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Biomedical subjects

E Miller

Publications and source records attributed to E Miller.

At least 55 records · Page 3Linked to original sources

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↗

Oral fluid collection by post--a pilot study of two approaches.

This pilot study aimed to assess the feasibility of the postal collection of oral fluid samples for surveillance purposes and the effect of two different approaches on the response rates. This cross-sectional, antibody prevalence study collected oral fluid samples and questionnaire data from randomly selected individuals, aged under 45 y, through the post. The individuals were recruited from four general practice registers. In a one stage approach patients were sent the oral fluid kit with the initial invitation letter. In a two stage approach the kits were sent out after written consent had been received. There was little difference in the overall response rates between the two approaches (38% two stage and 41% one stage), though the response rate for the one stage approach was 10% higher in the under-20-y-olds in practices from areas of greater deprivation. The low response partly reflected poor uptake in young adults who may need to be approached through more targeted surveys. In the other age groups additional reminders could prove a cost-effective way of increasing the response rate further.

Adolescent↗

Characterization of measles virus strains causing SSPE: a study of 11 cases.

Eleven subacute sclerosing panencephalitis (SSPE) cases diagnosed in the UK between 1965 and 2000 were investigated. The entire or partial matrix (M), hemagglutinin (H), and nucleoprotein (N) genes of measles virus (MV) were sequenced following direct RT-PCR amplification from brain tissues. All the M genes showed the characteristic biased hypermutations and a premature termination codon was detected in 5/11 M sequences. Based on the more highly conserved H and N genes observed in persistent MV studies, phylogenetic analysis showed that two of three strains from patients likely to have acquired infection in the 1950s were related to clade C (WHO designation) and one appears to be a novel genotype. Three strains from patients infected in the 1960s and 1970s were clearly related to a MV strain isolated in 1974 belonging to genotype D1. Four strains from patients infected in the 1980s clustered with genotype D7 strains. One sequence from a patient infected in 1990s was identified as genotype D6. No vaccine strains were detected although five of these patients had been previously immunized. The sequence data obtained from these historic strains do not support the view that vaccine strains are associated with SSPE and provide valuable information for further studies of MV epidemiology, evolution, and pathogenesis in SSPE.

Adolescent↗

Vaccine programmes and policies.

Management of an effective national vaccine strategy necessitates careful planning. In the face of budgetary constraints and the likely development of many new vaccines over the next few years, a rational choice of which vaccines to use and how best to use them will depend on first class disease surveillance, economic analysis of cost effectiveness and mathematical modelling to ensure optimal vaccine delivery. Effective immunisation programmes require strategic planning that integrates the outputs of these parameters with available health facilities with the least possible disruption. At the present time, the greatest threat to vaccination is resistance to continuing vaccination in the face of declining prevalence of many infectious diseases and heightened fears over vaccine safety. Re-assurance of the public that vaccines are safe demands effective detection of vaccine-related side-effects and rigorous investigation of any safety concerns.

Health Planning↗

UK guidelines for use of erythromycin chemoprophylaxis in persons exposed to pertussis.

Pertussis is well controlled in the UK as a result of an effective vaccination programme. Nevertheless, the disease has not been eliminated, and cases still occur in the most vulnerable group of young infants. Erythromycin chemoprophylaxis has been advocated for use in contacts to prevent secondary cases but the evidence for its use is weak. These guidelines are based on a review of the evidence and aim to help clinicians make more rational decisions on the use of erythromycin chemoprophylaxis for pertussis. Erythromycin has well-established side effects and so its use should be limited to situations where it is likely to be of greatest benefit. If a clinically suspected or confirmed case of pertussis is identified who is also in household contact with someone at greatest risk from pertussis--young infants, especially neonates--then erythromycin chemoprophylaxis should be considered. The aim is to protect those at greatest risk from pertussis by offering chemoprophylaxis to them, to all their household contacts who are unimmunized and to contacts who are 5 years or older if they did not receive a pre-school pertussis booster (not given to those born before 1996 in the United Kingdom). There is no evidence of any benefit from chemoprophylaxis given more than 21 days from the date of onset of the primary case. Unimmunized or partially immunized cases and contacts should complete their course of vaccine.

Antibiotic Prophylaxis↗

Impact of meningococcal C conjugate vaccine in the UK.

This review details the impact of the introduction of meningococcal serogroup C conjugate (MCC) vaccines in the UK. An overall reduction of 86.7% in the incidence of serogroup C infection in the targeted age groups has been observed from 1999 to 2001, with a concomitant decrease in deaths, from 67 in 1999 to 5 in 2001. The enhanced surveillance programme initiated to complement the introduction of MCC vaccines has been essential in generating data relating to vaccine coverage, vaccine failures and efficacy estimates. Vaccine coverage has exceeded 80% in all age groups targeted and up to the end of 2001, 25 confirmed and 1 probable vaccine failure have been observed in England and Wales. Efficacy estimates for England up to September 2001 were 91.5% in infants receiving three doses of MCC vaccine and 89.3% in toddlers receiving one dose of MCC vaccine (England). There is some evidence of herd immunity in unvaccinated cohorts of the target age groups, ranging from a reduction in disease incidence of 34% in 9-14 year olds to 61% in 15-17 year olds. Surveillance of the genotypic and phenotypic characteristics of invasive and carriage isolates has shown no evidence to date of capsular switching from serogroup C to serogroup B.

Adolescent↗

Deaths from pertussis are underestimated in England.

AIMS: To improve estimates of deaths from pertussis in England and to identify reasons for under ascertainment. METHODS: Comparison of deaths identified from enhanced laboratory pertussis surveillance, hospital episode statistics (HES), and Office for National Statistics (ONS) death registrations in England, 1994 to 1999. RESULTS: A total of 33 deaths were identified, 88% of infants less than 4 months old. There was overlap between all sources; 22 deaths were identified in the enhanced pertussis surveillance system, 18 in ONS mortality data, and nine in HES. Children who had died from pertussis without mention of pertussis on the death certificate were more likely to have been certified by coroners than those with mention of pertussis (p = 0.0005). Using capture-recapture analysis, the total number of deaths from pertussis in the five and a half year period is estimated to be 46 (95% CI 37 to 71), or around nine deaths per year. CONCLUSIONS: National mortality statistics significantly under estimate deaths from pertussis in England and are inadequate for monitoring the national immunisation programme. The largest number of deaths is identified through enhanced laboratory surveillance. Death registration systems should take into account available microbiological information to ensure that cause of death is accurately assigned.

Cause of Death↗

Recall bias, MMR, and autism.

Parents of autistic children with regressive symptoms who were diagnosed after the publicity alleging a link with measles, mumps, and rubella (MMR) vaccine tended to recall the onset as shortly after MMR more often than parents of similar children who were diagnosed prior to the publicity. This is consistent with the recall bias expected under such circumstances.

Attitude to Health↗

Immune response of premature infants to meningococcal serogroup C and combined diphtheria-tetanus toxoids-acellular pertussis-Haemophilus influenzae type b conjugate vaccines.

To determine the immune response of premature infants to meningococcal serogroup C capsular polysaccharide (MCC) and combined diphtheria-tetanus toxoids-acellular pertussis-Haemophilus influenzae type b (DTaP-Hib) conjugate vaccines, 105 infants born at <32 weeks' gestation had Hib IgG geometric mean concentrations (GMCs) and MCC serum bactericidal antibody (SBA) geometric mean titers (GMTs) measured 1 month after the third immunization. Term infants served as control subjects. Premature infants had Hib GMCs of 0.27 microg/mL, with 21% achieving GMCs >1.0 microg/mL, compared with 0.81 microg/mL and 46% in term infants (P<.001 and P=.003, respectively). The MCC SBA GMT was 398, with 99% achieving an SBA > or =8, compared with 380 and 98% in term infants (P=.84 and P=1.0, respectively). Hib IgG was associated with age at third immunization (P<.001). When combined with the DTaP vaccine used in this study, the Hib GMC of premature infants was extremely low. The SBA GMT to MCC was similar to that of term infants.

Antibodies, Viral↗

Loss of dopamine transporters in methamphetamine abusers recovers with protracted abstinence.

Methamphetamine is a popular drug of abuse that is neurotoxic to dopamine (DA) terminals when administered to laboratory animals. Studies in methamphetamine abusers have also documented significant loss of DA transporters (used as markers of the DA terminal) that are associated with slower motor function and decreased memory. The extent to which the loss of DA transporters predisposes methamphetamine abusers to neurodegenerative disorders such as Parkinsonism is unclear and may depend in part on the degree of recovery. Here we assessed the effects of protracted abstinence on the loss of DA transporters in striatum, in methamphetamine abusers using positron emission tomography and [(11)C]d-threo-methylphenidate (DA transporter radioligand). Brain DA transporters in five methamphetamine abusers evaluated during short abstinence (<6 months) and then retested during protracted abstinence (12-17 months) showed significant increases with protracted abstinence (caudate, +19%; putamen, +16%). Although performance in some of the tests for which we observed an association with DA transporters showed some improvement, this effect was not significant. The DA transporter increases with abstinence could indicate that methamphetamine-induced DA transporter loss reflects temporary adaptive changes (i.e., downregulation), that the loss reflects DA terminal damage but that terminals can recover, or that remaining viable terminals increase synaptic arborization. Because neuropsychological tests did not improve to the same extent, this suggests that the increase of the DA transporters was not sufficient for complete function recovery. These findings have treatment implications because they suggest that protracted abstinence may reverse some of methamphetamine-induced alterations in brain DA terminals.

Adult↗

Planning, registration, and implementation of an immunisation campaign against meningococcal serogroup C disease in the UK: a success story.

The introduction of meningococcal C conjugate (MCC) vaccine in the UK in November 1999 as a routine 3 dose infant immunisation course, with a single catch-up dose for all children aged between 12 months and 17 years, was the result of an intensive 5 year collaborative research programme funded by the Department of Health for England and involving public bodies, academia and vaccine manufacturers. The research programme established the safety and immunogenicity of MCC vaccines in infants, toddlers, pre-school and school-aged children. The nature and frequency of common adverse events in school-aged children was similar to that after a booster dose of diphtheria and tetanus vaccine given to the same age groups. The recommendation that a single dose was adequate for children aged 12 months and above was based on antibody levels measured by serum bactericidal assay and evidence of induction of immunological memory as shown by maturation of antibody avidity. Licensure by the Medicines Control Agency was based on serological criteria alone without direct evidence of efficacy and has set a precedent for other meningococcal conjugate polysaccharide vaccines. Vaccine coverage of around 85% was achieved in the targeted age groups and has resulted in a drop in the incidence of serogroup C disease in these groups of over 80% within 18 months of the start of the vaccination programme. Early post-licensure efficacy estimates for toddlers and teenagers (88 and 96%, respectively, in the first 16 months after vaccination) validate the serological criteria used for licensure. Surveillance of the prevalent serogroups and serosubtypes among invasive case isolates has shown no evidence of any capsular switching to serogroup B during the first 18 months of the MCC vaccination programme.

Humans↗

Immunogenicity and reactogenicity of acellular diphtheria/tetanus/pertussis vaccines given as a pre-school booster: effect of simultaneous administration of MMR.

Four acellular diphtheria/tetanus/pertussis (aDTP) vaccines were compared with two diphtheria/tetanus (DT) vaccines given as a pre-school booster to 1033 children aged 4 to < 6 years who had completed primary immunisation with DTP vaccine according to the UK 2, 3 and 4 month schedule; 71 children had received aDTP vaccine and the remaining 962 a whole cell DTP vaccine for primary immunisation. The effect of simultaneous administration of a second dose of MMR vaccine was evaluated in 374 (37%). Overall, there was little difference in the frequency of post-vaccination symptoms in DT and aDTP vaccinees, although local reactions occurred more quickly in the aDTP group. The concomitant administration of MMR had no effect on local reactions or fever within 10 days, or on the proportions requiring a doctor's visit in the 4--6 week post-vaccination period. Local reactions > or = 3 cm were higher on day 2 in children who had received aDTP for primary immunisation (erythema 32.4% vs. 17.4% for wDTP, P = 0.0012; swelling 28.2% vs. 15.5%, P = 0.0027). Pertussis antibody responses were consistent with the antigen content of the aDTP vaccines. All were more immunogenic with respect to PT -- the only pertussis antigen which by itself has been shown to be protective in clinical trials -- than a wDTP pre-school booster given in an earlier trial. MMR vaccine had no significant effect on antibody responses to either the pertussis or diphtheria and tetanus antigens. Diphtheria antibody responses in children who had received wDTP for primary immunisation were 2.8 times higher than in those who had received aDTP vaccine (P < 0.0001); they were also higher in children who had received a single dose of a Haemophilus influenzae type b vaccine containing CRM(197) conjugate after 12 months of age. For countries currently using DT vaccines as a pre-school booster, replacement with an aDTP vaccine is unlikely to have a perceptible effect on reactogenicity, at least in children given wDTP for primary immunisation, and would boost antibody levels to antigens known to be associated with protection.

Child, Preschool↗

Influence of prior meningococcal C polysaccharide vaccination on the response and generation of memory after meningococcal C conjugate vaccination in young children.

To determine whether the immunological hyporesponsiveness induced by meningococcal AC polysaccharide (MACP) vaccines can be overcome by meningococcal C conjugate (MCC) vaccine in young children, serum bactericidal antibody (SBA) serogroup C-specific IgG and IgG avidity indices were measured in young children who received MACP vaccine, followed 7 months later by MCC vaccine, and their responses were compared with those in age-matched MACP-naive control children, who received a single dose of MCC vaccine. For children <1 year of age at MACP vaccination, the SBA geometric mean titer (GMT) after MCC vaccination was lower (P=.022) and proportions with SBA titers <8 (P=.0083) or <128 (P=.0091) were higher than those in the control children. For older children, there was no difference in the SBA GMTs between the study and control groups (P>.5) or in the proportion with SBA titers <8 (P=1.00) or <128 (P=.98). No increase in avidity occurred after MACP vaccination, whereas avidity increased significantly 1 month after MCC vaccination, with a further increase at 6 months, which indicates that the induction of immunological memory was not impaired.

Age Factors↗