adults in England and Wales.

Cost effectiveness analyses of alternative hepatitis B vaccination programmes in England and Wales require a robust estimate of the lifetime risk of carriage. To this end, we report the prevalence of infection in 3781 anonymized individuals aged 15-44 years whose sera were submitted in 1996 to 16 microbiology laboratories in England and Wales. One hundred and forty-six individuals (3.9%) were confirmed as anti HBc positive, including 14 chronic carriers (0.37%). The prevalence of infection and carriage was higher in samples collected in London and increased with age. No increased risk of infection was seen in sera from genito-urinary (GUM) clinics. Only 15 sera positive for hepatitis B were also positive for hepatitis C. Our results confirm the low prevalence of hepatitis B in England and Wales, are consistent with previous estimates of carriage and suggest that many infections were acquired while resident outside the UK. Future prevalence studies should determine the country of birth and other risk factors for each individual in order to confirm these findings.

Adolescent↗
PubMed1999

Impact of rotavirus disease in Spain: an estimate of hospital admissions due to rotavirus.

The epidemiology of rotavirus infection in Spain was investigated using information from existing surveillance systems. Reports from laboratories and data on hospital admissions were used to estimate the number of hospital admissions due to rotavirus infection. Between January 1989 and December 1995 there were 8265 reports of rotavirus identification in the Sistema de Información Microbiológica, a voluntary national laboratory surveillance system. Where age was reported, 89.2% were in children under 5 y old. This represents 21.8% of all pathogens identified in faecal specimens in children of this age group. Between January and December 1994 there were 5639 admissions coded as "infectious intestinal disease" and 8225 as "non-infective gastroenteritis" in children under 5 y of age in the Conjunto Mínimo Básico de Datos, an obligatory hospital admissions surveillance system which covers 83% of public hospitals. Using regression analysis of admission data and laboratory reports it was estimated that rotavirus infection accounted for 3519 (25.3%) of the hospital admissions. We estimate that 4239 admissions attributable to rotavirus occurred in children under 5 y of age in Spain in 1994, a rate of 2.5/1000 population in this age group. These estimates are lower than those published for other countries, where the burden of disease is considered high enough to warrant a national vaccination programme. A cost-effectiveness study with Spanish information is essential before embarking on a national vaccination programme.

Child, Preschool↗
PubMed1998

Promoter sequence and expression of the leucine-rich repeat gene LRR47: evidence for cytoplasmic and nuclear localization in Drosophila embryos and cells.

In Drosophila, proteins containing leucine-rich repeats (LRR) play diverse roles during embryonic development. In particular, they function in cell adhesion and cellular signalling and have in common the ability to mediate reversible protein-protein interactions. The sequence and chromosomal location of Drosophila LRR47, which encodes a protein with eight LRR repeats, were reported previously. In this paper the 5' flanking region of the LRR47 gene is described and the initiation point for the maternal transcription unit is defined. LRR47 belongs to a subfamily of LRR proteins that have in common the ability to interact with ras GTPase. Whole-mount in situ hybridization studies show that the LRR47 transcript is uniformly distributed in early cleavage embryos but becomes depleted at the termini by the blastoderm stage. There is a specific requirement for ras function in the embryonic termini at this developmental stage. The distribution of LRR47 protein in embryos and tissue culture cells was also studied. The protein is present in both the cytoplasm and nuclei of embryos until gastrulation and is seen to persist in the nuclei of the amnioserosa until later stages of development. The protein is also constitutively present in growing SL2 culture cells and again is present in both cytoplasm and nuclei. These results suggest that LRR47 function may be modulated in the cell or nuclear division cycle.

Amino Acid Sequence↗
PubMed1998

Modelling the incidence of measles in Canada: an assessment of the options for vaccination policy.

A range of vaccination policy options for improving the control of measles in Canada is investigated using a mathematical model to simulate transmission of the disease. Results suggest that a catch up campaign giving a second dose of vaccine to children aged up to 18 years would have an immediate impact on transmission, which could be maintained by the introduction of a routine second dose at either 18 months or 5 years of age. Introducing a routine second dose of vaccine without a catch up campaign would allow continued endemic transmission of measles among older children for at least 10-15 years.

Adolescent↗