New combination vaccines still need a boost.
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Adolescent↗
Biomedical subjects
A J Pollard
Publications and source records attributed to A J Pollard.
Influence of genetic and environmental factors on the immunogenicity of Hib vaccine in Gambian twins.
The differences in incidence rates of Haemophilus influenzae type b disease and the variation in Hib conjugate vaccine efficacy achieved among different ethnic groups suggest genetic influences on the immune response to Hib vaccine. The serum anti-PRP antibody concentration of 43 monozygotic (MZ) and 147 dizygotic (DZ) twin pairs in the Gambia was measured using a standardised Hib ELISA. Intrapair correlations for MZ and DZ twin pairs were compared and heritability in antibody responses to Hib conjugate vaccine was estimated to be 51% (95% CI: 32-66%), indicating a significant genetic contribution in the response. We conclude that genetic factors may be involved in the variation in immune response to Hib vaccine observed in different populations and may contribute to cases of vaccine failure.
Antibodies, Bacterial↗
Osteomyelitis of the humerus complicating BCG vaccination.
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BCG Vaccine↗
Syphilis in pregnancy and the neonatal period.
The recent increase in the number of cases of syphilis in the UK, including among women of reproductive age, has stimulated the need for a review of practices concerning assessment and management of syphilis in pregnancy and the neonatal period. This paper summarizes available evidence from published guidelines, primary and secondary research. Optimal management of syphilis in pregnancy and the neonatal period relies on the early diagnosis and staging of maternal disease, prompt treatment to prevent congenital syphilis, and timely assessment of newborns.
Decision Trees↗
Parental views on the introduction of an infant pneumococcal vaccine.
Streptococcus pneumoniae is a major cause of early childhood morbidity and mortality. A heptavalent pneumococcal conjugate vaccine (PnC7) is licensed for use and could prevent the majority of infant invasive pneumococcal infections. A recent announcement confirmed its inclusion into the U.K. childhood immunisation programme. In anticipation of PnC7 being recommended for use, this study explored parental understanding of pneumococcal disease and their views on the possible introduction of this vaccine. Twenty three interviews and two focus groups were held with parents of children under two years of age. Four main themes emerged from the data analysis: 'Confidence and belief in immunisation'; 'Anxiety about immunisation'; 'Trust and understanding of immunisation information' and 'Response to a new immunisation'. Overall parental confidence in immunisation has been affected by the MMR controversy. With little knowledge of pneumococcal disease, parents want information about the safety and effectiveness of PnC7. Information needs to be conveyed in a way that restores parents' trust in immunisation.
Adult↗
Vaccines against bacterial meningitis.
Meningitis remains an important cause of morbidity and mortality among children >5 years of age and is especially prevalent in developing countries. Effective routine immunization against Hib, pneumococcus and serogroupC meningococcus has had a significant impact on both invasive disease and carriage caused by these encapsulated bacteria. The major challenge in prevention of meningitis remains the delivery of vaccines worldwide, especially to resource-poor regions with the greatest disease burden.
Bacterial Proteins↗
Immunogenicity and safety of a low-dose diphtheria, tetanus and acellular pertussis combination vaccine with either inactivated or oral polio vaccine as a pre-school booster in UK children.
This open, randomised controlled trial studied the immunogenicity and reactogenicity of two combined low-dose diphtheria, tetanus and acellular pertussis vaccines (Td5aP-IPV, REPEVAX, Aventis Pasteur MSD; and Td5aP, COVAXIS, Aventis Pasteur MSD + OPV, GlaxoSmithKline) in comparison with a standard dose diphtheria pre-school booster vaccine (DT2aP-IPV, TETRAVAC, Aventis Pasteur MSD) in a population of 3.5-5-year-old children administered concomitantly with measles, mumps and rubella vaccine (M-M-R II, Aventis Pasteur MSD). A linked sub-study aimed to evaluate the immunogenicity and reactogenicity of Td5aP-IPV in a population of younger children, aged 3-3.5 years. This study demonstrated non-inferiority of seroprotection rates for diphtheria and tetanus for the study vaccines and comparable immunogenicity for pertussis and polio components of the vaccines. Reactogenicity was similar for all three vaccines. The study vaccines containing low-dose diphtheria antigen (Td5aP-IPV and Td5aP + OPV) are immunogenic and have acceptable reactogenicity for use as a pre-school booster vaccine administered concomitantly with MMR.
Antitoxins↗
Twelfth nerve palsy due to a retropharyngeal tuberculous abscess.
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Antitubercular Agents↗
Clinical features of headache at altitude: a prospective study.
BACKGROUND: Headache is the most common nervous system complication at altitude; however, there have been few attempts to characterize clinical features of high-altitude headaches (HAH). OBJECTIVE: To measure prospectively the incidence of HAH and to determine its risk factors and characteristics. METHODS: Members of an expedition to Kanchenjunga base camp in Nepal (5,100 m) were prospectively studied. Subjects were interviewed prior to the trip and while trekking recorded headaches experienced at >3,000 m using a structured questionnaire incorporating International Headache Society (IHS) and acute mountain sickness (AMS) criteria. In addition, clinical features of headaches in 19 trekkers in other groups above 3,000 m were recorded using the same questionnaire. RESULTS: Eighty-three percent (50/60) reported at least 1 HAH (median 2, range 0 to 10). Those who developed HAH were younger (p = 0.04); women and persons with headaches in daily life were more likely to report severe headaches (p = 0.03 and p = 0.07). One hundred thirty-eight HAH, experienced by 69 persons, are described. The mean altitude at which headaches occurred was 4,723 m. Twenty-six percent of headaches woke subjects at night or occurred upon awakening. HAH reported by migraineurs were accompanied by more phonophobia (p = 0.008). There were no IHS accompanying symptoms in 44% of headaches or symptoms of AMS in 52% of headaches. CONCLUSIONS: Headaches are a frequent complication of ascent to altitude. Older age appears to offer some protection, whereas headaches were more severe in women and persons with headaches in daily life. There is a wide clinical spectrum, with some suggesting intracranial hypertension. There is a need for evidence-based diagnostic criteria for headaches at altitude.
Adaptation, Physiological↗
Immunologic memory in Haemophilus influenzae type b conjugate vaccine failure.
AIMS: To compare the convalescent antibody response to invasive Haemophilus influenzae type b (Hib) disease between conjugate vaccine immunised and unimmunised children, to look for evidence of priming for immunologic memory. METHODS: Unmatched case-control study in the UK and Eire 1992-2001 and Victoria, Australia 1988-1990. A total of 93 children were identified as having invasive Hib disease following three doses of conjugate vaccine in infancy through post licensure surveillance throughout the UK and Eire; 92 unvaccinated children admitted to an Australian paediatric hospital with invasive Hib disease were used as historical controls. Convalescent serum was taken for measurement of Hib antibody concentration, and clinical information relating to potential disease risk factors was collected. The geometric mean concentrations of convalescent Hib antibodies were compared between immunised and unimmunised children, using raw and adjusted data. RESULTS: Hib conjugate vaccine immunised children had higher serum Hib antibody responses to disease (geometric mean concentration (GMC) 10.81 microg/ml (95% CI 6.62 to 17.66) than unimmunised children (1.06 microg/ml (0.61 to 1.84)) (p < 0.0001). However, following adjustment for the significant confounding influences of age at presentation and timing of serum collection, a difference persisted only in children presenting with meningitis (vaccinated GMC 3.78 microg/ml (2.78 to 5.15); unvaccinated GMC 1.48 microg/ml (0.90 to 2.21); p = 0.003). CONCLUSIONS: Higher antibody responses to invasive Hib disease in vaccinated children with meningitis reflect priming for immunologic memory by the vaccine. Although a majority of children in the UK are protected from Hib disease by immunisation, the relative roles of immunologic memory and other immune mechanisms in conferring protection remain unclear.
Age Factors↗
The future of meningitis vaccines.
Without effective vaccines meningitis remains a substantial worldwide threat with major health-care implications. A number of advances have been made in vaccine design and implementation over the last decade, with new vaccine initiatives providing substantial promise for the future reduction of global disease burden.
Bacterial Capsules↗
Respiratory syncytial virus infections in children and adults.
Respiratory syncytial virus is the leading cause of hospital admission for lower respiratory tract infection in young children and appears to be responsible for a significant burden of disease in adults, particularly the elderly and the immunocompromised. In this review, we describe the epidemiology, diagnosis and clinical manifestations of infection attributed to this virus. We also consider current therapeutic and prophylactic options and appraise strategies for vaccination that are in clinical trials.
Adult↗
Pelvic inflammatory disease associated with Enterobius vermicularis.
A case of pelvic inflammatory disease in a sexually non-active 13 year old girl is described, with evidence of pinworms as the cause. Albendazole treatment cleared the infestation but the patient suffered subsequent bouts of lower abdominal pain. The literature is reviewed regarding abdominal pathology associated with ectopic migration of pinworms.
Adolescent↗
The meningococcus tamed?
Serogroup B Neisseria meningitidis is a frequent cause of invasive meningococcal disease, yet there are no effective vaccines suitable for routine immunisation. Limited efficacy has been shown with meningococcal outer membrane vacccines in children 4 years and older. Here we review the status of current research and consider new approaches to development of meningococcal serogroup B vaccines.
Bacterial Outer Membrane Proteins↗
Increased resting bronchial tone in normal subjects acclimatised to altitude.
BACKGROUND: Normal subjects frequently experience troublesome respiratory symptoms when acclimatised to altitude. Bronchial hyperresponsiveness (BHR) and full and partial flow-volume loops were measured before and after ascent to 5000 m altitude to determine if there are changes in resting bronchial tone and BHR that might explain the symptoms. METHODS: BHR to histamine was measured using a turbine spirometer to record partial and full flow-volume curves and expressed as log dose slopes. Twenty one subjects were tested at sea level and after acclimatisation at 5000 m altitude. RESULTS: No significant change in log dose slope measurements of forced expiratory volume in 1 second occurred after acclimatisation, and the maximal expiratory flow with 30% of forced vital capacity remaining (MEF(30%)) rose on the full loop and fell on the partial loop. Their ratio (full divided by partial) rose on average by 0.28 (95% confidence limits 0.14 to 0.42) from the mean (SD) sea level value of 0.87 (0.20). CONCLUSIONS: There is no increase in BHR in normal subjects acclimatised to altitude but an increase in resting bronchial tone occurs that could be released by deep inspiration. This may be the result of increased cholinergic tone.
Adaptation, Physiological↗
Vaccine prevention of meningococcal disease, coming soon?
The past century has seen the use of a number of vaccines for prevention and control of meningococcal disease with varied success. The use of polysaccharide vaccines for the control of outbreaks of serogroup C infections in teenagers and young adults and epidemic serogroup A disease has been established for 30 years and an effective protein-polysaccharide conjugate vaccine against serogroup C was introduced into the UK infant immunisation schedule in 2000. The next generation of these glycoconjugate vaccines will be on the shelf soon, eventually offering the prospect of eradication of serogroups A, C, Y and W135 through routine infant immunisation. Despite these exciting prospects, serogroup B meningococci still account for a majority of infections in industrialised nations but development of safe, immunogenic and effective serogroup B meningococcal vaccines has been an elusive goal. Outer membrane vesicle vaccines for B disease are already used in some countries, and will likely be used more widely in the next few years, but efficacy for endemic disease in children has so far been disappointing. However, the innovations arising from the availability of the meningococcal genome sequence, public and scientific interest in the disease and recent pharmaceutical company investment in development of serogroup B vaccines may have started the countdown to the end of meningococcal infection in children.
Antigens, Bacterial↗
Two distinct receptors mediate nonopsonic phagocytosis of different strains of Pseudomonas aeruginosa.
Complement receptor 3 (CR3) mediates both opsonic and nonopsonic phagocytosis of bacteria. Leukocyte adhesion deficiency (LAD) allows for the study of CR3-dependent phagocyte-bacterial ingestion, since LAD phagocytes do not express this receptor. Phagocytes from an infant with LAD were unable to ingest 50% of the Pseudomonas aeruginosa strains studied, which indicates a requirement for CR3. However, the remaining strains were phagocytosed in the absence of CR3, and ingestion was blocked by monoclonal antibodies directed at CD14. This CR3/CD14 receptor bias was further confirmed by using thioglycollate-elicited murine peritoneal macrophages, which have nonfunctional CR3 before activation. Results indicate that either CR3 or CD14 is involved independently in nonopsonic phagocytosis of different P. aeruginosa strains. Clearance of P. aeruginosa from the endobronchial space may be facilitated by nonopsonic phagocytosis, since low levels of opsonins are present. The impact of lung infection with P. aeruginosa may be determined, in part, by the phagocytic receptor that mediates ingestion.
Adult↗