Dataset Information

UKMenCar4: A cross-sectional survey of asymptomatic meningococcal carriage amongst UK adolescents at a period of low invasive meningococcal disease incidence.

ABSTRACT: Carriage of Neisseria meningitidis, the meningococcus, is a prerequisite for invasive meningococcal disease (IMD), a potentially devastating infection that disproportionately afflicts infants and children. Humans are the sole known reservoir for the meningococcus, and it is carried asymptomatically in the nasopharynx of ~10% of the population. Rates of carriage are dependent on age of the host and social and behavioural factors. In the UK, meningococcal carriage has been studied through large, multi-centre carriage surveys of adolescents in 1999, 2000, and 2001, demonstrating carriage can be affected by immunisation with the capsular group C meningococcal conjugate vaccine, inducing population immunity against carriage. Fifteen years after these surveys were carried out, invasive meningococcal disease incidence had declined from a peak in 1999. The UKMenCar4 study was conducted in 2014/15 to investigate rates of carriage amongst the adolescent population during a period of low disease incidence. The protocols and methodology used to perform UKMenCar4, a large carriage survey, are described here.

SUBMITTER: Bratcher HB

PROVIDER: S-EPMC6749934 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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UKMenCar4: A cross-sectional survey of asymptomatic meningococcal carriage amongst UK adolescents at a period of low invasive meningococcal disease incidence.

Bratcher Holly B HB Rodrigues Charlene M C CMC Finn Adam A Wootton Mandy M Cameron J Claire JC Smith Andrew A Heath Paul P Ladhani Shamez S Snape Matthew D MD Pollard Andrew J AJ Cunningham Richard R Borrow Raymond R Trotter Caroline C Gray Stephen J SJ Maiden Martin C J MCJ MacLennan Jenny M JM

Wellcome open research 20191028

Carriage of <i>Neisseria meningitidis</i>, the meningococcus, is a prerequisite for invasive meningococcal disease (IMD), a potentially devastating infection that disproportionately afflicts infants and children. Humans are the sole known reservoir for the meningococcus, and it is carried asymptomatically in the nasopharynx of ~10% of the population. Rates of carriage are dependent on age of the host and social and behavioural factors. In the UK, meningococcal carriage has been studied through l ...[more]

PMID: 31544158

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Project description:BackgroundThe 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.MethodsUKMenCar4 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).FindingsFrom 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).InterpretationWe 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.FundingWellcome Trust, UK Department of Health, and National Institute for Health Research.

Project description:Background: We employed DNA microarray technology to investigate the host response to Streptococcus pneumoniae in a mouse model of asymptomatic carriage. Over a period of six weeks, we profiled transcript abundance and complexity in the Nasal Associated Lymphoid Tissue (NALT) to identify genes whose expression differed between pneumococcal-colonized and uncolonized states. Results: Colonization with S. pneumoniae altered the expression of hundreds of genes over the course of the study, demonstrating that carriage is a dynamic process characterized by increased expression of a set of early inflammatory responses, including induction of a Type 1 Interferon response, and the production of several antimicrobial factors. Subsequent to this initial inflammatory response, we observed increases in transcripts associated with T cell development and activation, as well as wounding, basement membrane remodeling, and cell proliferation. Our analysis suggests that microbial colonization induced expression of genes encoding components critical for controlling JAK/STAT signaling, including stat1, stat2, socs3, and mapk1, as well as induction of several Type 1 Interferon-inducible genes and other antimicrobial factors at the earliest stages of colonization. Conclusions: Examining multiple time points over six weeks of colonization demonstrated that asymptomatic carriage stimulates a dynamic host response characterized by temporal waves with distinct biological programs. Our data suggest that the usual response to the presence of the pneumocccus is an initial controlled inflammatory response followed by activation of host physiological processes such as response to wounding, basement membrane remodeling, and increasing cellular numbers that ultimately allow the host to maintain an intact epithelium and eventually mount a preventive adaptive immune response. A disease state experiment design type is where the state of some disease such as infection, pathology, syndrome, etc is studied.

Project description:Host persistence of bacteria is facilitated by mutational and recombinatorial processes that counteract loss of genetic variation during transmission and selection from evolving host responses. Genetic variation was investigated during persistent asymptomatic carriage of Neisseria meningitidis Interrogation of whole-genome sequences for paired isolates from 25 carriers showed that de novo mutations were infrequent, while horizontal gene transfer occurred in 16% of carriers. Examination of multiple isolates per time point enabled separation of sporadic and transient allelic variation from directional variation. A comprehensive comparative analysis of directional allelic variation with hypermutation of simple sequence repeats and hyperrecombination of class 1 type IV pilus genes detected an average of seven events per carrier and 2:1 bias for changes due to localized hypermutation. Directional genetic variation was focused on the outer membrane with 69% of events occurring in genes encoding enzymatic modifiers of surface structures or outer membrane proteins. Multiple carriers exhibited directional and opposed switching of allelic variants of the surface-located Opa proteins that enables continuous expression of these adhesins alongside antigenic variation. A trend for switching from PilC1 to PilC2 expression was detected, indicating selection for specific alterations in the activities of the type IV pilus, whereas phase variation of restriction modification (RM) systems, as well as associated phasevarions, was infrequent. We conclude that asymptomatic meningococcal carriage on mucosal surfaces is facilitated by frequent localized hypermutation and horizontal gene transfer affecting genes encoding surface modifiers such that optimization of adhesive functions occurs alongside escape of immune responses by antigenic variation.IMPORTANCE Many bacterial pathogens coexist with host organisms, rarely causing disease while adapting to host responses. Neisseria meningitidis, a major cause of meningitis and septicemia, is a frequent persistent colonizer of asymptomatic teenagers/young adults. To assess how genetic variation contributes to host persistence, whole-genome sequencing and hypermutable sequence analyses were performed on multiple isolates obtained from students naturally colonized with meningococci. High frequencies of gene transfer were observed, occurring in 16% of carriers and affecting 51% of all nonhypermutable variable genes. Comparative analyses showed that hypermutable sequences were the major mechanism of variation, causing 2-fold more changes in gene function than other mechanisms. Genetic variation was focused on genes affecting the outer membrane, with directional changes in proteins responsible for bacterial adhesion to host surfaces. This comprehensive examination of genetic plasticity in individual hosts provides a significant new platform for rationale design of approaches to prevent the spread of this pathogen.

Project description:BackgroundUltrasound in podiatry practice encompasses musculoskeletal ultrasound imaging, vascular hand-held Doppler ultrasound and therapeutic ultrasound. Sonography practice is not regulated by the Health and Care Professions Council (HCPC), with no requirement to hold a formal qualification. The College of Podiatry does not currently define ultrasound training and competencies.This study aimed to determine the current use of ultrasound, training received and mentorship received and/or provided by podiatrists using ultrasound.MethodsA quantitative study utilising a cross-sectional, on-line, single-event survey was undertaken within the UK.ResultsCompleted surveys were received from 284 podiatrists; 173 (70%) use ultrasound as part of their general practice, 139 (49%) for musculoskeletal problems, 131 (46%) for vascular assessment and 39 (14%) to support their surgical practice. Almost a quarter (n = 62) worked for more than one organisation; 202 (71%) were employed by the NHS and/or private sector (n = 118, 41%).Nearly all (93%) respondents report using a hand-held vascular Doppler in their daily practice; 216 (82%) to support decisions regarding treatment options, 102 (39%) to provide diagnostic reports for other health professionals, and 34 (13%) to guide nerve blocks.Ultrasound imaging was used by 104 (37%) respondents primarily to aid clinical decision making (n = 81) and guide interventions (steroid injections n = 67; nerve blocks n = 39). Ninety-three percent stated they use ultrasound imaging to treat their own patients, while others scan at the request of other podiatrists (n = 28) or health professionals (n = 18). Few use ultrasound imaging for research (n = 7) or education (n = 2).Only 32 (11%) respondents (n = 20 private sector) use therapeutic ultrasound to treat patients presenting with musculoskeletal complaints, namely tendon pathologies.Few respondents (18%) had completed formal post-graduate CASE (Consortium for the Accreditation of Sonographic Education) accredited ultrasound courses.Forty (14%) respondents receive ultrasound mentorship; the majority from fellow podiatrists (n = 17) or medical colleagues (n = 15). Over half (n = 127) who do not have ultrasound mentorship indicated they would like a mentor predominantly for ultrasound imaging. Fifty-five (19%) report they currently provide ultrasound mentorship for others.ConclusionsUnderstanding the scope of ultrasound practice, the training undertaken and the requirements for mentorship will underpin the development of competencies and recommendations defined by the College of Podiatry to support professional development and ensure safe practice.

Dataset Information

UKMenCar4: A cross-sectional survey of asymptomatic meningococcal carriage amongst UK adolescents at a period of low invasive meningococcal disease incidence.

Publications

UKMenCar4: A cross-sectional survey of asymptomatic meningococcal carriage amongst UK adolescents at a period of low invasive meningococcal disease incidence.

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