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Meningitis & Septicaemia in Children & Adults 2015

Royal Society of Medicine, London, UK Organised by Meningitis Research Foundation 12 CPD Credits (event 99659)

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NOVEMBER

2015

Our offices Bristol Tel 01454 281811 [email protected]

Belfast Tel 028 9032 1283 [email protected]

Dublin Edinburgh Tel 01 819 6931 Tel 0131 510 2345 [email protected] [email protected]

Blantyre, Malawi

A charity registered in England and Wales no 1091105, in Scotland no SC037586 and in Ireland 20034368

Major sponsors:

Sponsor:

Registered Office: Midland Way Thornbury Bristol BS35 2BS © Meningitis Research Foundation 11/2015

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Photograph credit: In the Sports Hall – Guillietta Verdon-Roe

Legacy Novartis Vaccines (non-influenza) is now a GSK company

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Contents Meningitis Research Foundation Conference Meningitis & Septicaemia in Children & Adults 2015 Welcome

page 3

Useful Information

page 4

Steering Committee

page 5

Programme

page 6

Day one morning sessions – abstracts

page 9

Day one afternoon sessions – abstracts

page 12

GSK satellite session

page 14

Day two morning sessions – abstracts

page 16

Day two afternoon sessions – abstracts

page 20

Chair & Speaker Biographies

page 25

Poster Presentations

page 35

Sponsors & Exhibitors

page 76

Introducing Meningitis Research Foundation Meningitis Research Foundation has been at the forefront of the fight against meningitis and septicaemia for over 25 years. A registered charity, we have offices and staff in England, Malawi, Northern Ireland, Ireland and Scotland and links to medical and scientific professionals across the world. Our vision is of a world free from meningitis and septicaemia. We have invested over £18.6 million in vital research to improve prevention, diagnosis and treatment of meningitis and septicaemia.

We also spend £1m a year supporting people affected by the diseases, raising public awareness, and providing professionally endorsed educational resources and algorithms for health professionals. We are building on our track record of significant support for research within and beyond the UK and Ireland while developing new models to tackle the diseases globally, like our Action Meningitis health intervention project in Malawi.

Front cover: MRF Member Discovery Day visit to Imperial College London; Young Members enjoying MRF’s Pushing the Boundaries: Life Beyond Limb Loss day: Discovery Day at PHE Manchester; A baby receives a MenB vaccine in the UK. Back cover: A Health Surveillance Assistant triages as part of MRF’s Action Meningitis health intervention project in Malawi.

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Meningitis & Septicaemia in Children & Adults 2015

Dear delegate, I am delighted to welcome you to Meningitis Research Foundation’s 2015 conference – Meningitis and Septicaemia in Children and Adults - our tenth conference in this series. This year’s event takes place towards the end of a remarkable year of progress in the fight against meningitis and septicaemia. A new vaccine against serogroup B meningococcal disease was included in the UK infant immunisation schedule from September 2015. This followed a long period of discussion about the vaccine’s cost-effectiveness and vigorous campaigning by MRF, supported by thousands of its members affected by the disease, on behalf of children and families at risk. In addition, a vaccine covering meningococcal serogroups A, C, W and Y was introduced into the UK national schedule for teenagers from August 2015. An urgent public health need was established following the rise of a virulent strain of MenW, and this strain was identified using the MRF Meningococcal Genome Library, the first of its kind in the world. I would like to thank our eminent Steering Committee for putting together such a high-quality programme. Over the two days we will be examining clinical management from the perspective of various disciplines, and looking at current successes in vaccination and possibilities for the future. I hope these two days will provide an opportunity for sharing state-of-the-art knowledge on topics of global interest, and for forging new collaborations. It is my great pleasure to welcome our expert speakers from the UK and overseas. In addition to the invited programme of talks we have had an excellent response to our call for posters, with 58 submissions this year. Don’t miss the award for the best poster on Day Two, accompanied by presentations of the top five short-listed ones. At the charity we are working hard towards our vision of a world free from meningitis and septicaemia through research and education, as well as offering support to people affected. We are the only meningitis charity with this active international focus, and the conference includes updates about work in Africa, especially the Meningitis Belt.

Meningitis Research Foundation was set up 26 years ago by a group of parents whose children had been affected by meningitis. Since then we have awarded 147 research grants at a cost of over £18m, mostly funded by public donation. Much of this funding continues to come from families and communities affected by these diseases, and I would like to pay tribute to them for turning their personal tragedies into a powerful force for change. This year the opening session of the conference includes remarks by one of our leading Ambassadors, the Paralympian wheelchair rugby player Aaron Phipps. I am grateful to our sponsors who have supported the event. They are represented here and I hope you will take the opportunity to visit their stands and talk to them. On the charity’s own stand you will find a variety of resources for health professionals together with public education materials. I would also like to thank the session chairs for their help, and my colleagues for their hard work in organising the event. Finally I thank you, the delegates, for working to prevent and treat these deadly diseases as effectively as possible. I hope you find Meningitis Research Foundation’s 2015 conference both informative and enjoyable. Yours sincerely,

Christopher Head Chief Executive

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Useful Information If you have any queries throughout the Conference, please contact a member of the Meningitis Research Foundation (MRF) team. You can identify them by their red badges. The Conference occupies three main areas in the Royal Society of Medicine (RSM): the Max Rayne Atrium (Atrium), The Cavendish Room (Cavendish) and the Guy Whittle Auditorium (Auditorium).

Bulletin board Messages can be left throughout the conference on a special bulletin board at the MRF stand in the Atrium.

Business services Basic services are supplied by RSM including free faxes and paid-for photocopying. Please inquire at the RSM reception on the ground floor. There is also a laptop and printer available for delegate use at the MRF reception desk.

Cloakroom The cloakroom is located on the ground floor, next to the main RSM reception. It is staffed and coats and bags can be stored free of charge. There are also lockers which take £1 coins – refunded when emptied.

Conference evaluations You will find a conference evaluation form in your delegate bag. Please fill in and leave at the MRF reception desk before you leave.

CPD certification The Royal College of Physicians has approved 12 CPD credits (99659) – six per day. You should have enlisted for your CPD certificate at registration. Please make sure your details have been submitted so we can make your certificate available for collection from the MRF registration desk when you leave.

Disabled access There is removable seating in the Auditorium for wheelchairs and a personal hearing system with an RSM receiver and earpiece. Disabled toilets are located on the ground floor, next to the Atrium.

Exhibitions Our sponsors have stands in the Atrium, together with an MRF stand. You can visit during registration, coffee breaks and lunch on both days and during the Wine Reception on day one.

Fire & evacuation procedure If the fire alarm sounds, it will be followed by a PA announcement about the cause. Should an investigation result in an emergency evacuation, a further PA announcement will be made. Proceed quickly and calmly to the nearest fire exit. Escape routes and emergency exits are clearly indicated by the Fire Exit signs. The assembly point is in Cavendish Square. RSM Fire Wardens will give any instructions needed and these must be followed. Do not stop to collect personal possessions and do not use the lifts. Those needing assistance will be helped by MRF staff.

First Aid RSM has numerous qualified first aiders. If an accident occurs, please alert MRF staff and contact RSM reception on the ground floor.

Internet access Complimentary Wi-Fi access is available throughout RSM. The access password is available from MRF reception and MRF’s stand in the Atrium.

Lunch & refreshments Both lunches and all refreshments are served in the Atrium and Cavendish room.

Mobile phones, landlines & pagers The signal in RSM is strong enough for most providers but please put all mobile phones in silent mode when you are in the Auditorium. Mobile phones can be used outside the Auditorium. RSM will not take messages for delegates via its switchboard but there is a public, coin operated telephone in the cloakroom on the ground floor should you need a landline.

Parking There is no parking at RSM and limited meter parking in the neighbouring streets but there are numerous car parks in the area, including one directly under Cavendish Square.

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Meningitis & Septicaemia in Children & Adults 2015

Photography

Conference 2015 Steering Committee

MRF staff and a professional photographer will be taking photographs discreetly at some points during the conference. These photographs may be used in multimedia formats to promote future MRF activity. If you do not want to be photographed or have your image used in this manner, please make yourself known to MRF staff.

Prof Ian Feavers, National Institute for Biological Standards and Control

Posters

Prof Adam Finn, University of Bristol

Over 50 posters have been submitted and these are displayed in Cavendish. You can visit them during registration, coffee breaks and lunch on both days and during the Wine Reception on day one.

Prof Sir Brian Greenwood, London School of Hygiene and Tropical Medicine

Questions during the conference

Prof Paul Heath, St George’s University of London

Questions will be taken at the discretion of each Chair. Please wait until questions are invited and raise your hand and when you are called please give your name and where you are from. Each delegate seat has a microphone handset. To use the microphone handset hold it as you would a mobile phone. Press the blue button continuously while you are speaking. Remember to release the button when you have finished speaking or the speaker’s microphone won’t work.

Prof Robert Heyderman, University College London

Smoking

Dr Mary Ramsay, Public Health England, London

RSM is a no smoking building. It is not permitted in any part of the building or on the pavements outside.

Prof Christoph Tang, University of Oxford

Toilets These are located downstairs, through the Atrium, by the Auditorium. Disabled facilities are available on the ground floor, next to the Atrium.

Voting Should any of the presentations require delegate participation, a voting button is built into the microphone handset in the Auditorium seating.

Wine Reception

Prof Ray Borrow, Public Health England, Vaccine Evaluation Unit, Manchester

Prof George Griffin, St George’s University of London

Prof Nigel Klein, Great Ormond Street Children’s Hospital and Institute of Child Health, University College London Prof David Lalloo, Liverpool School of Tropical Medicine Dr Simon Nadel, St Mary’s Hospital, Imperial College London

Dr Caroline Trotter, University of Cambridge Linda Glennie, Meningitis Research Foundation

Major sponsors: GSK; Novartis Vaccines - Legacy Novartis Vaccines (non-influenza) is now a GSK company

Sponsor and supporter: Pfizer

Everyone is invited to this reception which follows the final presentation on day one. It’s being held in the Atrium and the Cavendish room. Legacy Novartis Vaccines (non-influenza) is now a GSK company

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Programme – Wednesday 4 November 2015 8:00 REGISTRATION & COFFEE 9:10 Welcome  Chris Head, CEO, Meningitis Research Foundation (MRF)

9:20 Patient experience of meningococcal disease Aaron Phipps, London 2012 Paralympic Wheelchair

Rugby athlete and MRF Ambassador

Current issues in clinical management Chair: Dr Simon Nadel, St Mary’s Hospital/Imperial College, London 9:40  Revision of the Surviving Sepsis Guidelines: an appraisal of the evidence base  Prof Richard Beale, Intensive Care, Guy’s and St Thomas’ Hospital, London

10:10 T  he UK Joint Specialist Societies’ Guideline on Acute Meningitis and Meningococcal Sepsis in Adults Dr Fiona McGill, University of Liverpool 10:40 COFFEE, EXHIBITION AND POSTERS

Group B Streptococcal and neonatal infection Chair:  Prof Robert Heyderman, University College London

11:10  Clinical care of neonatal meningitis in the UK

Dr Ifeanyichukwu Okike, Derby Children’s Hospital

11:40 A  etiology, presentation and outcome of neonatal meningitis and sepsis including GBS in Africa  Dr Queen Dube, Queen Elizabeth Central Hospital, Malawi

12:10 Prospects for prevention of GBS  Dr Imma Margarit Y Ros, GSK, Siena 12:40 LUNCH, EXHIBITION AND POSTERS

Meningococcal carriage and herd protection Chair:  Dr Caroline Trotter, University of

Cambridge

13:40  Meningococcal carriage in the African meningitis belt and the impact of MenAfriVac: an overview of the MenAfriCar project  Prof Sir Brian Greenwood, London School of Hygiene and Tropical Medicine

14:10  The UKMenCar4 study: carriage studies, high-resolution genomics and disease control  Prof Martin Maiden, University of

Oxford

14:40  DEBATE: Adolescent immunisation against meningococcal B disease should be introduced now  Prof Robert Read, University of Southampton vs Prof Adam Finn, University of Bristol 15:20 TEA, EXHIBITION AND POSTERS

Preventing pneumococcal disease Chair:  Prof Adam Finn, University of

Bristol

15:50  Impact of 13V pneumococcal vaccine on invasive pneumococcal disease and meningitis in the UK  Prof. Elizabeth Miller, Public Health England, London

16:20  Prospects for future prevention of pneumococcal infection

Dr Mark Alderson, PATH, Seattle

GSK Satellite Session Pneumococcal vaccination – Is What You See What You Get? Chair:  Dr Norman Begg, GSK Vaccines, Wavre 16:55 10 valent conjugated pneumococcal vaccine – expectations and reality. Dr Christopher Clarke, GSK Vaccines, Wavre 17:25 Emerging non-vaccine types – what is next and should we care? Dr William Hausdorff, GSK Vaccines, Wavre 17:55 EVENING WINE RECEPTION for all delegates and participants

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Programme – Thursday 5 November 2015 8:00

REGISTRATION & BREAKFAST

Controlling meningococcal disease around the globe

12:10 LUNCH, EXHIBITION AND POSTERS

Poster presentations Chair  Prof David Lalloo, Liverpool School of Tropical Medicine

Chair:  Prof Ray Borrow, Public Health England Vaccine Evaluation Unit, Manchester

13:10 C41 Dr Olivier Manigart, London School of Hygiene and Tropical Medicine

Emergence of a virulent new meningococcal W sequence type 11 in South America and the UK

13:16 E26 Helen Campbell, Public Health England, London

 he South American experience, control 9.00 T measures and impact

13:28 V9 Dr Gunnstein Norheim,

 Dr Marco Safadi, Department of

13:34 P57 Hayley Lavender, University of

Pediatrics,

FCM da Santa Casa de Sao Paulo

9.25 F  irst use of genomics to inform national meningococcal immunisation policy Dr Jay Lucidarme, Public Health England Vaccine Evaluation Unit, Manchester

9:50 E  xperience and impact of Bexsero in a regional programme in Quebec  Prof Philippe de Wals, Laval University, Quebec City

10.20 COFFEE, EXHIBITION AND POSTERS

Controlling meningococcal disease around the globe Chair:  Prof Sir Brian Greenwood, London School of Hygiene and Tropical Medicine

10:50  The impact of MenAfriVac in the Meningitis Belt and prospects for meningococcal disease prevention through EPI and higher valent vaccines  Dr Marie-Pierre Preziosi, Initiative for Vaccine Research, Department of Immunization, Vaccines and Biologicals, World Health Organization, Geneva

13:22 PH51 Eisin McDonald, Health Protection Scotland Norwegian Institute of Public Health Oxford

13:40 Award for the best poster

Advances from research Prof Nigel Klein, University of London Chair:  13:50  Host genetic control of susceptibility and outcome of meningococcal disease Prof Michael Levin, Imperial College London/St Mary’s 14:15  Meningococcemia, a disease of the endothelial cells Prof Xavier Nassif, INSERM, Paris 14:40  Epidemics of Non-typhoidal Salmonella Sepsis and Meningitis in Africa Prof Robert Heyderman, University College, London 15:05 COFFEE, EXHIBITION AND POSTERS

Prevention of meningococcal disease in the UK Prof Ian Feavers, National Institute for Biological Chair:  Standards and Control

15:30  Introduction of Bexsero and MenACWY in the UK Dr Mary Ramsay, Public Health England, London

11:15  Current epidemiology of meningococcal disease in the Meningitis Belt and new WHO outbreak response guidelines after the Meningitis Vaccine Project

16:10  Plans for enhanced surveillance and evaluation of efficacy of Bexsero Prof Ray Borrow, Public Health England Vaccine

 Dr Olivier Ronveaux,

16:40  Implementation and evaluation of new vaccination programmes in the UK Panel discussion Q&A Dr Mary Ramsay; Prof Ray Borrow; Dr Caroline Trotter; Dr Matthew Snape, University of Oxford; Dr Shamez Ladhani, Public Health England, London; Dr Helen Bedford, University College, London

World Health Organization, Geneva

11:40  Impact of the introduction of 4CMenB vaccine on immunity during a MenB outbreak at a university in the US: Epidemiology, Vaccine Uptake and Immune Response  Dr Nicole Basta, University of

Minnesota, School of Public Health, Division of Epidemiology

Evaluation Unit, Manchester

17:10 CLOSE

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Oral Presentations

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2015 Captions:  MRF student supporters celebrate on top on Kilimanjaro, Visiting MRF’s Action Meningitis health intervention project in Malawi A baby receives a MenB vaccine in the UK

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Morning – Wednesday 4 November 2015 9:10 Welcome  hris Head, CEO, C Meningitis Research Foundation

9:20 Patient experience of meningococcal disease  Aaron Phipps, London 2012 Paralympic Wheelchair Rugby athlete and MRF Ambassador

Aaron took a keen interest in extreme sports as a teenager such as rollerblading, skateboarding and BMX riding, as well as playing basketball for his school team. At 15 years of age he contracted meningococcal septicaemia. This presented as seemingly harmless flu-like symptoms, which 12 hours later saw him on a life support machine.  Aaron’s life had turned upside down and after being in a controlled coma for two weeks, both his legs and most of his fingers had to be amputated. Although Aaron had to stay in hospital for a year recovering and rehabilitating, he adapted quickly to the life changing situation thrown at him. Eight months after being discharged, he enrolled at college in an attempt to gain A-level qualifications as his life returned to some kind of normality. Since then he has returned to his love of sports and taken up wheelchair racing which saw him finishing as the fourth highest placed UK male in the 2009 London Marathon. He was selected to represent Team GB at the London 2012 Paralympic Games as a member of the GB wheelchair rugby squad.   Aaron is happily married to Vicky and has two little girls, Ella and Chloe. Aaron is currently training to climb Mount Kilimanjaro. 

Current issues in clinical management Chair: Dr Simon Nadel, St Mary’s Hospital/Imperial College, London 9:40  Revision of the Surviving Sepsis Guidelines: an appraisal of the evidence base  Prof Richard Beale, Intensive Care, Guy’s and St Thomas’ Hospital, London

10:10 T  he UK Joint Specialist Societies Guideline on Acute Meningitis and Meningococcal Sepsis in Adults  Dr Fiona McGill, University of Liverpool Bacterial meningitis and meningococcal sepsis are relatively rare conditions in the UK with high case fatality rates. Early recognition and prompt treatment saves lives. In 1999 the British Infection Society (predecessor of the British Infection Association) produced a consensus statement to guide the management of immunocompetent adult patients with

meningitis and meningococcal sepsis. Additionally, an algorithm and poster were produced in 2003. Since then the epidemiology has changed and there have been new developments in diagnostic methods and treatments. A proposal was made to the BIA that the 1999 consensus statement should be revised and updated. These 2015 guidelines aim to provide a standardised evidence-based approach to the management of acute community acquired meningitis, including viral meningitis, and meningococcal sepsis in adults. A working party representing key national professional associations and consisting of infectious diseases physicians, neurologists, an acute physician, intensivists, microbiologists, public health experts and patient group representatives was formed. Key questions were identified and agreed on by the whole working party. The literature that has arisen since 1999 was then systematically reviewed and critically appraised in order to revise the recommendations accordingly. All recommendations were graded and agreed upon by the working party. The guidelines were written in accordance with the AGREE 2 tool and recommendations graded according to the GRADE system. In addition to the main guideline both an updated version of the one page algorithm was produced as well as an audit tool to assist in implementation of the guideline. The main changes from the previous guidelines will be discussed and include the indications for pre-hospital antibiotics, timing of the lumbar puncture and the indications for neuroimaging. The list of relevant investigations has been updated to include the use of such things as procalcitonin and CSF lactate; more emphasis is placed on molecular methods of diagnosis. Approaches to both antibiotic and steroid therapy have also been revised, including a pragmatic recommendation on how long after antibiotics steroids can be given; the evidence for other adjunctive therapies is also reviewed. Several recommendations have been given regarding the follow-up of patients and, for the first time, the investigation and management of viral meningitis are also considered. A number of studies have shown that there are frequently inappropriate investigations and delays in appropriate treatment when it comes to managing patients with meningitis. Recent publications from other countries have suggested that new, up to date guidance can have a beneficial effect on mortality at a population level. It is our hope that these guidelines, which will be officially launched at the end of 2015, will have a similar impact in the UK. 10:40 COFFEE, EXHIBITION AND POSTERS

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Morning – Wednesday 4 November 2015 Group B Streptococcal and neonatal infection Chair:  Prof Robert Heyderman, University College, London

11:10 Clinical care of neonatal meningitis in the UK Dr Ifeanyichukwu Okike, Derby Children’s Hospital Bacterial meningitis in young infants remains a significant cause of mortality and morbidity. The incidence and case fatality rate in UK neonates is unchanged over the last two decades. The most recent UK population based study showed that non-specific clinical features dominated, and fever was absent in 153 (47%) of cases at presentation. GBS (150, 50%) and Escherichia coli (40, 13%) remain the leading causes. Identified bacteria varied by age and route of admission. There were no cases of listeria meningitis in infants older than 30 days and cefotaxime alone seem to be an appropriate empiric cover for this group. At discharge, 26% had a poor early outcome (death or serious neurological complication). The impact of the existing initiatives (vaccines and guidelines) on the burden and outcome in this age group seems to be limited. Between September 2010 and June 2013, using parental questionnaire, medical notes and expert panel review we assessed in detail the current management in the UK. Of the 97 confirmed cases recruited across England and Wales, 66 (68%) were admitted from home (H) and 31 (32%) were already in hospital (IP) prior to the onset of the meningitis. The median age was14 days (IQR 3-25) and was higher in H cases 17 days (1134) compared to IP cases 1 day (0-7), p=0.0001. The median time from onset of features to first help for H cases was 4.8 hours (IQR: 2-10). Most parents 47/62 (76%) presented to hospital within 24 hours of onset of features at home. 28/66 (42%) were assessed to have encountered inappropriate pre-hospital management. At the time of presentation 40 (61%) had fever and 21 (32%) had seizures whilst 36 (55%) received at least one fluid bolus. The median time from triage to first dose of antibiotics was 2.0 hours (IQR: 1.0-3.3; > 1 hour in 43 (73%)), significantly shorter in infants who had fever or seizures at presentation 1.7 hours (IQR: 1 .0-3.0) compared to those who did not 4.2 hours (IQR: 1.86.3), p=0.02. The empiric antibiotics started on 35/66 (53%) were not in conformity with the NICE bacterial meningitis guideline. Follow up duration was 75% of CSF samples) and in both countries, the strain was identified as ST10217, belonging to an unassigned clonal complex. The epidemic response included the vaccination of 1.5 million people with a multivalent polysaccharide vaccine (ACW and ACYW) and, for the first time in Africa, the vaccination of 200,000 persons with a multivalent conjugate vaccine in Niger.

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Morning – Thursday 5 November 2015 This epidemiological transition triggered the need to review the evidence and recommendations for epidemic control as they were directed mainly at the control of NmA epidemics (Weekly Epidemiological Record 2014; 89:580-6).  nalyses performed on non-A serogroup n A epidemics showed that shortening the emergency vaccination response time had a greater impact on improving cost-effectiveness of vaccination than lowering the epidemic threshold for response and hence the threshold was maintained at 10 cases/100,000 in 1 week. The alert threshold was lowered from 5 to 3 cases/100,000 to improve the timeliness of response and the potential, with a good surveillance system, to bring forward vaccination as soon as possible after the epidemic threshold is crossed.  apid diagnostic tests were recommended for use n R in the investigation of meningitis outbreaks and the need to promote the development and evaluation of affordable tests was highlighted.  or treatment of suspected bacterial meningitis n F in epidemics, given the proportion (average 9%) of meningitis due to other bacterial pathogens such as Haemophilus influenzae type b and Streptococcus pneumoniae, a standard 5-day course of ceftriaxone was recommended, replacing the previous recommendation of one day treatment with oily chloramphenicol or ceftriaxone.  o change was brought to the previous n N recommendation relating to antibiotic prophylaxis: ciprofloxacin (ceftriaxone an alternative) is still recommended as a prophylactic measure for household contacts of all ages in non-epidemic periods, but not during epidemics. The risk of further regional expansion of NmC highlights the importance of continued strengthening of outbreak detection and rapid laboratory identification capacity in the region. The persistence of non-A epidemics stresses the need for the development of an affordable multivalent conjugate vaccine. Meanwhile, securing polysaccharide vaccine production and availability for outbreak response remains a necessity.

11:40  Impact of the introduction of 4CMenB vaccine on immunity during a MenB outbreak at a university in the US: epidemiology, vaccine uptake and immune response  Dr Nicole Basta, University of Minnesota, School of Public Health, Division of Epidemiology

Background: In December 2013, a novel meningococcal B vaccine (4CMenB, Bexsero®), not then licensed in the US, was offered to students at a New Jersey university to control an ongoing MenB outbreak. Evidence from the Meningococcal Antigen Typing System (MATS) and pooled sera from a clinical trial suggested that the vaccine would protect against the outbreak strain. Methods: To understand the impact of 4CMenB on immunity during the outbreak, we conducted a cross-sectional seroprevalence survey four months after vaccine introduction and a pre-/post-vaccination immunogenicity study among incoming students during the following academic year. We assessed vaccination status and collected sera to determine the proportion with serum bactericidal antibody titers using human complement (hSBA)≥4 (proportion seropositive) against the outbreak strain and against two reference strains used in vaccine development (44/76-SL [fHbp] and 5/99 [NadA]). The fHbp and NHBA components of 4CMenB were similar to those expressed by the outbreak strain. Results: In the seroprevalence study, 607 students enrolled. 66% (95% CI: 62-70%) of those who received two doses of vaccine two months apart as recommended were seropositive against the outbreak strain along with 59% (95% CI: 33-82%) of those who received only the first dose and 21% (95% CI: 6-46%) of those who remained unvaccinated. Among a random subset of participants receiving two doses as recommended but who had no detectable immunity against the outbreak strain, 87% (95% CI: 76-94) were seropositive against 44/76-SL and 100% (95% CI: 94-100) were seropositive against 5/99. Among unvaccinated participants, seropositivity was 33% (95% CI: 13-59) against 44/76-SL and 6% (95% CI: 0.1-27) against 5/99. In the pre-/post-vaccination immunogenicity study, 92 students provided paired sera. 19% (95% CI: 10-31) of those who received two doses of 4CMenB demonstrated a 4-fold rise in titers against the outbreak strain, while none of the unvaccinated exhibited a 4-fold rise (0% [95% CI: 0-11]).

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Afternoon – Thursday 5 November 2015 Conclusions: Following 4CMenB introduction to control this outbreak, no cases occurred among vaccinated students, though one case occurred in a contact. Our study is the first evaluation of the impact of 4CMenB during an ongoing outbreak. We found that immunity against the outbreak strain was lower than the immune response against two vaccine reference strains. These results present key evidence needed to inform public health policy for the future prevention and control of MenB in high-risk populations. 12:10 LUNCH, EXHIBITION AND POSTERS 13:10  Poster presentations of top 5 poster abstracts and award Chair: Prof David Lalloo, Liverpool School of Tropical Medicine 13:10 Marked improvement of Neisseria meningitidis carriage detection using PCR after overnight broth culture with parallel quantification using filter paper samples Dr Olivier Manigart, London School of Hygiene & Tropical Medicine

In addition to the well established Mendelian defects in the complement pathway that predispose to meningococcal disease, evidence from both candidate gene studies and genome wide association studies (GWAS) has identified a number of validated gene associations for susceptibility to meningococcal disease. A European consortium (EUCLIDS) supported by MRF and the European union has undertaken GWAS studies on UK, central European and Spanish cohorts, that has identified variants in the Factor H and FH related gene region that control susceptibility and resistance to disease. This talk will review recent information on fine mapping of the region to identify the causal mechanisms, and functional correlates of the gene variants. Exome sequencing is a recently available approach to identify rare variants that might influence disease susceptibility. The EUCLIDS consortium has undertaken exome sequencing on families with meningococcal disease leading to identification of novel rare variants underlying disease.

13:16 Epidemiology and surveillance of meningococcal disease in England Helen Campbell, Public Health England, London

Genes controlling severity and outcome of the disease are also being identified using the GWAS approach, and progress in identifying genes controlling outcome will also be reviewed.

13:22 Outbreak of N. meningitidis capsular group W among scouts returning from the World Scout Jamboree, Japan, 2015 Eisin McDonald,

14:15  Meningococcemia, a disease of the endothelial cells  Prof Xavier Nassif, INSERM Paris

Health Protection Scotland

13:28 Natural immunity against capsular group X N. meningitidis following an outbreak in Togo, 2007 Dr Gunnstein Norheim, Norwegian Institute of Public Health

13:34 Competition between host molecules influences susceptibility to meningococcal disease Hayley Lavender, University of Oxford 13:40 Award for the best poster

Advances from research Chair: Prof Nigel Klein, University College London 13:50  Host genetic control of susceptibility and outcome of meningococcal disease  Prof Michael Levin, Imperial College London/St Mary’s Hospital

There is now clear evidence that host genetic factors are major determinants of both susceptibility to and outcome of meningococcal disease.

Neisseria meningitidis (also known as the meningococcus) is responsible for bacteremia which can lead to meningitis after the crossing of the blood brain barrier and/or septicemia associated with a thrombotic syndrome. In mild forms this thrombotic syndrome causes limited skin purpuric lesions, in addition to the meningeal inflammation. However in more severe forms, it is responsible for extensive thrombosis and necrotic purpura associated with massive vascular leakage and shock, known as purpura fulminans. These symptoms are very uncommon in other Gram negative sepsis, thus suggesting that the pathogenesis of N. meningitidis is not just a consequence of the in vivo bacterial dissemination and/or multiplication. In vivo observations have clearly shown that Neisseria meningitidis, once in the bloodstream, interact closely with the microvessels, suggesting that the clinical specificities of meningococcal infections are correlated with its ability to colonise the microvasculature. The aim of this presentation will be to decipher the molecular mechanisms of the interaction of the bacteria with the microvasculature

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Meningitis & Septicaemia in Children & Adults 2015

Afternoon – Thursday 5 November 2015 and the consequences of this vascular colonisation responsible for the specificities of meningococcal infections. 14:40  Epidemics of Non-typhoidal Salmonella Sepsis and Meningitis in Africa  Prof Robert Heyderman, University College London

Across sub-Saharan Africa, non-typhoidal Salmonella (NTS) is a leading but under-appreciated cause of life-threatening bacterial disease among young children and HIV-infected adults. Previously widely thought of as a cause of self-limited gastroenteritis, NTS presents in these vulnerable populations both as severe sepsis and meningitis, and is associated with a case fatality that exceeds 20%. Furthermore, as pathogens such as Haemophilus influenzae type b (Hib), Neisseria meningitidis serogroup A, and Streptococcus pneumoniae are targeted by highly effective protein-conjugate vaccines, NTS is likely to become a more prominent disease control priority. We are still largely ignorant of the total burden of invasive NTS disease (iNTS), the routes of transmission and reservoirs of infection. Most iNTS in Africa is caused by Salmonella Typhimurium, Salmonella Enteritidis, and Salmonella Dublin fluctuate in prominence over time. Antimicrobial drug resistance is an increasing threat to effective case management. In western Kenya, in particular, multidrug resistant extended-spectrum βß-lactamase producing Salmonella Typhimurium has become prominent. Advances in high-throughput whole genome sequencing have allowed us to better understand the origin and epidemiology of these NTS epidemics. Although in development, NTS vaccines are unlikely to become available in the near future. 15:05 COFFEE, EXHIBITION AND POSTERS

Prevention of meningococcal disease in the UK Chair:  Prof Ian Feavers, National Institute for Biological Standards and Control

15:30  Introduction of Bexsero and MenACWY in the UK  Dr Mary Ramsay, Public Health England, London Background epidemiology: The UK has the highest incidence of invasive meningococcal disease (IMD) in Europe. In England, capsular groups B, W and Y are responsible for nearly all IMD. Routine meningococcal C (MenC) conjugate vaccination has nearly eliminated MenC IMD in England. MenB disease decreased from 2002 but remains the leading cause of IMD in the UK and a major public health problem. The introduction of Bexsero: In 2010, the Joint Committee on Vaccination and Immunisation (JCVI) convened a sub-committee to conduct a comprehensive assessment of MenB vaccine development, impact and cost-effectiveness of potential MenB immunisation strategies. In June 2013, the JCVI received a request from the Secretary of State for Health for a recommendation on the possible introduction of a routine MenB immunisation programme. The JCVI has since regularly reviewed available evidence on disease epidemiology, vaccine efficacy and safety and cost-effectiveness of a MenB immunisation programme: in March 2014, it recommended routine infant MenB immunisation following a 2+1 schedule at 2-4-12 months of age. Negotiations to procure vaccine at cost-effective price concluded in March 2015. From September 2015 the UK became the first country to offer routine vaccination against MenB disease, using Bexsero® vaccine offered routinely to babies born from July 2015. Bexsero® has the potential to prevent around 73-88% of MenB UK IMD strains. The 2-4-12 month schedule was chosen to provide maximal protection in infants before the peak at 5 months. MenB carriage in infants and toddlers is very low, so indirect protection from the programme is not expected. Delivery of this programme presents a number of challenges, in particular: the recommendation to routinely administer prophylactic paracetamol to reduce fever; the unique approach of a reduced schedule with limited catch-up and; multiple injections at each visit.

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Conference Brochure 2015 Ver 2.indd 21

26/10/2015 11:07

www.meningitis.org

Afternoon – Thursday 5 November 2015 The introduction of ACWY vaccination: Since 2009, England has experienced a steady increase in MenW IMD; initially in older adults extending to adolescents and young children. This increase was due to the emergence of a specific virulent clone (of the ST-11 clonal complex) associated with increased disease and high case fatality, most recently MenW in South America and South Africa. In 2015, PHE reported a continued increase in MenW disease across all ages and all geographical regions. The JCVI considered this situation a public health emergency. MenW incidence has been highest in infants and teenagers. Immunising infants would offer them direct protection but, because their carriage rates are low, has no wider population effect. The chosen outbreak control strategy therefore targets the highest carriers, aged 14-18 years, with Menveo® and Nimenrix® MenACWY vaccines over two years. It is important that the catch-up is completed quickly to generate herd protection and slow the rate of increase. MenACWY vaccine has also replaced MenC vaccination for University Freshers who are at increased risk of IMD. School leavers (born 1/9/ 1996-31/8/1997) have been offered MenACWY vaccine from August as an urgent catch-up campaign and MenACWY vaccine will replace the routine MenC school-based programme for 13-15 year olds this school year. Whilst the highest incidence group (infants) may not benefit for several years, evidence suggests Bexsero® may provide protection against this strain of MenW, and therefore mitigate against the immediate risk in infants. Plans for enhanced surveillance and 16:10  evaluation of efficacy of Bexsero  Prof Ray Borrow, Public Health England Vaccine Evaluation Unit, Manchester

On the 1st September 2015, Bexsero®, the meningococcal group B vaccine, was introduced into the infant immunisation schedule. Although this vaccine has been given to over 5,000 infants/ toddlers, it is newly licensed, and there are lessons to be learned as to how it will work in preventing disease against meningococcal serogroup B and other meningococcal serogroups, for example serogroup C and W. This, coupled with the introduction of meningococcal ACYW conjugate vaccine in adolescents has required for enhanced

surveillance to be initiated, full details may be found at: https://www.gov.uk/government/uploads/ system/uploads/attachment_data/file/457723/ MeningoEnhancedSurveillancePlan_01092015_ v1.1.pdf The main objectives of the surveillance for group B are to monitor the impact and age-specific vaccineeffectiveness of Bexsero® immunisation programme in children, to continue to monitor the phenotypic and genetic characteristics of invasive meningococcal isolates. All invasive meningococcal isolates are characterised by the usual phenotypic methodologies and then whole genome sequenced. Group B isolates are further investigated by the Meningococcal Antigen Typing Scheme to ascertain whether these contain antigens that are covered by Bexsero®. About 50% of cases are only confirmed through nonculture techniques, these cases are genogrouped and then two of the main vaccine antigens, PorA and factor-H binding protein, are sequenced directly from the clinical sample. Also of importance is to describe the clinical characteristics, risk factors and outcomes of invasive meningococcal disease as well as investigating the serological response in children aged