Impact of meningococcal ACWY conjugate vaccines on pharyngeal carriage in adolescents: evidence for herd protection from the UK MenACWY programme.

OBJECTIVE: Serogroup W and Y invasive meningococcal disease increased globally from 2000 onwards. Responding to a rapid increase in serogroup W clonal complex 11 (W:cc11) invasive meningococcal disease, the UK replaced an adolescent booster dose of meningococcal C conjugate vaccine with quadrivalent MenACWY conjugate vaccine in 2015. By 2018, the vaccine coverage in the eligible school cohorts aged 14 to 19 years was 84%. We assessed the impact of the MenACWY vaccination programme on meningococcal carriage. METHODS: An observational study of culture-defined oropharyngeal meningococcal carriage prevalence before and after the start of the MenACWY vaccination programme in UK school students, aged 15 to 19 years, using two cross-sectional studies: 2014 to 2015 "UKMenCar4" and 2018 "Be on the TEAM" (ISRCTN75858406). RESULTS: A total of 10 625 participants preimplementation and 13 438 postimplementation were included. Carriage of genogroups C, W, and Y (combined) decreased from 2.03 to 0.71% (OR 0.34 [95% CI 0.27-0.44], p < 0.001). Carriage of genogroup B meningococci did not change (1.26% vs 1.23% [95% CI 0.77-1.22], p = 0.80) and genogroup C remained rare (n = 7/10 625 vs 17/13 438, p = 0.135). The proportion of serogroup positive isolates (i.e. those expressing capsule) decreased for genogroup W by 53.8% (95% CI -5.0 - 79.8, p = 0.016) and for genogroup Y by 30.1% (95% CI 8.946·3, p = 0.0025). DISCUSSION: The UK MenACWY vaccination programme reduced carriage acquisition of genogroup and serogroup Y and W meningococci and sustained low levels of genogroup C carriage. These data support the use of quadrivalent MenACWY conjugate vaccine for indirect (herd) protection.

Meningococcal carriage in periods of high and low invasive meningococcal disease incidence in the UK: comparison of UKMenCar1-4 cross-sectional survey results.

BACKGROUND: The incidence of invasive meningococcal disease in the UK decreased by approximately four times from 1999 to 2014, with reductions in serogroup C and serogroup B disease. Lower serogroup C invasive meningococcal disease incidence was attributable to implementation of the meningococcal serogroup C conjugate vaccine in 1999, through direct and indirect protection, but no vaccine was implemented against serogroup B disease. UK Meningococcal Carriage surveys 1-3 (UKMenCar1-3), conducted in 1999, 2000, and 2001, were essential for understanding the impact of vaccination. To investigate the decline in invasive meningococcal disease incidence, we did a large oropharyngeal carriage survey in 2014-15, immediately before the changes to meningococcal vaccines in the UK national immunisation schedule. METHODS: UKMenCar4 was a cross-sectional survey in adolescents aged 15-19 years who were enrolled from schools and colleges geographically local to one of 11 UK sampling centres between Sept 1, 2014, and March 30, 2015. Participants provided an oropharyngeal swab sample and completed a questionnaire on risk factors for carriage, including social behaviours. Samples were cultured for putative Neisseria spp, which were characterised with serogrouping and whole-genome sequencing. Data from this study were compared with the results from the UKMenCar1-3 surveys (1999-2001). FINDINGS: From the 19 641 participants (11 332 female, 8242 male, 67 not stated) in UKMenCar4 with culturable swabs and completed risk-factor questionnaires, 1420 meningococci were isolated, with a carriage prevalence of 7·23% (95% CI 6·88-7·60). Carriage prevalence was substantially lower in UKMenCar4 than in the previous surveys: carriage prevalence was 16·6% (95% CI 15·89-17·22; 2306/13 901) in UKMenCar1 (1999), 17·6% (17·05-18·22; 2873/16 295) in UKMenCar2 (2000), and 18·7% (18·12-19·27; 3283/17 569) in UKMenCar3 (2001). Carriage prevalence was lower for all serogroups in UKMenCar4 than in UKMenCar1-3, except for serogroup Y, which was unchanged. The prevalence of carriage-promoting social behaviours decreased from 1999 to 2014-15, with individuals reporting regular cigarette smoking decreasing from 2932 (21·5%) of 13 650 to 2202 (11·2%) of 19 641, kissing in the past week from 6127 (44·8%) of 13 679 to 7320 (37·3%) of 19 641, and attendance at pubs and nightclubs in the past week from 8436 (62·1%) of 13 594 to 7662 (39·0%) of 19 641 (all p<0·0001). INTERPRETATION: We show that meningococcal carriage prevalence in adolescents sampled nationally during a low incidence period (2014-15) was less than half of that in an equivalent population during a high incidence period (1999-2001). Disease and carriage caused by serogroup C was well controlled by ongoing vaccination. The prevalence of behaviours associated with carriage declined, suggesting that public health policies aimed at influencing behaviour might have further reduced disease. FUNDING: Wellcome Trust, UK Department of Health, and National Institute for Health Research.

Assessing the population impact of low rates of vitamin D supplementation on type 1 diabetes using a new statistical method.

Vitamin D supplementation for all children <5 is recommended by the UK Department of Health for its skeletal effects. Vitamin D is also linked with a number of extra-skeletal effects; one of them being protection against type 1 diabetes. With a rapid increase in the incidence of type 1 diabetes and the associated costs, measures of curtailing the rapid increase of type 1 diabetes are needed. In this review, we look at type 1 diabetes using a statistical method (PIN-ER-t) and published data in an attempt to quantify the impact on the population of babies born in 2012 of increasing vitamin D supplementation rates. Calculations show that for the population of 729,674 babies born in England and Wales in 2012, 374 cases of type 1 diabetes (out of 1357 total predicted) could be prevented over 18 years if all were supplemented with vitamin D. This could lead to savings in excess of £62 million for the cohort. This piece of work adds to the argument for studying the potential link between vitamin D supplementation and type 1 diabetes further.

Cooling in surgical patients: two case reports.

Moderate induced hypothermia has become standard of care for children with peripartum hypoxic ischaemic encephalopathy. However, children with congenital abnormalities and conditions requiring surgical intervention have been excluded from randomised controlled trials investigating this, in view of concerns regarding the potential side effects of cooling that can affect surgery. We report two cases of children, born with congenital conditions requiring surgery, who were successfully cooled and stabilised medically before undergoing surgery. Our first patient was diagnosed after birth with duodenal atresia after prolonged resuscitation, while the second had an antenatal diagnosis of left-sided congenital diaphragmatic hernia and suffered an episode of hypoxia at birth. They both met the criteria for cooling and after weighing the pros and cons, this was initiated. Both patients were medically stabilised and successfully underwent therapeutic hypothermia. Potential complications were investigated for and treated as required before they both underwent surgery successfully. We review the potential side effects of cooling, especially regarding coagulation defects. We conclude that newborns with conditions requiring surgery need not be excluded from therapeutic hypothermia if they might benefit from it.

Intravenous immunoglobulins for the management of Stevens-Johnson syndrome with minimal skin manifestations.

Here we describe the successful use of intravenous immunoglobulin (IVIG) in the management of mycoplasma-induced, atypical Stevens-Johnson syndrome (SJS) with minimal skin manifestations. The patient was successfully managed with high-dose IVIG 0.5 g/kg for 4 consecutive days. No complications were noted. IVIG may be useful in the management of mycoplasma-induced SJS.

Chest reexploration in the intensive care unit after cardiac surgery: a safe alternative to returning to the operating theater.

BACKGROUND: The aim of this study was to determine the outcome of patients who had chest reexploration in the intensive care unit (ICU) for bleeding or cardiovascular instability after heart surgery. METHODS: This was a retrospective analysis of medical records of patients who had a chest reexploration in the ICU for bleeding or possible cardiac tamponade over a 9-year period (1991 to 2000), at the Cardiothoracic Centre of Manchester Royal Infirmary, England. RESULTS: Between 1991 and 2000, 240 patients (3.4% of the total heart operations) who fitted the above criteria were identified. Two hundred and seven (86%) were reexplored for bleeding, 22 (9%) for possible tamponade, and 11 (5%) for both. Ninety-five percent were reexplored within 24 hours (median, 5 to 6 hours). Two hundred and twenty-six patients were found to have bleeding on reexploration. Of these, 125 (55%) were found to have focal bleeding, 74 (33%) diffuse bleeding, and 11 (5%) both. Two hundred and twelve (88%) had their chest closed, 25 (12%) packed, and 13 (10%) had further chest openings while in ICU. Sixteen (6.7%) of the patients died. Seven (2.9%) had sternal wound infection. For the survivors, ICU stay ranged from 1 to 60 days (median, 1) and their hospital stay ranged from 2 to 90 days (median, 8). CONCLUSIONS: Chest reexploration in ICU for bleeding or tamponade after heart surgery can be a safe alternative to return to the operating theater.

Taurine transport into fetal cord blood cells: inhibition by cyclosporine A.

OBJECTIVES: Pregnant women undergoing long-term organ transplant treatment have an increased incidence of delivering infants with intrauterine growth restriction (IUGR). Cyclosporine A is used as an immunosuppressant in such women and indirect evidence suggests that IUGR might result from an effect of cyclosporine A on amino acid transport by the placenta. In this study we tested the hypothesis that the transport of an essential amino acid, taurine, by fetal tissue other than the placenta is modulated by cyclosporine A. METHODS: Cord blood cells (CBCs) were used to test this hypothesis as an easily obtainable fetal tissue. Transport of taurine into CBCs was measured using standard tracer flux assays. RESULTS: Uptake of [(3)H] taurine by CBCs was linear over 15 minutes (76.2 +/- 16.6 fmol/10(6) cells/min, mean +/- SEM, n = 6) and inhibitable by 10 mM beta-alanine, a substrate of the system-beta taurine transport protein (6.7 +/- 1.0 fmol/10(6) cells/min, n = 6, P <.05, paired Student t test). Pre-incubation with cyclosporine A (5 microM) inhibited [(3)H] taurine uptake by 29.3%-5.3% (n = 8, P <.05, paired Student t test). CONCLUSIONS: These data show that amino acid transport via system-beta can be measured in CBCs and may be a useful model for amino acid transport studies in fetal cells. We also show that system-beta was inhibited by the immunosuppressant, cyclosporine A. This suggests that the increased incidence of IUGR reported in mothers treated with cyclosporine A may be due partially to effects on taurine uptake into fetal cells outside the placenta.

Caring for a child with spina bifida: understanding the child and carer.

Spina bifida is a common congenital abnormality, which causes significant physical and psychological morbidity in affected children and which also affects their carers. This small-scale study looked at the health problems of a child with a myelomeningocoele. It also addresses the psychosocial problems that his mother, his main carer, faced and the social networks involved in his care. The evidence supporting various aspects of spina bifida prevention and management is explored. Furthermore, a literature review is included, with regards to physical and psychological issues for child and carer. This study aims to raise awareness of the problems faced by children with myelomeningocoele and their families. In particular, we aim to educate health care professionals on the importance of perceived stress by carers of such children, and suggest ways to reduce psychosocial morbidity.