[Show abstract][Hide abstract] ABSTRACT: Infants within neonatal intensive care units can receive multiple medically essential painful procedures a day. How they respond to these stimuli, how best to alleviate the negative effects, and the long-term consequences for the infant are all significant questions that have yet to be fully answered. In recent years several studies have examined cortical responses to noxious stimuli in the neonate through the use of near-infrared spectroscopy (NIRS) and electroencephalography (EEG). These investigations dispel any notion that the newborn infant does not process noxious stimuli at a cortical level and open the way for future research. In this Viewpoint article we review these studies and discuss key clinical challenges which may be elucidated with the use of these techniques. Conclusion: Simultaneously measuring the changes that are evoked in behaviour, physiology and the cortex following noxious events will provide the best approach to understanding the neonate's experience of pain. This article is protected by copyright. All rights reserved.
[Show abstract][Hide abstract] ABSTRACT: Background:Concern about the risk of leukaemia in children living near nuclear power plants (NPPs) persists. Previous British analyses have been area based and consequently thought to be less effective than case-control studies.Methods:Cases of childhood leukaemia and non-Hodgkin lymphoma (LNHL) born and diagnosed in Great Britain between 1962 and 2007, with matched cancer-free controls, were analysed by logistic regression to estimate the risk of residential proximity at birth and diagnosis to the nearest NPP, adjusting for relevant variables.Results:For 9821 children with LNHL under the age of 5 years, the estimated extra risk associated with residential proximity to an NPP at birth was negative-interpolated Odds Ratio (OR) at 5 km was 0.86 (0.49-1.52). The comparison of 10 618 children with LNHL under five with 16 760 similarly aged children with other cancers also gave a negative estimate of the extra risk of residential proximity at diagnosis-interpolated OR at 5 km was 0.86 (0.62-1.18).Conclusion:Our results show little evidence of an increase in risk of LNHL to children aged under 5 years from living in the vicinity of an NPP. Risk estimates are incompatible with comparable ones published in a recent German case-control study.British Journal of Cancer advance online publication, 12 September 2013; doi:10.1038/bjc.2013.560 www.bjcancer.com.
[Show abstract][Hide abstract] ABSTRACT: The first meningococcal vaccine with the potential to provide broad coverage against serogroup B disease has recently been approved for use in Europe. This vaccine, multi-component serogroup B vaccine (4CMenB), contains recombinant proteins and outer membrane vesicles, and has been extensively studied in clinical trials involving over 7500 adults, children and infants. As well as demonstrating immunogenicity against a range of serogroup B meningococcal strains, these trials have also demonstrated relatively high rates of fever following infant immunization. This article will summarize the vaccine composition, clinical trials and suggested schedules of this vaccine, with specific attention to immunogenicity, reactogenicity, safety, potential coverage and optimal implementation of this vaccine.
[Show abstract][Hide abstract] ABSTRACT: HLA-B*57 is strongly associated with immune control of HIV and delayed AIDS progression. The closely-related, but less protective, HLA-B*58:01 presents similar epitopes, but HLA-B*58:01(+) individuals do not generate CD8(+) T-cells targeting the KF11-Gag epitope linked with low viraemia. Here we show that HLA-B*58:01 binds and presents KF11 peptide, but HIV infected HLA-B*58:01(+) cells fail to process KF11. This unexpected finding demonstrates that immunodominance patterns can be influenced by intracellular events independent of HLA binding motifs.
[Show abstract][Hide abstract] ABSTRACT: The Vi capsular polysaccharide (ViPS) protects Salmonella enterica subspecies enterica serotype Typhi (S.Typhi) in vivo by multiple mechanisms. Recent microbiological reports from typhoid endemic countries suggest that acapsulate S.Typhi may occur in nature and contribute to clinical typhoid fever that is indistinguishable from disease caused by capsulate strains. The prevalence and genetic basis of ViPS-negative S.Typhi isolates in children from Kathmandu, Nepal, were tested in 68 isolates. Although 5.9% of isolates tested negative for capsular expression by slide agglutination tests, a novel multiplex PCR assay and individual PCR analyses demonstrated the presence of all 14 genes responsible for the synthesis, transportation and regulation of the ViPS. These data suggest that phenotypically acapsulate S.Typhi may not have a genetic basis for the same.
[Show abstract][Hide abstract] ABSTRACT: A quadrivalent meningococcal vaccine conjugated to CRM197 (MenACWY-CRM197) is immunogenic in young infants. We assessed the memory B-cell and antibody responses after a primary and booster course of MenACWY-CRM197 in children. At 5 months of age, following primary immunisation, serogroup-specific memory B-cells were detectable in fewer than 25% of children, although protective antibody titres (hSBA≥4) were detectable in 69% of children against serogroup A and more than 95% against the other serogroups. At 12 months, before booster immunisation the percentages with hSBA≥4 were 5% for serogroup A, and between 44 and 70% for the other serogroups. One month after booster immunisation with MenACWY-CRM197 over 50% of children had detectable memory B-cells, and 91% had hSBA≥4 against serogroup A and more than 99% against the other serogroups. These data show that few antigen-specific anticapsular memory B-cells can be detected after two-doses priming with MenACWY-CRM197. For MenC and CRM197, the antigens with the highest number of B-cells at 5 months, there was a definite (p≤0.02) but weak correlation with antibody persistence at 12 months. Although previous studies suggest that measuring memory B-cell responses after priming immunisations in infancy can be used to predict antibody persistence and memory responses, this may not be suitable for all antigens in young children.
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND AND AIMS:: Maternal-antibodies give neonates some protection against bacterial infection. We measured antibodies against N. meningitidis serogroups A, C, Y and W135 in mothers and their 2 month-old infants at study enrolment. We also assessed the impact of maternal antibody present at 2 months of age on the response to a primary course of quadrivalent meningococcal conjugate vaccine (MenACWY-CRM197) given at 2 and 4 months of age. METHODS:: This was a single centre, open label, randomized study, undertaken in Oxford, United Kingdom. 216 healthy infants were enrolled in the study and vaccinated with MenACWY-CRM197 at 2 and 4 months of age. Blood was obtained from all mothers, and in a subset of infants at 2 months, and all infants at 5 months. Antibody and memory B-cell responses at 5 months were correlated with maternal-antibodies. RESULTS:: Mothers had low IgG antibodies against serogroups C, W135 and Y polysaccharides, but high serogroup A antibody, whereas 61-78% had protective hSBA (≥ 1:4) for serogroups C, W135 and Y but only 31% for serogroup A. Only 9%, 32%, 45% and 19% of 2-month-olds infants had hSBA ≥ 1:4 for serogroups A, C, W135 and Y respectively. Maternal-antibody had little association on responses to MenACWY-CRM197 except a moderate negative association between MenC-specific-bactericidal antibody at 2 months and 5 months (r=-0.5, p=0.006, n=28) and between carrier-specific-IgG-antibody at 2 months and MenC-specific hSBA/IgG-antibody at 5 months (r=-0.4, p= 0.02 and 0.04, n=32 and 23). Nonetheless, 90% of infants achieved protective MenC-hSBA titers after vaccination at 2 and 4 months of age. CONCLUSIONS:: The levels of serogroups specific-meningococcal antibodies were low in mothers and 2 months old infants. Immunizing mothers before or during pregnancy with meningococcal conjugate vaccines might increase antibody levels in early infancy and provide protection against infection due to N. meningitidis.
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVE: To assess persistence of immunity to hepatitis B (HBV) in primary school children vaccinated following perinatal exposure. DESIGN: Serological survey. SETTING: Five UK sites (Berkshire East, Birmingham, Buckinghamshire, Milton Keynes and Oxfordshire). PARTICIPANTS: Children from 3 years 4 months to 10 years of age (mean age 6.2 years), vaccinated against HBV from birth following perinatal exposure. INTERVENTIONS: A single booster dose of the paediatric formulation of a recombinant HBV vaccine. MAIN OUTCOME MEASURES: Titres of antibody against hepatitis B Surface Antigen (anti-HBs) measured immediately before and 21-35 days after the HBV vaccine booster. RESULTS: Prebooster anti-HBs titres were >10 mIU/ml in 84.6% of children (n=26; 95% CI 65.1 to 95.6%). All children (n=25, 95% CI 86.3 to 100%) had titres >100 mIU/ml after the booster. CONCLUSIONS: This study of antibody persistence among UK children born to hepatitis B infected women, immunised with a 3-dose infant schedule with a toddler booster suggests sustained immunity through early childhood. These data should prompt further studies to address the need for a preschool booster. TRIAL REGISTRATION: Eudract Number 2008-004785-98.
Archives of Disease in Childhood 03/2013;
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