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

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

The global meningitis genome partnership

GGenomic surveillance of bacterial meningitis pathogens is essential for effective disease control globally, enabling identification of emerging and expanding strains and consequent public health interventions. While there has been a rise in the use of whole genome sequencing, this has been driven predominately by a subset of countries with adequate capacity and resources. Global capacity to participate in surveillance needs to be expanded, particularly in low and middle-income countries with high disease burdens. In light of this, the WHO-led collaboration, Defeating Meningitis by 2030 Global Roadmap, has called for the establishment of a Global Meningitis Genome Partnership that links resources for: N. meningitidis (Nm), S. pneumoniae (Sp), H. influenzae (Hi) and S. agalactiae (Sa) to improve worldwide co-ordination of strain identification and tracking. Existing platforms containing relevant genomes include: PubMLST: Nm (31,622), Sp (15,132), Hi (1935), Sa (9026); The Wellcome Sanger Institute: Nm (13,711), Sp (> 24,000), Sa (6200), Hi (1738); and BMGAP: Nm (8785), Hi (2030). A steering group is being established to coordinate the initiative and encourage high-quality data curation. Next steps include: developing guidelines on open-access sharing of genomic data; defining a core set of metadata; and facilitating development of user-friendly interfaces that represent publicly available data

The impact of antiretroviral therapy on HPV and cervical intraepithelial neoplasia: current evidence and directions for future research

Increasing numbers of human immunodeficiency virus (HIV)-infected women are now accessing life-prolonging highly active antiretroviral therapy (HAART) in developing countries. There is a need for better understanding of interactions of human papillomavirus (HPV) and HIV, especially in the context of increasing life expectancy due to HAART. The data regarding the impact of HAART on reducing the incidence and progression and facilitating the regression of HPV infection and cervical abnormalities is largely inconsistent. Published studies differ in their study designs (prospective or retrospective cohorts or record linkage studies), screening and diagnostic protocols, duration and type of HAART use, recruitment and referral strategies, and definitions of screening test and disease positivity. Due to the ethical and resource limitations in conducting randomized trials of the impact of HAART on incidence of HPV, CIN, and cervical cancer among HIV-infected women, it is important to consider innovative study designs, including quasi-experimental trials and operations research in sentinel populations to answer the critical research questions in this area

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

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

OBJECTIVES: Serogroup W and Y invasive meningococcal disease (IMD) increased globally from 2000 onwards. Responding to a rapid increase in serogroup W clonal complex 11 (W:cc11) IMD, the UK replaced an adolescent booster dose of meningococcal C conjugate vaccine with quadrivalent MenACWY conjugate vaccine in 2015. By 2018, vaccine coverage in the eligible school cohorts aged 14-19 years-old 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 15-19 years, using two cross-sectional studies: 2014-15 "UKMenCar4" and 2018 "Be on the TEAM" (ISRCTN75858406). RESULTS: A total of 10625 participants pre-implementation and 13434 post-implementation 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 = 7/10625 vs 17/13488, 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 8·9%-46·3%, p=0·0025). CONCLUSIONS: 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

Early diagnosis and treatment of postoperative endoscopic recurrence of Crohn's disease: partial benefit by infiximab - A pilot study

Goals: Primary outcome of this study was to clarify whether infliximab, given after diagnosis of post operative endoscopic recurrence of Crohn\u2019s diseases, can heal mucosal lesions (score &lt;2) at 54 weeks. The secondary outcomes were improvement in the endoscopic score and clinical recurrence at 54 weeks. Background: Current data indicate that infliximab - given immediately after surgery \u2013 may be very effective in preventing postsurgical recurrence of Crohn\u2019s disease. However, it is unknown whether a similar benefit would result from early diagnosis and treatment, rather then prevention, of endoscopic recurrence. Study: In this prospective open label multicenter pilot study 43 patients with ileocolonic Crohn\u2019s disease subjected to curative surgery underwent colonoscopy 6 months after surgery. Patients with endoscopic recurrence (Rutgeerts score 65 2) were treated with either mesalamine 800 mg tid or infliximab 5 mg/Kg bw on a maintenance basis. Colonoscopy was performed after 54 weeks of therapy. Results: A total of 24/43 patients were diagnosed with endoscopic recurrence at 6 months. Thirteen were treated with infliximab and eleven with mesalamine. None of the 11 mesalamine treated patients had mucosal healing at 54 weeks. Two had clinical recurrence at 8 and 9 months. Fifty-four percent of patients treated with infliximab had mucosal healing at 54 weeks (p=0.01) while 69% had an improvement in the endoscopic score. None had clinical recurrence. Conclusions: Treatment of postsurgical endoscopic lesions by infliximab appears superior to mesalamine. However a sizeable proportion of patients did not fully benefit from this strategy