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E Miller

Publications and source records attributed to E Miller.

At least 37 records · Page 2Linked to original sources

A novel method of oral fluid collection to monitor immunity to common viral infections.

Serological surveys among representative population samples have proved rare given their reliance on invasive sample collection. We therefore completed the first population-based postal survey of immunity in England and Wales using new oral fluid technology. This paper examines the feasibility of this new methodological approach. Nearly 5500 oral fluid samples were collected, with individual demographic and social data via a questionnaire, from persons under 45 years of age recruited through general practices. Instructions were accurately followed with only 1% of samples returned without risk-factor data. The overall response rate was 40%. Response was independently associated with age, sex and location. Response was highest in children aged 5-14 years, adult females and in rural locations. This approach allowed the successful collection of comprehensive individual risk data, but response rates in adults must be improved if oral fluid surveys are to routinely complement serological surveillance.

Adolescent↗

Seroprevalence of antibody to varicella zoster virus in England and Wales in children and young adults.

This is the first large-scale study to investigate the seroprevalence of varicella zoster (VZV) in the general population of England and Wales. The study focused on those aged 1-20 years, that age group in whom most infections occur. Prevalence rose rapidly with age, with 53% of children showing evidence of prior infection by the age of 5 years and most young adults having experienced infection. In addition to using a fixed cut-off recommended by the manufacturer, a mixture modelling technique was also used to define the proportion of the population seropositive in each age group. This was shown to be a more accurate approach to categorizing data from an epidemiological perspective.

Adolescent↗

Favourable outcome for patients with myeloid disorders treated with fludarabine-melphalan reduced-intensity conditioning and allogeneic bone marrow stem cell transplantation without the use of T-lymphocyte-depleting antibodies.

We report the use of reduced-intensity conditioning (RIC)-matched sibling allogeneic bone marrow stem cell transplantation as a method of establishing a graft-vs.-leukaemia (GvL) effect against myeloid disorders using a fludarabine-melphalan protocol without the use of T-lymphocyte-depleting antibodies. The 16 patients in this group had predominantly poor-risk acute myeloid leukaemia (AML) (n=10), AML/myelodysplasia (MDS) (n=2) and MDS (n=4). All but one patient achieved full haematopoietic engraftment. Thirteen of 16 patients are alive and in continued complete remission on completion of this study with a median follow-up of 426 d (range 83-1524). The actuarial 4 yr disease-free and overall survival is 79% for both. Only one patient relapsed following transplant, giving a relapse rate of 6% during the study period. The treatment-related mortality was 13% (n= 2). Overall, acute graft-vs.-host disease (GvHD) occurred in 53% (8/15), with acute GvHD grade II or above occurring in 47% (7/15). In the 13 evaluable patients, chronic GvHD occurred in 46% (6/13), with this being extensive in three patients. These results suggest that a GvL effect can be delivered against poor-risk myeloid disorders with a low non-relapse mortality using this fludarabine-melphalan RIC protocol.

Acute Disease↗

Responses to a fourth dose of Haemophilus influenzae type B conjugate vaccine in early life.

OBJECTIVE: To describe the immune response of preterm infants, with a reduced response to primary Haemophilus influenzae type B (Hib) immunisation, to a fourth dose of Hib conjugate vaccine given in early life. DESIGN: Prospective observational study. SETTING: Five Wessex Neonatal Units. PATIENTS: Infants born at < 32 weeks and immunised with three doses of combined acellular pertussis-Hib vaccine, with a Hib IgG geometric mean concentration (GMC) < 1.0 microg/ml after these primary immunisations. INTERVENTIONS: An additional fourth dose of Hib conjugate vaccine given before 1 year of age. Blood taken to assess Hib IgG concentration and avidity after immunisation. MAIN OUTCOME MEASURES: Hib IgG GMC and avidity index. RESULTS: Ninety six infants (mean gestational age at birth 29.1 weeks) received a fourth dose of Hib at a mean age of 7.8 months. Hib IgG GMC after the primary immunisations was 0.17 microg/ml (95% confidence interval (CI) 0.14 to 0.20) rising to 4.68 microg/ml (95% CI 3.36 to 6.57) after the fourth dose (p < 0.0001). The IgG response to the fourth dose correlated positively with the response after the primary immunisations (p < 0.001). Hib IgG geometric mean avidity index (GMAI) after the primary immunisations was 30.87 (95% CI 20.40 to 46.73). This increased to 124.73 (95% CI 109.93 to 141.51) after the fourth dose (p < 0.0001). CONCLUSION: Preterm infants with very low IgG responses to Hib after primary immunisations with a combined acellular pertussis-Hib vaccine mount a good response to a fourth dose of Hib. This study suggests that all infants will benefit from a fourth dose of Hib, regardless of the age at which it is given.

Haemophilus Infections↗

The epidemiology of subacute sclerosing panencephalitis in England and Wales 1990-2002.

AIM: To assess the impact of measles/mumps/rubella (MMR) vaccine on the epidemiology of subacute sclerosing panencephalitis (SSPE) in England and Wales. METHODS: Cases of SSPE resident in England and Wales with onset between 1990 and 2002 were reviewed. RESULTS: A total of 47 cases were identified, 31 male and 16 female. There was an average annual decline of 14% in SSPE onset over the period, consistent with the decline in notified measles over the last 20 years. A history of measles was present in 35 (median age 1.3 years), the most recent recorded date being 1994; the interval from measles to onset of SSPE ranged from 2.7 to 23.4 years. Four children with a history of receipt of a measles containing vaccine were reported not to have had measles; two of these cases had a brain biopsy, and nucleotide sequence data confirmed wild measles infection. Brain biopsy specimens from a further three cases with a history of measles, of whom two had also had a history of vaccination, showed wild-type strain. CONCLUSION: The prevention of endemic circulation of measles virus in England and Wales through the high coverage achieved with MMR vaccine, together with the measles/rubella vaccination campaign of 1994, has resulted in the near elimination of SSPE. However, the recent decline in MMR vaccine coverage, with the associated increase in localised measles outbreaks and cases in young infants, is of concern. It underlines the importance of maintaining high vaccine coverage in order to protect indirectly those most vulnerable to SSPE, namely infants too young to be vaccinated.

Adolescent↗

Serological surveillance of rubella in Europe: European Sero-Epidemiology Network (ESEN2).

Serological surveillance is an important resource to evaluate vaccine programmes, especially for diseases such as rubella, where a sub-optimal programme can lead to an increase in morbidity. A coordinated vaccine policy in Europe is needed and the aim of the European Sero-Epidemiology Network (ESEN2) is to standardise serological surveillance in 22 countries for eight diseases, including rubella.

Europe↗

Acellular pertussis vaccine given by accelerated schedule: response of preterm infants.

OBJECTIVE: To describe the immune response of preterm infants to a diphtheria/tetanus/three component acellular pertussis (DTaP) vaccine, under an accelerated schedule, and the effects of steroids on this response. To compare responses with those of term infants. DESIGN: Prospective observational study. SETTING: Five Wessex neonatal units; Hertfordshire immunisation clinics. PATIENTS: Infants born at < 32 weeks; term controls. INTERVENTIONS: DTaP-Haemophilus influenzae type b vaccine given at 2, 3, and 4 months. Blood taken to assess antibody responses to vaccines. MAIN OUTCOME MEASURES: IgG geometric mean concentrations (GMC) to vaccines. RESULTS: A total of 130 preterm (mean gestational age 29.1 weeks) and 54 term infants were recruited. After the third immunisation, preterm infants had similar GMCs to controls to diphtheria, tetanus, filamentous haemagglutinin (FHA), and pertactin (PRN), but a significantly lower GMC to pertussis toxin (PT). Responses to tetanus and PRN increased with age at the third immunisation, and those to tetanus, FHA, PRN, and PT increased with gestational age at birth. Response to tetanus correlated negatively with the number of doses of antenatal steroids received. There was no association between responses and postnatal steroids. CONCLUSION: When immunised with a combined acellular pertussis- H influenzae type b vaccine under an accelerated schedule, IgG GMC of preterm infants to PT was reduced. GMCs to tetanus, FHA, PRN, and PT increased with gestational age at birth, and GMCs to tetanus and PRN increased with age at the third immunisation. There is, however, no benefit in delaying immunisation. Anti-tetanus IgG decreased with increasing number of doses of antenatal steroids. There was no effect for postnatal steroids.

Age Factors↗

Immunity and exposure to hepatitis A virus in pre-adolescent children from a multi-ethnic inner city area.

Seroprevalence data among ethnic minority groups within England and Wales are rare. An opportunistic approach was taken to test residual oral fluid, collected from pre-adolescent school children from an ethnically diverse region of northwest England, for anti-hepatitis A virus (HAV) IgG. Individual data on ethnicity and country of birth were also available. Of the 257 children who consented to participate, 62% were of South Asian ethnic origin. The overall seroprevalence was 18.8%, higher than 13.1% reported from a recent population-based survey in England and Wales among a mainly Caucasian population of the same age. The only factor significantly associated with HAV seropositivity in a multivariable logistic regression model was birth of the child abroad. Association with the place of birth of the child, but not that of the parent indicates that infection within this group occurs mainly abroad. Larger studies among ethnic minority groups are needed to investigate this claim further.

Asia, Western↗

Sero-epidemiology of mumps in western Europe.

Six countries (Denmark, England and Wales, France, Germany, Italy and The Netherlands) conducted large serological surveys for mumps, in the mid-1990s, as part of the European Sero-Epidemiology Network (ESEN). The assay results were standardized and related to the schedules and coverage of the immunization programmes and the reported incidence of mumps. Low incidence of disease and few susceptibles amongst adolescents and young adults was observed in countries with high mumps vaccine coverage (e.g. The Netherlands). High disease incidence and large proportions of mumps virus antibody negative samples in adolescent and young adult age groups was noted in countries with poor vaccine coverage (e.g. Italy). The build-up of susceptibles in older children and adolescents in England and Wales, France, the former West Germany and Italy indicate the possibility of further mumps outbreaks in secondary school environments. To control mumps in western Europe, current MMR immunization programmes will need to be strengthened in a number of countries. Sero-surveillance of mumps is an important component of disease control and its usefulness will be enhanced by the development of an international mumps standard.

Adolescent↗

Measurement and interpretation of pneumococcal IgG levels for clinical management.

The detection of pneumococcal IgG antibodies is helpful for the evaluation of response to pneumococcal vaccination and need for revaccination. Results generated by the clinical assay which is currently used, in which the 23 valent polysaccharide vaccine is the antigen, were compared to those obtained by a capsular polysaccharide serotype-specific assay that measures IgG antibodies to 9 common serotypes causing invasive disease. Discrepancies in 21/47 (45%) of the results were observed in a direct comparison between the two assays. In each case a positive titre was obtained on the clinical assay but IgG levels on the serotype-specific assay were below the putative protective level of 0.2 micro g/ml for at least one of the 9 serotypes assayed. The generation of false positives by the current clinical assay is due to its lack of specificity. Antibodies to C-polysaccharide and all of the 23 serotypes included in the pneumococcal polysaccharide vaccine are incorporated into the final titre whereas the serotype-specific assay adsorbs out noncapsular polysaccharide antibodies. The discrepancies between the two assays highlight the importance of standardized assays that measure putative correlates of protection and demonstrate the need to re-evaluate the current clinical assay. A tool that allows the interpretation of the results of the serotype-specific assay is provided and its potential for assessing individual susceptibility levels to vaccine preventable pneumococcal infection is discussed.

Adolescent↗

Bacterial infections, immune overload, and MMR vaccine. Measles, mumps, and rubella.

Combined measles, mumps, and rubella (MMR) vaccine did not increase the risk of hospitalisation with invasive bacterial infection in the three months after vaccination; rather there was a protective effect. These results provide no support for the concept of "immunological overload" induced by multiple antigen vaccinations, nor calls for single antigen vaccines.

Bacterial Infections↗

Prevalence of autism and parentally reported triggers in a north east London population.

BACKGROUND: The recorded prevalence of autistic spectrum disorders has risen over recent decades. Measles, mumps and rubella (MMR) vaccine has been blamed, by causing a "new variant" form of "regressive autism" associated with "autistic enterocolitis". AIMS: To estimate the prevalence of autism and to assess any changes in parental perception regarding the onset or causes of autism. METHODS AND RESULTS: A total of 567 children with autistic spectrum disorder in five districts in north east London were identified, born 1979-98. Reported autism, excluding the 94 cases of Asperger's syndrome, increased by year of birth until 1992, since when prevalence has plateaued. This flattening off persisted after allowing for expected delay in diagnosis in more recent birth cohorts. The age at diagnosis of autistic spectrum disorder was estimated to have decreased per five year period since 1983, by 8.7% for childhood autism and by 11.0% for atypical autism. There was some evidence that MMR was more likely to be mentioned as a trigger after August 1997 than before. CONCLUSIONS: The prevalence of autism, which was apparently rising from 1979 to 1992, reached a plateau from 1992 to 1996 at a rate of some 2.6 per 1000 live births. This levelling off, together with the reducing age at diagnosis, suggests that the earlier recorded rise in prevalence was not a real increase but was likely due to factors such as increased recognition, a greater willingness on the part of educationalists and families to accept the diagnostic label, and better recording systems. The proportion of parents attributing their child's autism to MMR appears to have increased since August 1997.

Adolescent↗

Severe and unrecognised: pertussis in UK infants.

AIMS: To diagnose pertussis using culture, polymerase chain reaction, and serology, in children admitted to intensive care units (PICUs) and some paediatric wards in London, and in their household contacts to determine the source of infection. METHODS: Infants <5 months old admitted to London PICUs between 1998 and 2000 with respiratory failure, apnoea and/or bradycardia, or acute life threatening episodes (ALTE), and children <15 years admitted to paediatric wards at St Mary's and St George's Hospitals between 1999 and 2000 with lower respiratory tract infection, apnoea, or ALTE were studied. RESULTS: Sixty seven per cent of eligible children (142/212) were recruited; 23% (33/142) had pertussis, 19.8% (25/126) on the PICU and 50% (8/16) on wards. Two died. Only 4% (6/142) were culture positive. Pertussis was clinically suspected on admission in 28% of infants (7/25) on the PICU and 75% (6/8) on the wards. Infants on PICU with pertussis coughed for longer, had apnoeas and whooped more often, and a higher lymphocyte count than infants without pertussis. Pertussis and respiratory syncytial virus (RSV) co-infection was frequent (11/33, 33%). Pertussis was confirmed in 22/33 (67%) of those who were first to become ill in the family. For 14/33 children the source of infection was a parent; for 9/33 the source of pertussis was an older fully vaccinated child in the household. CONCLUSIONS: Severe pertussis is under diagnosed. An RSV diagnosis does not exclude pertussis. Future changes to the UK vaccination programme should aim to reduce pertussis transmission to young infants by their parents and older siblings.

Anti-Bacterial Agents↗

Nutrient removal from wastewaters using high performance materials.

Return side streams from anaerobic digesters and dewatering facilities at wastewater treatment plants (WWTPs) contribute a significant proportion of the total nitrogen load on a mainstream process. Similarly, significant phosphate loads are also recirculated in biological nutrient removal (BNR) wastewater treatment plants. Ion exchange using a new material, known by the name MesoLite, shows strong potential for the removal of ammonia from these side streams and an opportunity to concurrently reduce phosphate levels. A pilot plant was designed and operated for several months on an ammonia rich centrate from a dewatering centrifuge at the Oxley Creek WWTP, Brisbane, Australia. The system operated with a detention time in the order of one hour and was operated for between 12 and 24 hours prior to regeneration with a sodium rich solution. The same pilot plant was used to demonstrate removal of phosphate from an abattoir wastewater stream at similar flow rates. Using MesoLite materials, >90% reduction of ammonia was achieved in the centrate side stream. A full-scale process would reduce the total nitrogen load at the Oxley Creek WWTP by at least 18%. This reduction in nitrogen load consequently improves the TKN/COD ratio of the influent and enhances the nitrogen removal performance of the biological nutrient removal process.

Aluminum Silicates↗

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↗

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↗

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↗