PubMed Health⌕ Search

Biomedical subjects

Elizabeth Miller

Publications and source records attributed to Elizabeth Miller.

At least 19 recordsLinked to original sources
PubMed2006

Reactogenicity of meningococcal C conjugate vaccines when administered at the same time as, or a month prior to or after, tetanus and diphtheria booster vaccinations.

INTRODUCTION: This single blind study was conducted to address safety concerns regarding coadministration of diphtheria/ tetanus (DT,Td) boosters and meningococcal C conjugate (MCC) vaccines containing diphtheria or tetanus conjugate proteins. METHODS: 1754 subjects (835 preschoolers and 919 school leavers) were randomised to receive one of three MCC products a month before, after or at the same as routine DT or Td boosters. They (or their parents) completed a health diary for 10 days to record local reactions and systemic symptoms after each vaccination. The effect of antibody levels pre and post-vaccination, preexisting allergies and medication taken before and for up to ten days after vaccination on reactogenicity was assessed. RESULTS: No relationship between prevaccination antibody levels and local reactions or systemic symptoms was found. Local reactions were more common after DT/Td than MCC vaccination and were related to post-vaccination diphtheria and tetanus antibody levels in younger children and to the post-vaccination tetanus only antibody levels in older children. Preexisting allergies were not related to reactogenicity. Use of analgesics/antipyretic medication significantly reduced the incidence of local reactions and of some systemic symptoms. In the first three days after vaccination there was an excess of some systemic symptoms including fatigue/malaise and headache for all ages, and crying/ irritability for younger children and nausea/vomiting and dizziness/faintness for older subjects. Eleven serious adverse events were reported, none of which was deemed related to vaccination. CONCLUSION: MCC vaccines can be given under the above schedules and safely in the presence of raised diphtheria and tetanus antibody levels without materially altering reactogenicity profiles of either vaccine.

Adolescent↗
PubMed2006

Clinical and immunologic risk factors for meningococcal C conjugate vaccine failure in the United Kingdom.

BACKGROUND: The meningococcal serogroup C conjugate (MCC) vaccine was introduced into the United Kingdom with licensure based on immunogenicity data not efficacy data. METHODS: All subjects with laboratory-confirmed meningococcal serogroup C (MenC) disease from January 2000 to December 2003 in England and Wales were followed up. A vaccine failure was defined as a laboratory-confirmed case of MenC disease occurring > or =10 days after the subject's last scheduled dose of MCC vaccine. Total immunoglobulins, serum bactericidal antibody (SBA) titers, MCC anticapsular antibody levels, and avidity indices (AIs) were measured in acute and convalescent serum samples from subjects with vaccine failure and unvaccinated subjects with MenC disease. RESULTS: Of 465 subjects with confirmed MenC disease identified among those eligible for vaccination, information on vaccination history was obtained for 462 (99.4%); of these, 53 were subjects with vaccine failure. SBA titers in convalescent serum samples and AIs in acute serum samples were significantly higher in subjects with vaccine failure than in unvaccinated subjects, (6.1-fold higher for SBA titers [P=.03] and 3.2-fold higher for AIs [P=.001]). CONCLUSIONS: The antibody response in the subjects with vaccine failure was consistent with an anamnestic response, suggesting that MenC disease occurred despite the MCC vaccine priming for immune memory. Persistence of antibodies may be a more appropriate correlate of long-term protection for MCC vaccines than the ability to generate a booster response on exposure.

Adolescent↗
PubMed2006

Pneumococcal polysaccharide vaccine uptake in England, 1989-2003, prior to the introduction of a vaccination programme for older adults.

OBJECTIVE: Following the licensure of 23-valent pneumococcal polysaccharide vaccine (23vPPV) in 1989, a risk-group-only immunization policy was implemented in 1992 in England. The PPV programme was extended in 2003 to include all individuals 65 years and over. In England, this was phased in over 3 years. To ascertain the performance of the risk group policy in those 65 years of age and over and provide a baseline to estimate the impact of the universal elderly programme. METHODS: Information was gathered on vaccine uptake for the period 1989-2003 in England from a national survey of general practitioners (GPs) through NHS primary care trusts (PCTs), the prescription cost analysis (PCA) system and the General Practice Research Database (GPRD). RESULTS: Between 1991 and 2003, 4.5 million doses of PPV were prescribed. The GP survey found that by 2003, 29% of those 65 years and over of age and 36% of those 80 years of age over had received PPV. Sixty-two per cent of general practices had implemented a risk-group-only policy, 14.4% had targeted all those 65 years of age over and 14.2% had targeted all those 75 years of age over. The GPRD study found that 38% of those 65 years over and 41% of those 80 years over fell into one or more high-risk groups. By 2003, 36.6% of the high-risk group and 30.2% of all those 65 years over had ever been vaccinated. Vaccine uptake increased with age, with 52.3% of the high-risk group and 37% of all those 80 years over having ever been vaccinated. CONCLUSIONS: A large proportion of those in risk groups remained unvaccinated with PPV in 2003. Formal evaluation of the impact and effectiveness of the universal elderly immunization programme will be required.

Aged↗
PubMed2006

Oxidized low-density lipoprotein autoantibodies, chronic infections, and carotid atherosclerosis in a population-based study.

OBJECTIVES: We investigated whether associations exist between immune reactions to oxidized low-density lipoproteins (OxLDLs), chronic infections, and carotid atherosclerosis as quantified by ultrasound. BACKGROUND: Atherosclerosis is a chronic immuno-inflammatory disease wherein both oxidized lipids and infectious agents are incriminated as possible contributors. METHODS: We measured immunoglobulin (Ig)G and IgM autoantibody titers to copper-oxidized-LDL and malondialdehyde-LDL (OxLDL-AB), IgG and IgM apolipoprotein B-100-immune complexes (ApoB-IC), and titers of antibodies to Escherichia coli and chlamydial lipopolysaccharide (LPS), mycobacterial heat shock protein 65 (mHSP65), Chlamydia pneumoniae, Helicobacter pylori, and cytomegalovirus and evaluated their relationship to cardiovascular risk factors, chronic infections, and incident/progressive carotid atherosclerosis in the Bruneck study. RESULTS: The OxLDL-AB and ApoB-IC levels remained stable over time as indicated by strong correlations between 1995 and 2000 measurements (p < 0.001 each). Significant associations existed between all OxLDL markers and antibody titers to pathogens, especially to E. coli-LPS and mHSP65. Both OxLDL-AB and ApoB-IC levels showed a rise with increasing pathogen burden. Notably, OxLDL-ABs were also elevated in subjects with chronic infection as defined by clinical criteria. Titers of IgG, but not IgM, OxLDL-AB, or ApoB-IC inversely correlated with total cholesterol, LDL cholesterol, and apoB concentrations. The IgG OxLDL markers were positively and IgM markers were inversely associated with incident and progressive carotid atherosclerosis in univariate analyses but were not independent predictors in multivariate analyses. CONCLUSIONS: Our study provides evidence for an association between human oxLDL markers and chronic infections. Moreover, in this population-based study, neither IgG nor IgM OxLDL autoantibodies were independently predictive of atherosclerosis progression in the carotid arteries.

Adult↗
PubMed2006

Bell's palsy and parenteral inactivated influenza vaccine.

Concern about a possible increased risk of Bell's palsy after parenteral inactivated influenza vaccine was raised following the publication in 2004 of a Swiss study in which there was an increased risk following the nasal inactivated formulation of the vaccine. When data from passive reporting systems in the United States and the United Kingdom were examined there was some evidence of increased reporting following the parenteral vaccine. A large population based study using the General Practice Research Database (GPRD) was therefore performed to test the hypothesis that there was an increased risk of Bell's palsy in the three months following parenteral inactivated influenza vaccine. The risk was also assessed for the same period following pneumococcal vaccine and was stratified into three age groups (<45, 45-64 and 65+ years). Relative incidence (RI) estimates were calculated using the self-controlled case-series method and showed no evidence of an increased risk in the three months following parenteral inactivated influenza vaccine RI 0.92 (95% confidence interval 0.78-1.08). There was also no evidence of an increased risk in any age group or following pneumococcal vaccine. A significant increase was seen on the day of vaccination (day 0) probably due to opportunistic recording of cases.

Adolescent↗
PubMed2006

Modeling future changes to the meningococcal serogroup C conjugate (MCC) vaccine program in England and Wales.

The UK meningococcal serogroup C conjugate (MCC) vaccine program has successfully controlled serogroup C disease, due to high vaccine effectiveness and substantial herd immunity. However, children immunised at 2, 3 and 4 months of age receive only short-term direct protection and may be at risk of disease 15 months after vaccination. To investigate this we applied a mathematical model to predict the future epidemiology of serogroup C disease, with and without changes to the immunization schedule. Only a few cases of serogroup C disease were predicted to occur over the next few years because of persisting herd immunity, even without a change to the vaccine schedule. The inclusion of a booster dose is likely to improve the impact of the MCC program and reducing the number of doses in infancy will improve cost-effectiveness and create space in the schedule for the addition of other vaccines.

Adolescent↗
PubMed2006

A randomised controlled study of the reactogenicity of an acellular pertussis-containing pentavalent infant vaccine compared to a quadrivalent whole cell pertussis-containing vaccine and oral poliomyelitis vaccine, when given concurrently with meningococcal group C conjugate vaccine to healthy UK infants at 2, 3 and 4 months of age.

Two hundred forty-one healthy infants were enrolled in an open randomised controlled study of three doses of DTaP-IPV-Hib (Group 1) or DTwP/Hib+OPV (Group 2) at 2, 3 and 4 months of age given concurrently with a meningitis C conjugate vaccine. After each dose, local reactions (any grade) were less common in Group 1 than Group 2 (p<0.03). Axillary temperature >37.5 degrees C, decreased feeding, reduced activity, irritability and crying in the week after vaccination were also less common in Group 1 than Group 2 (p<0.05 for each symptom, all doses combined). Severe local reactions and systemic symptoms were uncommon and occurred equally in both groups. The pentavalent DTaP-IPV-Hib vaccine was less reactogenic than the quadrivalent DTwP-Hib vaccine, as expected when changing from whole cell pertussis (wP) to an acellular pertussis (aP) component.

Bacterial Vaccines↗
PubMed2006

Laboratory investigation of immune responses to acellular pertussis vaccines when used for boosting adolescents after primary immunisation with whole cell pertussis vaccines: a comparison with data from clinical study.

The lack of unequivocal immunological correlates of human protection and an absence of a validated animal model for acellular pertussis vaccines, compounded by limited opportunity to undertake efficacy studies in humans and laboratory evaluation side by side, has made it difficult to compare vaccines and formulations. In the present study, the effect on the booster response to pertussis in adolescents primed in infancy with whole cell pertussis vaccine, of three low dose acellular pertussis/diphtheria/tetanus toxoid (TdPa) formulations with or without inactivated poliomyelitis vaccine (IPV) components, was investigated. To assess the relationship between laboratory vaccine evaluation and clinical trial performance, parallel evaluation of the same TdPa vaccines were carried out in a mouse booster model with whole cell pertussis vaccine priming. Prior to boosting, the clinical subjects had low cell mediated immune responses (CMI) responses to pertussis vaccine components. After boosting, all TdPa formulations stimulated CMI responses to the pertussis vaccine components assessed. The booster responses to the pertussis antigens remained skewed towards Th1 type even though acellular pertussis vaccines were used. In general the antibody and CMI responses to pertussis antigens in the mouse model followed the trend seen in the human subjects. Protection against aerosol challenge with virulent Bordetella pertussis was related to the magnitude of the antibody and CMI responses in the mouse model. As in the human subjects, the responses remained skewed towards Th1 type.

Animals↗
PubMed2006

Social norms and beliefs regarding sexual risk and pregnancy involvement among adolescent males treated for dating violence perpetration.

The present study explored perceived sexual norms and behaviors related to sexual risk and pregnancy involvement among adolescent males (ages 13 to 20) participating in programs for perpetrators of dating violence. The purpose of this study was to generate hypotheses regarding the contexts and mechanisms underlying the intersection of adolescent dating violence, sexual risk and pregnancy. Six focus groups were conducted (N = 34 participants). A number of major themes emerged: 1) male norm of multiple partnering, 2) perceived gain of male social status from claims of sexual activity, 3) perception that rape is uncommon combined with belief that girls claiming to be raped are liars, 4) perception that men rationalize rapes to avoid responsibility, 5) condom non-use in the context of rape and sex involving substance use, 6) beliefs that girls lie and manipulate boys in order to become pregnant and trap them into relationships, and 7) male avoidance of responsibility and negative responses to pregnancy. The combination of peer-supported norms of male multiple partnering and adversarial sexual beliefs appear to support increased male sexual risk, lack of accountability for sexual risk, and rationalization of rape and negative responses to pregnancy. Further research focused on the context of male sexual risk and abusive relationship behaviors is needed to inform intervention with young men to promote sexual health and prevent rape, dating violence, and adolescent pregnancy.

Adolescent↗
PubMed2006

Immunogenicity and boosting after a reduced number of doses of a pneumococcal conjugate vaccine in infants and toddlers.

BACKGROUND: The minimum number of doses of pneumococcal conjugate vaccine required for protection is not known. We studied the immunogenicity of a reduced schedule in infants and toddlers. METHODS: U.K. infants were given either 2 or 3 doses (at 2 and 4 or 2/3/4 months of age) of a 9-valent pneumococcal conjugate vaccine (9VPCV) followed by boosting at 12 months of age. In a separate study, toddlers (12 months) received 1 or 2 doses (2 months apart) of 9VPCV followed by pneumococcal polysaccharide vaccine at 18 months of age. RESULTS: For infants, serotype-specific IgG geometric mean concentrations were similar post-primary immunization between the groups with both showing avidity maturation and similar booster responses. For toddlers, the primary response to 4 of the 9 serotypes was lower in the 1- compared with the 2-dose group (type 6B, 0.77 versus 7.1; type 14, 4.67 versus 14.98; type 19F, 5.05 versus 7.75; type 23F, 2.48 versus 5.05), although for all serotypes booster responses were similar between groups, and the postprimary responses in the 1-dose group were at least as high as those after infant immunization. CONCLUSIONS: The 2-dose infant priming schedule of 9VPCV is comparable with the 3-dose schedule and may thus be equally protective, whereas 1 dose in toddlers may suffice for a catch-up.

Antibodies, Bacterial↗
PubMed2006

Internal medicine residents' perceptions of cross-cultural training. Barriers, needs, and educational recommendations.

BACKGROUND: Physicians increasingly face the challenge of managing clinical encounters with patients from a range of cultural backgrounds. Despite widespread interest in cross-cultural care, little is known about resident physicians' perceptions of what will best enable them to provide quality care to diverse patient populations. OBJECTIVES: To assess medicine residents' (1) perceptions of cross-cultural care, (2) barriers to care, and (3) training experiences and recommendations. DESIGN, SETTING, AND PATIENTS: Qualitative individual interviews were conducted with 26 third-year medicine residents at Massachusetts General Hospital in Boston (response rate=87%). Interviews were recorded, transcribed, and analyzed. RESULTS: Despite significant interest in cross-cultural care, almost all of the residents reported very little training during residency. Most had gained cross-cultural skills through informal learning. A few were skeptical about formal training, and some expressed concern that it is impossible to understand every culture. Challenges to the delivery of cross-cultural care included managing patients with limited English proficiency, who involve family in critical decision making, and who have beliefs about disease that vary from the biomedical model. Residents cited many implications to these barriers, ranging from negatively impacting the patient-physician relationship to compromised care. Training recommendations included making changes to the educational climate and informal and formal training mechanisms. CONCLUSIONS: If cross-cultural education is to be successful, it must take into account residents' perspectives and be focused on overcoming residents' cited barriers. It is important to convey that cross-cultural education is a set of skills that can be taught and applied, in a time-efficient manner, rather than requiring an insurmountable knowledge base.

Attitude of Health Personnel↗
PubMed2006

Immunoglobulin G subclass response to a meningococcal quadrivalent polysaccharide-diphtheria toxoid conjugate vaccine.

Changes in the immunoglobulin G1 (IgG1)/IgG2 ratio following vaccination can indicate the activation of cellular control mechanisms typical of a T-cell-dependent response. We examined IgG subclass ratios in 17 healthy adults (26 to 55 years of age) before and 4 to 6 weeks following immunization with a quadrivalent meningococcal-polysaccharide diphtheria toxoid conjugate vaccine against serogroups A, C, Y, and W135. Serologic responses were determined by serum bactericidal antibody assay and serogroup-specific IgG, IgG1, and IgG2 enzyme-linked immunosorbent assay. Prevaccination serogroup A-specific IgG1/IgG2 ratios were <1 for all subjects and differed by subject for C, Y, and W-135. Postvaccination, significant increases in IgG, IgG1, and IgG2, were observed for all serogroups. Serogroup-specific IgG1/IgG2 ratios increased for group A (14/17 subjects, 88%), decreased in more than half of subjects for groups C (9/17, 53%) and W135 (12/17, 71%) and decreased for serogroup Y (16/17, 94%). IgG1/IgG2 ratios differed between individual vaccinees and were similar to the responses of adults who received pneumococcal conjugate vaccines or a monovalent C conjugate vaccine. Further studies on IgG subclasses following meningococcal polysaccharide and conjugate vaccination are needed.

Adult↗
PubMed2006

Comparison and correlation of neisseria meningitidis serogroup B immunologic assay results and human antibody responses following three doses of the Norwegian meningococcal outer membrane vesicle vaccine MenBvac.

The prediction of efficacy of Neisseria meningitidis serogroup B (MenB) vaccines is currently hindered due to the lack of an appropriate correlate of protection. For outer membrane vesicle (OMV) vaccines, immunogenicity has primarily been determined by the serum bactericidal antibody (SBA) assay and OMV enzyme-linked immunosorbent assay (ELISA). However, the opsonophagocytic assay (OPA), surface labeling assay, whole blood assay (WBA), and salivary antibody ELISA have been developed although correlation with protection is presently undetermined. Therefore, the aim of the study was to investigate further the usefulness of, and relationships between, MenB immunologic assays. A phase II trial of the OMV vaccine, MenBvac, with proven efficacy was initiated to compare immunologic assays incorporating the vaccine and six heterologous strains. Correlations were achieved between the SBA assay, OMV ELISA, and OPA using human polymorphonuclear leukocytes and human complement but not between an OPA using HL60 phagocytic cells and baby rabbit complement. Correlations between the surface labeling assay, the SBA assay, and the OMV ELISA were promising, although target strain dependent. Correlations between the salivary antibody ELISA and other assays were poor. Correlations to the WBA were prevented since many samples had results greater than the range of the assay. The study confirmed the immunogenicity and benefit of a third dose of MenBvac against the homologous vaccine strain using a variety of immunologic assays. These results emphasize the need for standardized methodologies that would allow a more robust comparison of assays between laboratories and promote their further evaluation as correlates of protection against MenB disease.

Adult↗
PubMed2006

Long-term protection in children with meningococcal C conjugate vaccination: lessons learned.

Owing to an increase in group C disease, extensive prelicensure studies have been funded by both the UK Department of Health and vaccine manufacturers. These demonstrated the safety and immunogenicity of three candidate meningococcal group C conjugate (MCC) vaccines (two conjugated to CRM(197) and one to tetanus toxoid) in the targeted age groups. Induction of immunological memory in infants and young children was also demonstrated by either a low dose of polysaccharide challenge following primary immunization with MCC or by an increase in avidity indices post-primary to pre-challenge. Immune memory after infant immunization persisted to at least 4 years of age, although antibody persistence in this age group was poor. MCC vaccine was introduced into the UK routine immunization schedule at 2, 3 and 4 months of age in 1999, with a catch-up as a single dose to all children aged 1-18 years with two doses for infants aged 5-11 months. The number of group C cases fell rapidly in the targeted age groups and early analyzes showed high vaccine effectiveness in all age groups together with significant herd immunity. However, when effectiveness was measured again more than 1 year after vaccination, there was a significant decline in all age groups, most marked in infants vaccinated in the routine infant immunization program, for whom there was no demonstrable efficacy after only 1 year and then in toddlers for whom efficacy declined to 61% (95% confidence interval: -327-94) from 88% (95% confidence interval: 65-96) in the first year. However, good disease control was maintained in the UK with only low numbers of vaccine failures. The assumption that immune memory was predictive of long-term protection is incorrect, at least after vaccination in infancy. Persistence of antibody and herd immunity may be more relevant for long-term disease control.

Child↗
PubMed2005

Antibody responses to nasopharyngeal carriage of Streptococcus pneumoniae in adults: a longitudinal household study.

BACKGROUND: Natural immunity to Streptococcus pneumoniae is thought to be induced by exposure to S. pneumoniae or cross-reactive antigens. No longitudinal studies of carriage of and immune responses to S. pneumoniae have been conducted using sophisticated immunological laboratory techniques. METHODS: We enrolled 121 families with young children into this study. Nasopharyngeal (NP) swabs were collected monthly for 10 months from all family members and were cultured in a standard fashion. Cultured S. pneumoniae isolates were serotyped. At the beginning (month 0) and end (month 10) of the study, venous blood was collected from family members >18 years old. Serotype-specific antipolysaccharide immunoglobulin G (IgG) and functional antibody and antibodies to pneumolysin, pneumococcal surface protein A (PspA), and pneumococcal surface antigen A (PsaA) were measured in paired serum samples. RESULTS: Levels of anticapsular IgG increased significantly after carriage of serotypes 9V, 14, 18C, 19F, and 23F by an individual or family member. For serotype 14, a higher level of anticapsular IgG at the beginning of the study was associated with reduced odds of carriage (P = .006). There was a small (approximately 20%) but significant increase in titers of antibodies to PsaA and pneumolysin but no change in titers of antibody to PspA. CONCLUSIONS: Adults respond to NP carriage by mounting anticapsular and weak antiprotein antibody responses, and naturally induced anticapsular IgG can prevent carriage.

Adult↗
PubMed2005

Reactions to small pox vaccine in naïve and previously-vaccinated individuals.

Two hundred health care workers in England and Wales were vaccinated with the Lister/Elstree strain of the vaccinia virus, and completed health diaries for 21 days or until the lesion had scabbed over. Pain and temperature were measured daily, and all other symptoms recorded freehand by the vaccinee. One hundred and forty two (71%) vaccinees reported pain, of which 25% considered it to be moderate or severe; 32 vaccinees (16%) recorded a temperature of >37.7 degrees C, two of which exceeded 39 degrees C. Other, mainly trivial, adverse events were common; itch was reported in 72%, erythema in 27%, axillary pain or lymphadenopathy in 38%, malaise or flu-like symptoms in 40% and headache in 23%. The incidences of minor adverse events were lower in re-vaccinees, compared with naïve vaccine recipients, significantly so in the case of erythema and general malaise (p=0.001 and 0.006, respectively), perhaps reflecting pre-existing immunity. Major adverse events occurred in two vaccinees (hospital admission, one with cellulitis and one with headache and possible encephalitis), and a further five were treated with antibiotics for local cellulitis. This is the first study to report results derived from active follow-up by diaries in recipients of the Lister/Elstree strain of vaccinia, and to document reductions in trivial adverse events in re-vaccinees.

Adverse Drug Reaction Reporting Systems↗
PubMed2005

Immunogenicity and reactogenicity of combined acellular pertussis/tetanus/low dose diphtheria vaccines given as a booster to UK teenagers.

Sustained high incidence of pertussis, particularly amongst unvaccinated infants, is of concern. Inclusion of pertussis vaccination with tetanus and low dose diphtheria (Td) teenage boosters may protect individuals through reproductive years, and prevent transmission to offspring. UK teenagers who had previously received only a three-dose primary course of whole cell pertussis vaccination in infancy and who were due to receive a Td booster (n=323) were randomised to four groups: Td, TdaP, TdaP-inactivated polio vaccine (IPV) (Aventis Pasteur), TdaP (GlaxoSmithKline). There were significant pre- to post-vaccination GMC and GMFR increase for vaccine-contained pertussis antigens (p<0.001) in recipients of aP-containing vaccine. All groups demonstrated significant increases pre- to 4 weeks post-vaccination in diphtheria (D)/tetanus (T) geometric mean concentrations (GMCs) and fold rises (GMFRs) (p<0.001). Groups all achieved similar D and T post-vaccination GMCs. Local reactogenicity was generally similar between groups and was not associated with pre-booster diphtheria/tetanus antibody levels. A minority of vaccinees reported systemic symptoms with similar proportions between groups for each symptom assessed. This study demonstrated that addition of aP and/or IPV to Td vaccine did not materially alter reactogenicity or immunogenicity of Td components, and induced immune responses to pertussis antigens in teenagers who had received no pertussis vaccine since infancy.

Adolescent↗