Day two abstracts

NOVARTIS SATELLITE BREAKFAST SESSION

REAL LIVES, REAL COST; THE TOLL OF MENINGOCOCCAL DISEASE

This Novartis sponsored satellite symposium will be chaired by Dr Peter Dull of Novartis Vaccines and Diagnostics and will explore the wide-reaching impacts of meningococcal disease in the UK. The symposium will start with Mr Fergal Monsell, a consultant paediatric orthopaedic surgeon. Using his first-hand experience of working with meningitis survivors, he will discuss the reality of the disease as well as treatment and associated costs. Dr Liam Dorris, a consultant neuropsychologist, will then present data from a study currently in-press regarding long-term disability, quality of life and psychosocial consequences of paediatric meningitis. Finally, Dr Stuart Clarke, a reader in infectious disease epidemiology, will examine the public health impact of meningococcal disease by presenting his own case study of an outbreak situation, discussing the response as well as associated costs. The symposium will be concluded by the chairman who will summarise the key points discussed including reference to new vaccines in development to tackle this devastating disease.

CHAIR

DR PETER DULL
NOVARTIS VACCINES AND DIAGNOSTICS, CAMBRIDGE, MA, USA

Peter Dull Dr Peter Dull is Head, Meningitis Cluster, at Novartis Vaccines and Diagnostics, where he leads clinical development activities for the Menveo® (MenACWY-CRM), Menjugate®, and a candidate meningococcal B, vaccine programmes.   

Dr Dull attended medical school at the University of Wisconsin-Madison and completed his internal medicine training at Oregon Health Sciences University in Portland, Oregon. After training as an Epidemic Intelligence Officer in the Meningitis and Special Pathogens Branch at the Centers for Disease Control and Prevention in Atlanta, Georgia, he completed subspecialty training in infectious diseases at Emory University in Atlanta. He joined Chiron Vaccines (now Novartis Vaccines and Diagnostics) in 2004.   

Dr Dull’s research areas have included meningococcal meningitis outbreak investigations and vaccination implementation strategies in the United States and Africa, oropharyngeal carriage of Neisseria meningitidis associated with the Hajj, and molecular diagnostics of bacterial meningitis.    

PANEL

MR FERGAL MONSELL, MSc PHd FRCS(Orth)
ROYAL HOSPITAL FOR CHILDREN

IMMEDIATE IMPACT: MUSCULO-SKELETAL IMPACTS OF MENINGOCOCCAL DISEASE


Fergal Monsell Mr Fergal Monsell has been a Consultant Paediatric Orthopaedic Surgeon at the Royal Hospital for Children, Bristol since 2005. He worked in the same capacity at The Hospital for Sick Children, Great Ormond Street and The Royal National Orthopaedic Hospital, Stanmore between 1997 and 2005.

He completed his higher surgical training at the University of Manchester and fellowship training at the Royal Alexandra Hospital for Children, Sydney, Australia. He has a broad based practice with a special interest in limb reconstruction surgery using a spectrum of contemporary techniques. He has considerable experience in the management of patients with the skeletal consequences of septicaemia and contributes to a multi-disciplinary team specifically managing this patient group. He is active in all aspects of paediatric trauma and has published on this subject.

He has an active clinical and basic science research portfolio and received a Doctorate of Philosophy in 2010, defending a thesis that explored the effect of chemotherapy on regenerate bone formation in distraction osteogenesis.

DR LIAM NORRIS
CONSULTANT PAEDIATRIC NEUROPSYCHOLOGIST AND HONORARY SENIOR CLINICAL LECTURER, ROYAL HOSPITAL FOR SICK CHILDREN, GLASGOW

SOCIETAL IMPACT: PSYCHOSOCIAL IMPACTS OF MENINGOCOCCAL DISEASE

Liam Norris Dr Dorris has been a Consultant Paediatric Neuropsychologist at RHSC Glasgow since 2005, with prior appointments within NHS Greater Glasgow as a Clinical Psychologist in neurosciences, community child health and also as clinical lecturer at the Department of Psychological Medicine, University of Glasgow. He has published widely in several areas of child disability and neurological disorder and has active research interests in acquired brain injury, epilepsy and sleep disorders.

DR STUART C CLARKE
READER IN INFECTIOUS DISEASE EPIDEMIOLOGY AND HONORARY CONSULTANT IN HEALTH PROTECTION, UNIVERSITY OF SOUTHAMPTON, UK

PUBLIC HEALTH IMPACT: MENINGOCOCCAL DISEASE OUTBREAKS

Stuart C Clarke Dr Clarke is Reader in Infectious Disease Epidemiology and Honorary Consultant in Health Protection. He has a major interest in the epidemiology of infectious diseases, particularly in relation to vaccine development and the evaluation of new vaccines.

Dr Clarke developed his independent research career when Director of the Scottish Meningococcus and Pneumococcus Reference Laboratory between 1998 and 2004. His research focuses on the molecular epidemiology of vaccine-preventable bacterial infections. He is also a member of the Biofilm and Microbial Communities group in Southampton where he provides an essential link between epidemiology and microbial communities. Dr Clarke was involved in the national meningococcal carriage study, led by Professors Martin Maiden and James Stuart, which was mainly funded by the Wellcome Trust. He is now involved in various pneumococcal and meningococcal carriage studies.

Dr Clarke has published more than 80 peer-reviewed papers mainly in the field of N. meningitidis and S. pneumoniae infection. In 2009, Dr Clarke won the Bupa Foundation's award of ‘best emerging medical researcher in the UK’ for his work on the molecular epidemiology of pneumococcal infection around the introduction of pneumococcal conjugate vaccines.

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Session 1: Tackling meningitis in Africa



CHAIR

PROFESSOR ROBERT HEYDERMAN
MALAWI-LIVERPOOL-WELLCOME TRUST

REDUCING THE VERY HIGH MORTALITY FOR ADULT MENINGITIS IN AFRICA

Robert Heyderman Rob Heyderman is Professor of Tropical Medicine and Director of the Malawi-Liverpool-Wellcome Trust Clinical Research Programme. He trained in London and Zimbabwe. His current research interests comprise the endothelial biology, coagulopathy and immunology of severe infection; the development of naturally acquired immunity to Neisseria meningitidis and Streptococcus pneumoniae; regulation of the host inflammatory response; and the clinical diagnosis and management of meningitis and septicaemia. Current initiatives include new approaches to mucosal vaccination to prevent pneumonia and meningitis both in the UK and in the tropics; management of meningitis and severe sepsis in resource-poor settings; and microbial genetic diversity in the contact of HIV infection.
DR MARC LAFORCE
MENINGITIS VACCINE PROJECT, PATH/WHO, FERNEY-VOLTAIRE, FRANCE

INTRODUCTION OF MENINGOCOCCAL SEROGROUP A VACCINE IN THE AFRICAN MENINGITIS BELT

Marc LaForce Dr Marc LaForce joined the Meningitis Vaccine Project as Director in August 2001. He has a long and distinguished career in disease prevention, vaccinology, and international health. The Meningitis Vaccine Project is a partnership between WHO and PATH aimed at developing, testing, licensing and introducing conjugate meningococcal vaccines in Sub-Saharan Africa. Dr LaForce earned his Doctor of Medicine degree from Seton Hall College of Medicine and Dentistry in Jersey City, NJ. He completed his internal medicine and infectious disease training on the Harvard Service at Boston City Hospital. After serving as an Epidemic Intelligence Service Officer in the Meningitis and Special Pathogen units at the Centers for Disease Control and Prevention he joined the faculty at the University of Colorado School of Medicine. He is board certified in internal medicine and infectious diseases and is a Fellow of the American College of Physicians and the Infectious Diseases Society of America. Before joining PATH he was Physician-in-Chief at the Genesee Hospital and Professor of Medicine at the University of Rochester School of Medicine and Dentistry in Rochester, NY.

Dr LaForce has published over 170 papers and book chapters chiefly in the areas of pulmonary defence mechanisms, clinical infectious diseases, epidemiology and vaccinology.

ABSTRACT

A new Group A meningococcal (Men A) conjugate vaccine, MenAfriVacTM, was prequalified by the World Health Organization (WHO) in June 2010. Because Burkina Faso has repeatedly suffered meningitis epidemics due to Group A Neisseria meningitidis special efforts were made to conduct a country-wide campaign with the new vaccine in late 2010 and before the January 2011 onset of the next epidemic meningococcal disease season. In the ensuing five months (July–November 2010) the following challenges were successfully managed: 1) doing a large safety study and registering the new vaccine in Burkina Faso; 2) developing a comprehensive communication plan; 3) strengthening the surveillance system with particular attention to improving the capacity for real-time polymerase chain reaction (PCR) testing of spinal fluid specimens; 4) improving cold chain capacity and waste disposal; 5) developing and funding a sound campaign strategy; and 6) ensuring effective collaboration across all partners. Each of these issues required specific strategies that were managed through a WHO-led consortium that included all major partners (Ministry of Health/Burkina Faso, Serum Institute of India Ltd., UNICEF, Global Alliance for Vaccines and Immunisation, Meningitis Vaccine Project, CDC/Atlanta, and the Norway Institute of Public Health/Oslo). The new meningococcal A conjugate vaccine was introduced on December 6, 2010, in a national ceremony led by His Excellency Blaise Compaore, the President of Burkina Faso. The ensuing 10-day national campaign was hugely successful, and over 11.4 million Burkinabes between the ages of 1 and 29 years (100% of target population) were vaccinated. African national immunization programs are capable of achieving very high coverage for a vaccine desired by the public, introduced in a well-organized campaign, and supported at the highest political level. The Burkina Faso success augurs well for further rollout of the Men A conjugate vaccine in meningitis belt countries.

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DR CAROLINE TROTTER
UNIVERSITY OF BRISTOL

CARRIAGE AND SPREAD OF MENINGOCOCCUS IN THE MENINGITIS BELT

Caroline Trotter Dr Caroline Trotter is a Senior Research Fellow in the School of Social and Community Medicine at the University of Bristol. She is an infectious disease epidemiologist, with an MSc and PhD from the London School of Hygiene and Tropical Medicine. Her research focuses on assessing the population impact of vaccination against meningococcal and pneumococcal disease, using a range of research methods including mathematical modelling, cost- effectiveness studies, analyses of large databases and seroprevalence studies. She is currently working on the MenAfriCar project (www.menafricar.org).

ABSTRACT

MenAfriCar (the African Meningococcal Carriage Consortium) is a global research effort to study how meningococci are spread in Africa, and to document the impact of a new meningitis vaccine (MenAfriVac) on reducing transmission.

Carriage and seroprevalence studies are being conducted in seven countries across the meningitis belt: Ethiopia, Chad, Niger, Nigeria, Mali, Ghana and Senegal, in collaboration with the London School of Hygiene and Tropical Medicine and 11 other international centres. The first cross sectional carriage surveys of 2,000 individuals per country (5,000 in Mali and Niger, where MenAfriVac campaigns began at the end of 2010) in rural and urban sites were performed in the rainy season between September and December 2010. Detailed longitudinal studies were also performed in households where a carrier was identified to examine rates of acquisition and loss and describe patterns of transmission within households.

Preliminary results from the first cross-sectional surveys will be presented, including risk factors for carriage. The prevalence of meningococcal carriage overall was low at around 4% and serogroup A carriers were only identified in Chad. The implications of these results for the design of the subsequent stages of the study will be discussed. Several methodological challenges were encountered, including difficulties with serogrouping using slide agglutination, and implementation of a new data management system. A brief update on the current activities in the second round of surveys will also be given.

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PROFESSOR RICHARD ADEGBOLA
BILL AND MELINDA GATES FOUNDATION

BILL AND MELINDA GATES FOUNDATION ACTIVITY TO COMBAT MENINGITIS IN AFRICA

Richard Adegbola Dr Richard Adegbola joined the Bill & Melinda Gates Foundation in 2009 as Senior Program Officer and lead for Pneumonia Clinical Studies, coming from 19 years with the UK Medical Research Council (MRC) Unit in The Gambia. There he was Head of Bacterial Diseases Programme, with a focus on bacterial infections including pneumonia, meningitis and tuberculosis research. His work there included a Phase IV Hib vaccine effectiveness study, and the pneumococcal vaccine efficacy trial that demonstrated a 16% reduction in childhood mortality as a result of pneumococcal vaccination. Results from these studies have provided pivotal evidence for the large scale uptake of these new vaccines. His current interests include the bacteriology of large vaccine efficacy trials, herd effect of conjugate vaccines and maternal immunization as a strategy for prevention of microbial infection in young infants.

Dr Adegbola received his undergraduate education in medical microbiology at the Lagos University Teaching Hospital in Nigeria and obtained his Ph.D. in Microbiology from University of Dundee, Scotland. He is a Fellow of the Royal College of Pathologists, London (in Medical Microbiology) and an Honorary Fellow of the Royal College of Physicians, London. The University of Leicester, UK appointed him an Honorary Visiting Professor on 1 May 2005. He has over 20 years research experience with over 167 journal publications and 5 book chapters in bacterial infections of the tropics particularly, pneumonia and meningitis, caused by Streptococcus pneumoniae, Haemophilus influenzae type b and Neisseria meningitidis in young children.

At the Gates Foundation, Dr Adegbola’s role is taking pneumonia and meningitis research findings to policy, implementation and evaluation for impact. He is responsible for vaccine impact studies, including impact evaluations for pneumococcal and meningococcal conjugate vaccines and maternal immunization program and for studies of the microbial causes of pneumonia and meningitis in the developing world.

ABSTRACT

For more than a century, meningococcal group A epidemics have swept across the African meningitis belt stretching from Senegal in the west to Ethiopia in the east with apparently unstoppable force. With each epidemic, the disease decimates communities, killing about 10% of affected people, leaving 25% of survivors with sequelae such as brain damage or deafness and rendering a struggling health care system completely overwhelmed. A population of 400 million is at risk of this disease and children as well as adults can be infected by meningitis epidemics.

Polysaccharide vaccines against meningococcal serogroups A, C, Y and W135 have been available for over 20 years but the vaccines are used for re-active mass vaccination campaigns along with antimicrobial treatments for epidemic containment only. They neither provide long-lasting protection nor confer herd immunity, particularly in young children who are at highest risk for disease. A quadrivalent protein-polysaccharide conjugate vaccine containing meningococcal serogroups A, C, Y and W135 and monovalent group C conjugate vaccine with a more lasting protection against meningococcal disease have been introduced in developed countries but these vaccines are at a cost that is unaffordable at settings with a poor resource base.

In 1996 there occurred a most devastating epidemic in the African meningitis belt with 200,000 cases and 20,000 deaths with as yet undisclosed number of survivors with sequelae. This generated a major concern among the public health officials of the affected communities to which they drew a global attention. Consequently the Meningitis Vaccine Project (MVP), a partnership between WHO and PATH, was formed with funding from the Gates Foundation in 2001 to address the prevention and ultimately the elimination of epidemic meningitis in Sub-Saharan Africa. The vision was to:

  • Develop a meningococcal conjugate vaccine and evaluate it in Africa
  • Create a pathway for the licensure of vaccine to be used largely in Africa
  • Assure production in sufficient volume to meet projected needs
  • Monitor throughout to assure the effectiveness and safety of the intervention
  • Finance the procurement of vaccine through existing or new global programs
  • Introduce the vaccine through mass and routine immunization programs in synergy with other public health programs.
The Goal was to eliminate epidemic meningitis in Africa as a public health problem through the development, testing, licensure and widespread use of conjugate meningococcal vaccines at a cost that is affordable in the affected countries in the meningitis belt.

After 10 years of Research and Development including safety, immunogenicity and antibody persistence studies and a process of licensure in India and WHO pre-qualification in June 2010, MenAfriVac™ became the first vaccine developed specifically for a poor population at a cost of approximately $1 to purchase and deliver. In December 2010, people across Burkina Faso, Mali, and Niger became the first to receive the vaccine with highly promising effects. Preparations are underway for MenAfriVac™ introduction to the remaining countries and for studies aimed at collecting data required for licensure for infant indication.

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Session 2: Current issues in recognition and treatment



CHAIR

DR SIMON NADEL
ST MARY'S HOSPITAL, IMPERIAL COLLEGE LONDON

Simon Nadel Simon Nadel has been a Consultant in Paediatric Intensive Care since 1994. Prior to this he trained in paediatric infectious diseases. He has been involved in coordinating and running therapeutic trials in children with meningococcal and other septic shock, and has taken part in research studies into the pathophysiology, treatment and outcome of meningococcal disease in children. He has been involved in writing clinical guidelines for the management of children with septicaemia and meningitis.
DR NELLY NINIS
ST MARY'S HOSPITAL, IMPERIAL COLLEGE LONDON

PITFALLS IN RECOGNITION OF MENINGITIS AND SEPTICAEMIA IN TEENAGERS
 
Nelly Ninis Dr Nelly Ninis is currently a consultant in General Paediatrics at St Mary’s Hospital, Paddington. She has completed training in paediatric infectious diseases and immunology and has an Msc in tropical medicine. She worked for three years on the Paediatric Intensive Care Unit at St Mary’s when it was a specialist referral unit for meningococcal sepsis. She conducted the RCPCH study on healthcare delivery and the outcome of meningococcal disease in children, funded by Meningitis Research Foundation. From this study she has developed an interest in the way sepsis is diagnosed both in primary and secondary care. Dr Ninis is also a part of the National Institute for Health and Clinical Excellence (NICE) Guideline Development Group for Meningitis and Septicaemia.

ABSTRACT

There have been great improvements in the medical management of children with meningitis and septicaemia over the past 15 years. Paediatricians in the UK have become united in managing sepsis in a standardised way. Meningococcal disease is no longer accepted to be an invariably fatal condition, 20 years of research has resulted in evidence-based protocols and MRF has been particularly instrumental in ensuring that this work is disseminated widely.

Similarly in the adult based world, the Surviving Sepsis Campaign has produced protocols for improving the outcome from sepsis in adults.

But how about the grey area of late adolescence? It is known that older teenagers have increased rates of meningococcal disease and higher case fatality rates than younger children. It is also known that teenagers are undergoing a metamorphosis from childhood to adulthood with physical changes occuring both in their bodies and brains. Socially teenagers can be difficult and this may affect the way diseases are recognised in this age group.

The impact of a major disease such as meningococcal disease in teenagers can be profound. Sequelae are not only physical but also emotional, educational and social. These outcomes are worse than for younger children. Follow up rates in teenagers are also poor.

Are all these problems due to the teenagers themselves or do we as medics contribute to the poor outcomes?

Who should manage a 16 and a half year old who is still in school? A paediatrician or an adult physician? Are they always taken seriously when they present. Do they present late to doctors as it is assumed they are hungover or just being wimps? Does the fact they are able to compensate well in sepsis make recognition of disease severity more difficult?

I would like to propose that we set up an adolescents sepsis UK task force to set standards for the care of adolescents with sepsis and particularly meningococcal disease. We need to bring together experts in paediatric and adult intensive care and adolescent physcians to mount a campaign to raise the profile of young people with sepsis. As I am actually not an expert in any of these fields, I propose to take the minutes and make the coffee! I welcome your interest.

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DR MARK PETERS
INSTITUTE OF CHILD HEALTH, UNIVERSITY COLLEGE LONDON

OVERVIEW OF EVIDENCE FOR MANAGING CHILDREN WITH SEPSIS, INCLUDING FLUID MANAGEMENT OF CHILDREN IN SHOCK

Mark Peters Dr Mark Peters is Senior Lecturer in Paediatric Intensive Care at the Institute of Child Health, UCL and Hon. Consultant at Great Ormond Street Hospital and The Children's Acute Transport Service. His research interests started in laboratory studies in innate immunity and cellular adhesion and have developed into clinical studies in children with critical illnesses including trauma, sepsis and respiratory failure. He chairs the Paediatric Intensive Care Society Study Group and the Medicines for Children Research Network Clinical Studies Group for Anaesthesia, Pain, Intensive Care and Cardiology.

ABSTRACT

Observational studies in septic shock associate improvements in outcome with early and rapid fluid resuscitation. Adoption of protocols recommending >40mls/kg volume expansion in the first hour of in-hospital resuscitation, prior to intensive care may be crucial. Human albumin solution may be preferable to saline – perhaps because of a greater degree of volume expansion per administered volume. Adult and paediatric randomised trial data support the use of objective summary measures of the adequacy of oxygen delivery (ScvO2 or lactate clearance) to guide resuscitation. These studies imply that traditional goals of heart rate, blood pressure and perfusion are inadequate and more fluid and more inotrope therapy may rescue more patients. The very early septic shock deaths seen in the UK may be improved by simple adherence to existing protocols.

This standard view of the critical role of fluid resuscitation has been challenged recently by trial data from resource-limited settings. There are numerous possible explanations why cost and benefit of fluid resuscitation might differ widely in different populations but these data remind us of the poor evidence base on which our current practice is based. We need high quality studies of fluid resuscitation in critically ill children.

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PROFESSOR MERVYN SINGER
UNIVERSITY COLLEGE LONDON

CURRENT ADVANCES IN SEPSIS MANAGEMENT IN ADULTS
 
Mervyn Singer Mervyn Singer is Professor of Intensive Care Medicine at University College London. He has a major research interest in sepsis and multi-organ failure and champions the key role of mitochondria in causing organ dysfunction. He is an NIHR Senior Investigator and his research is funded by the Wellcome Trust, MRC, EU and NIHR. He has had major involvement in a number of multi-centre trials related to sepsis such as CORTICUS, PAC-MAN and ProMISe.

ABSTRACT

 
Outcomes continue to improve though this appears more related to enhancements in the general process of care rather than specific innovations. High-profile campaigns have promoted early identification of sepsis and generic management guidelines though, of note, the reduction in mortality rates seem to have occurred outwith. To my mind, this highlights a dilemma of which we are becoming increasingly aware, namely that our drugs and technologies have considerable power to, if not save, then at least prolong life yet, by the same token, have a powerful ability to cause harm. The detrimental effects are, however, subtle and rarely apparent at 'the end of the bed'. Our current lack of sophistication in immune, hormonal and metabolic monitoring fails to detect these covert changes. This monitoring deficiency may also be responsible in large part for the repeated failure of high-profile and high-expense multi-centre trials attempting to modulate the immune process. Thus, the frequent inability to Prof Mervyn S nger deliver the right dose to the right patient at the right time and for the right duration may contribute to the overall neutral or even negative outcomes of these studies. The subsets who may have benefitted are diluted or cancelled out by those where it did not deliver a positive effect. There is a considerable push at present to develop novel biomarkers to identify infection, sepsis and organ dysfunction at an early stage, and to prognosticate. This will probably assist greatly in identifying appropriate patients for treatment. This will also be allied with a greater appreciation of the pathophysiology underlying sepsis, and recognition that many seemingly 'negative' consequences may actually represent intrinsic attempts at adaptation which should be perhaps supported rather than reversed by our management.

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Session 3: Prevention of meningococcal disease



CHAIR

PROFESSOR RAY BORROW
VACCINE EVALUATION UNIT, HEALTH PROTECTION AGENCY, MANCHESTER

Ray Borrow Prof Ray Borrow is Head of the Vaccine Evaluation Unit at the Health Protection Agency (HPA) North West, Manchester, UK, where he is responsible for the evaluation of serological responses to various bacterial and viral vaccines with a special interest in meningococcal and pneumococcal vaccines. He is also the Deputy Head of the HPA Meningococcal Reference Unit for England & Wales. He gained his PhD in 1994, his MRCPath in 2003, became an Honorary Professor of Vaccine Preventable Diseases at the University of Manchester in 2009 and Visiting Professor of the Manchester Metropolitan University in 2011. His scientific findings resulted in over 190 peer reviewed published papers. He serves as a member of the DoH Joint Committee on Vaccination and Immunisation (JCVI) and frequently advises WHO and companies on both meningococcal and pneumococcal vaccines. He sits on the medical-scientific advisory panels for Meningitis Research Foundation, Meningitis UK and Meningitis Trust.
PROFESSOR ANDREW POLLARD
UNIVERSITY OF OXFORD

CHANGES TO THE UK IMMUNISATION PROGRAMME, INCLUDING PROSPECTS FOR A TEENAGE MENINGOCOCCAL BOOSTER

Andrew Pollard Andrew J Pollard, FRCPCH PhD, is Professor of Paediatric Infection and Immunity at the University of Oxford, Director of the Oxford Vaccine Group, James Martin Senior Fellow, Jenner Institute Investigator, Fellow of the Infectious Disease Society of America, Fellow of St Cross College and Honorary Consultant Paediatrician at the Children’s Hospital, Oxford, UK. He obtained his medical degree at St Bartholomew’s Hospital Medical School, University of London in 1989 and trained in paediatrics at Birmingham Children’s Hospital, UK, specialising in Paediatric Infectious Diseases at St Mary’s Hospital, London, UK and at British Columbia Children’s Hospital, Vancouver, Canada. He obtained his PhD at St Mary’s Hospital, London, UK in 1999 studying immunity to Neisseria meningitidis in children and proceeded to work on anti-bacterial innate immune responses in children in Canada before returning to his current position at the University of Oxford, UK in 2001. He chaired the UK’s NICE meningitis guidelines development group, and chairs the NICE topic expert group developing quality standards for management of meningitis and meningococcal septicaemia. He sits on the Department of Health committee that considers use of meningococcal vaccines. He runs one of the largest paediatric research groups in the UK with 70 staff. Current research activities include clinical trials of new and improved vaccines for children, surveillance of invasive bacterial diseases in children in Nepal, studies of cellular and humoral immune responses to glycoconjugate and typhoid vaccines, and development of a serogroup B meningococcal vaccine. His publications include over 200 manuscripts and books on various topics in paediatrics, infectious diseases, and high altitude medicine.

ABSTRACT

Since the implementation of a serogroup C meningococcal (MenC) vaccine programme in the UK 12 years ago, there have been a number of changes to the immunisation schedule designed to improve individual and population protection against bacterial meningitis and meningococcal septicaemia. The introduction of boosters at 12 months of age for Haemophilus influenzae type b (Hib) and MenC in 2006 and a reduction in the number of priming doses for MenC were undertaken in attempt to defend and sustain protection through early childhood. Whilst this approach appears to have been especially successful for Hib, MenC antibody wanes rapidly after the booster. With the highest rates of Hib carriage being in childhood, high antibody levels in the first few years of life both protect the individual and provide herd immunity by blocking Hib transmission, with the result that Hib disease is once again at a very low incidence. However, meningococcal carriage peaks in adolescence and early adulthood, and so strategies to sustain immunity at this age are being evaluated on both sides of the Atlantic to protect the individual from disease and block transmission of this organism to other cohorts (both older and younger) who remain susceptible. Strategies using either MenC or MenACYW vaccines could be considered. Maintaining Hib, and MenC immunity amongst the segment of the population responsible for transmission of the organism is essential for public health in the long term.

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DR PAUL CLEARY
HPA NORTHWEST, LIVERPOOL

DEALING WITH A LOCALISED MENB EPIDEMIC - THE CUMBRIAN SITUATION

Paul Cleary Paul is a medical epidemiologist who joined the HPA in 2009. After several years as a hospital physician and periods working in epidemiological research in the UK and abroad, he retrained in public health and epidemiology. Since becoming HPA NW regional epidemiologist he has led the epidemiological investigation of a number of regional and national infectious disease outbreaks. His current research projects relate to Clostridium difficile and influenza and he has an ongoing interest in the use of advanced statistical methods in epidemiology.

ABSTRACT

Invasive group B meningococcal disease remains a cause of significant morbidity and mortality in the United Kingdom. Most disease occurs sporadically but localised outbreaks occur, and available public health interventions are limited. Dr Cleary will describe the investigation and public health response to a cluster of invasive meningococcal disease in West Cumbria in early 2011 against the background of the wider epidemiology of invasive group B meningococcal disease and describes a meningococcal carriage prevalence study undertaken in West Cumbria to attempt to better understand the transmission of disease in this setting.

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Session 4: Prospects for prevention of meningococcal disease



CHAIR

PROFESSOR IAN FEAVERS
NATIONAL INSTITUTE FOR BIOLOGICAL STANDARDS AND CONTROL

Ian Feavers Ian Feavers, PhD, is Head of the Division of Bacteriology at the NIBSC, UK. He studied for his PhD at the University of Newcastle upon Tyne, eventually moving to NIBSC after periods of postdoctoral research at the University of Sheffield and the Friedrich Miescher Institut in Basel. During the late 1990s, when new conjugate vaccines were being introduced, he headed the laboratory responsible for the control and standardisation of meningococcal and pneumococcal vaccines. Ian continues to oversee an active research programme on the molecular genetics and immunology of meningococcal and pneumococcal antigens. Because of his broad experience of bacterial vaccines and molecular biology, he has been closely involved with a number of meningococcal vaccine developments. He regularly contributes to WHO and EU guidelines, serves as one of NIBSC’s representatives on the Vaccine Working Party of the EMA, and is a member of the JCVI subgroup on meningococcal vaccines. Ian teaches on a number of vaccine related courses in the University of London and is a Visiting Professor at Imperial College.
DR PETER DULL
NOVARTIS VACCINES AND DIAGNOSTICS, CAMBRIDGE, MA, USA

PROSPECTS FOR USE OF NOVARTIS 4CMENB VACCINE

Peter Dull Dr Peter Dull is Head, Meningitis Cluster, at Novartis Vaccines and Diagnostics, where he leads clinical development activities for the Menveo® (MenACWY-CRM), Menjugate®, and a candidate meningococcal B, vaccine programmes.   

Dr Dull attended medical school at the University of Wisconsin-Madison and completed his internal medicine training at Oregon Health Sciences University in Portland, Oregon. After training as an Epidemic Intelligence Officer in the Meningitis and Special Pathogens Branch at the Centers for Disease Control and Prevention in Atlanta, Georgia, he completed subspecialty training in infectious diseases at Emory University in Atlanta. He joined Chiron Vaccines (now Novartis Vaccines and Diagnostics) in 2004.   

Dr Dull’s research areas have included meningococcal meningitis outbreak investigations and vaccination implementation strategies in the United States and Africa, oropharyngeal carriage of Neisseria meningitidis associated with the Hajj, and molecular diagnostics of bacterial meningitis.   

ABSTRACT

The variability of expression of serogroup B immunodominant surface proteins, coupled with the poor immunogenicity of the MenB capsule, have prevented the successful introduction of a broadly protective MenB vaccine. Vaccines tailormade to specific MenB strains have been developed to control epidemic outbreaks caused by specific MenB clones. In New Zealand, an outer membrane vesicle-based MenB vaccine (MeNZB) has proven effective in all age groups, including infants, after its introduction in 2004. As approaches using standard Pasteur principles to develop a universal MenB vaccine have so far been unsuccessful, utilising a novel ‘reverse vaccinology’ technique, Novartis Vaccines has identified multiple new vaccine targets and incorporated them into a multicomponent vaccine, 4CMenB (Bexsero™). Phase 3 clinical trials have been completed and an application for licensure was submitted in Europe in December 2010 which included data from over 5000 infants and 1500 adolescents. Recently available clinical data will be reviewed as well as updates provided on the regulatory status of the vaccine.

DR KATHRIN U JANSEN
PFIZER INC, NY, USA

PFIZER STRATEGY FOR PREVENTION OF MENINGOCOCCAL B DISEASE

Katherin Jansen Kathrin U Jansen, PhD is a Senior Vice President at Pfizer’s Pearl River, NY campus. She has responsibility for the scientific management of vaccine research and early development including management responsibilities for all vaccines clinical testing.

She received her doctoral degree in Microbiology, Biochemistry & Genetics from Phillips Universitat, Marburg, Germany, in 1984. Following completion of her formal training and postdoctoral work at the Institute for Mikrobiologie in Marburg, Dr Jansen continued her training with Professor GP Hess at Cornell University working on the expression of the acetylcholine receptor in yeast for structural and functional studies. She then joined the Glaxo Institute for Molecular Biology in Geneva, Switzerland where she focused on basic studies of a receptor believed to be a drug target to treat allergies.

In 1992 Dr Jansen moved to the Merck Research Laboratories. During the following 12 years she directed a number of vaccine research efforts, including Merck’s novel bacterial vaccine programs. She initiated Merck’s vaccine program for the prevention of human papillomavirus infection (HPV). She played a central role in the vaccine’s design, the development of novel HPV clinical diagnostic assays, clinical trial designs, the study of the virus’ epidemiology, and the entry of the vaccine into definitive clinical trials. Her efforts led to the licensure of the world’s first cervical cancer vaccine (Gardasil®).

Dr Jansen left Merck in October 2004 to join VaxGen as Chief Scientific Officer and Senior Vice President for Research and Development with responsibility for VaxGen’s anthrax and smallpox vaccine programs. In 2006 she joined Wyeth (now Pfizer) as a Senior Vice President to lead the vaccine research, early development and clinical testing groups.

Dr Jansen was appointed an Adjunct Professor at the University of Pennsylvania School of Medicine in 2010. She brings a recognised series of accomplishments, as well as an established international reputation in vaccine discovery research and development.

ABSTRACT

Pfizer is developing a bivalent factor H binding protein (fHBP/LP2086) vaccine to prevent Neisseria meningitidis serogroup B (MnB) disease. fHBP, an outer membrane lipoprotein, protects MnB from complement attack. More than 2,500 invasive MnB disease isolates in addition to carriage isolates have been studied. IMDB and carriage isolates all contain the fhbp gene. The fHBP protein sequences segregate into two immunologically distinct subfamilies, A and B. Preclinical studies identified the importance of including one lipidated protein from each subfamily into the vaccine to achieve robust serum bactericidal antibody responses and broad coverage of disease isolates. Vaccine coverage in the context of fHBP sequence diversity is an important consideration for licensure, and post-licensure surveillance with appropriate surveillance mechanisms. fHBP sequences, expression levels, patient age and epidemiological markers were analyzed for MnB invasive isolates. Breadth of vaccine coverage was evaluated by hSBA using bivalent, rLP2086 immune sera from phase 2 studies conducted in adolescents ages 11 – 18 and young adults. A method to bridge hSBA responses from a limited number of IMDB isolates to a wider panel of MnB isolates was developed.

The bivalent, rLP2086 vaccine candidate induced robust hSBA responses against diverse MnB strains. Clinical data from phase I/II will be reviewed in the context of epidemiological studies. Bridging data to epidemiologically important IMDB isolates will also be presented.

The bivalent, rLP2086 investigational vaccine confers broad seroprotection against diverse MnB invasive strains. Efficacy will be determined and monitored using hSBA responses (surrogate for protection) with invasive MnB strain expressing heterologous (compared to vaccine) fHBP sequences.

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INTERACTIVE SESSION: IMPLEMENTING A MENB VACCINE

This interactive session, involving a panel of experts in the fields of vaccine development, epidemiology, clinical management and research, will discuss the issues surrounding the introduction ofa MenB vaccine into the UK immunisation schedule. Questions on all aspects of MenB vaccine implementation are invited from the audience as part of this ‘Any Questions’ style session.

MODERATOR

PROFESSOR ANDREW POLLARD
UNIVERSITY OF OXFORD

Andrew Pollard Andrew J Pollard, FRCPCH PhD, is Professor of Paediatric Infection and Immunity at the University of Oxford, Director of the Oxford Vaccine Group, James Martin Senior Fellow, Jenner Institute Investigator, Fellow of the Infectious Disease Society of America, Fellow of St Cross College and Honorary Consultant Paediatrician at the Children’s Hospital, Oxford, UK. He obtained his medical degree at St Bartholomew’s Hospital Medical School, University of London in 1989 and trained in paediatrics at Birmingham Children’s Hospital, UK, specialising in Paediatric Infectious Diseases at St Mary’s Hospital, London, UK and at British Columbia Children’s Hospital, Vancouver, Canada. He obtained his PhD at St Mary’s Hospital, London, UK in 1999 studying immunity to Neisseria meningitidis in children and proceeded to work on anti-bacterial innate immune responses in children in Canada before returning to his current position at the University of Oxford, UK in 2001. He chaired the UK’s NICE meningitis guidelines development group, and chairs the NICE topic expert group developing quality standards for management of meningitis and meningococcal septicaemia. He sits on the Department of Health committee that considers use of meningococcal vaccines. He runs one of the largest paediatric research groups in the UK with 70 staff. Current research activities include clinical trials of new and improved vaccines for children, surveillance of invasive bacterial diseases in children in Nepal, studies of cellular and humoral immune responses to glycoconjugate and typhoid vaccines, and development of a serogroup B meningococcal vaccine. His publications include over 200 manuscripts and books on various topics in paediatrics, infectious diseases, and high altitude medicine.

PANEL

PROFESSOR RAY BORROW
VACCINE EVALUATION UNIT, HEALTH PROTECTION AGENCY, MANCHESTER

Ray Borrow Prof Ray Borrow is Head of the Vaccine Evaluation Unit at the Health Protection Agency (HPA) North West, Manchester, UK, where he is responsible for the evaluation of serological responses to various bacterial and viral vaccines with a special interest in meningococcal and pneumococcal vaccines. He is also the Deputy Head of the HPA Meningococcal Reference Unit for England & Wales. He gained his PhD in 1994, his MRCPath in 2003, became an Honorary Professor of Vaccine Preventable Diseases at the University of Manchester in 2009 and Visiting Professor of the Manchester Metropolitan University in 2011. His scientific findings resulted in over 190 peer reviewed published papers. He serves as a member of the DoH Joint Committee on Vaccination and Immunisation (JCVI) and frequently advises WHO and companies on both meningococcal and pneumococcal vaccines. He sits on the medical-scientific advisory panels for Meningitis Research Foundation, Meningitis UK and Meningitis Trust.

PROFESSOR IAN FEAVERS
NATIONAL INSTITUTE FOR BIOLOGICAL STANDARDS AND CONTROL

Ian Feavers Ian Feavers, PhD, is Head of the Division of Bacteriology at the NIBSC, UK. He studied for his PhD at the University of Newcastle upon Tyne, eventually moving to NIBSC after periods of postdoctoral research at the University of Sheffield and the Friedrich Miescher Institut in Basel. During the late 1990s, when new conjugate vaccines were being introduced, he headed the laboratory responsible for the control and standardisation of meningococcal and pneumococcal vaccines. Ian continues to oversee an active research programme on the molecular genetics and immunology of meningococcal and pneumococcal antigens. Because of his broad experience of bacterial vaccines and molecular biology, he has been closely involved with a number of meningococcal vaccine developments. He regularly contributes to WHO and EU guidelines, serves as one of NIBSC’s representatives on the Vaccine Working Party of the EMA, and is a member of the JCVI subgroup on meningococcal vaccines. Ian teaches on a number of vaccine related courses in the University of London and is a Visiting Professor at Imperial College.

PROFESSOR ADAM FINN
UNIVERSITY OF BRISTOL


Prof Adam Finn Professor Adam Finn is Head of the Academic Unit of Child Health at Bristol Medical School, Dept of Clinical Science South Bristol and an honorary consultant in paediatric infectious diseases and immunology at Bristol Royal Hospital for Children. He is director of the South West Medicines for Children Research Network and heads the Bristol Children's Vaccine Centre. He trained in Infectious Diseases at the Children's Hospital of Philadelphia and in Immunology at the Institute of Child Health in London where he obtained his PhD.

He worked in Sheffield between 1992 and 2001 where he was involved in several trials of meningococcal group C and other vaccines. His current main research interest is the mucosal immune response to respiratory bacteria including pneumococcus and meningococcus.

DR NICK KITCHIN
SENIOR DIRECTOR, VACCINE CLINICAL RESEARCH, PFIZER


Dr Nick Kitchin Nick attended medical school in London where he obtained a BSc in Biochemistry with first class honours in 1988 before qualifying as a physician in 1991. His early clinical career was as an anaesthetist, probably the specialty in medicine where the clinical pharmacology of drugs can be most obviously observed. Seeking new challenges, Nick joined the pharmaceutical industry in 1994, initially working on the first clinical trials of new drugs in man – so-called Phase I trials. In 1995 he joined the Clinical Development department of Bayer Pharmaceuticals in the UK, working primarily on later stage (Phases II to IV) clinical trials of cardiovascular drugs, for example for the treatment of hypertension and hyperlipidaemia. In addition, Nick was the European project leader for a replacement treatment for patients with alpha-1 antitrypsin deficiency. Nick started specialising in the field of vaccines in 1998 when he joined Pasteur Mérieux MSD in the UK as Head of Clinical Affairs and Pharmacovigilance. He was integral to the licensure of, and subsequent national recommendation for, the company’s paediatric vaccines Pediacel®, Repevax®, and Revaxis®. Nick was also closely involved in the company’s response to the disproved allegations that MMR vaccine caused autism and bowel problems. After a spell as Medical Director for Baxter BioScience in the UK, Nick became Medical Director of Sanofi Pasteur MSD in the UK in 2004 where he was responsible for all activities of the medical department including Medical Affairs, Medical Information, Pharmacovigilance, Regulatory Affairs and Quality Assurance. Latterly he also took on responsibility for the company’s Health Economics and Market Access functions. In 2011 Nick joined Pfizer as a Senior Director in Vaccine Clinical Research where he is part of the global team working on the development of rLP2086, the company’s investigational vaccine against serogroup B meningococcal disease.

PROFESSOR MICHAEL LEVIN
ST MARY'S HOSPITAL, IMPERIAL COLLEGE LONDON

Michael Levin Michael Levin is Professor of Paediatrics and International Child Health, and Director of the Wellcome Centre for Tropical Clinical Medicine at Imperial College London. He trained in medicine in South Africa and in paediatrics in the UK before specialising in infectious diseases. His research has focused on life threatening infections of childhood. He currently heads an international EU-funded consortium studying novel diagnostic methods for tuberculosis in Africa working with colleagues in Malawi and South Africa. He recently led an ESPID funded consortium studying the genetic basis of meningococcal disease, and is a co-investigator on the MRC funded Phase III trial of fluids as supportive treatment for critical illness in African children (‘FEAST’), the results of which are recently published in the New England Journal of Medicine. He is the co-ordinator of a recently funded European Commission FP7 award studying the genetic basis of meningococcal and other life threatening bacterial infections of childhood, working with a consortium of colleagues from Europe, Africa and Singapore.

DR MARY RAMSAY
HPA COLINDALE, LONDON

Dr Mary Ramsay Dr Mary Ramsay obtained her medical degree at University College in London. Before joining the Health Protection Agency she held an academic post at St Mary’s Hospital Medical School in London. She became a Consultant Epidemiologist in 1994 with responsibility for the national surveillance of vaccine preventable diseases, blood-borne hepatitis and transfusion transmissible infections.

She regularly produces information to the Joint Committee on Vaccination and Immunisation to inform policy on vaccination and for a range of groups on the prevention and control of hepatitis. She is joint Chief Editor of Immunisation Against Infectious Diseases – the recognised national source of advice on vaccination, last published in 2006 and with subsequent updated chapters. She has also been involved in several national guidance documents on public health policy in her disease areas. In addition she provides expert clinical and public health advice in the field of vaccination and blood borne virus prevention. Her work has directly contributed to several major decisions on national vaccination policy, that, in turn has provided benefits for public health.

She often acts as a temporary advisor to WHO on vaccine preventable diseases and advises the European Centre for Disease Control on surveillance and epidemiology of vaccine preventable diseases.

Over the past two years she has been Head of the Immunisation, Hepatitis and Blood Safety Department. In this role she has continued to lead national surveillance and to demonstrate a track record in surveillance development, in managing acute investigations and in providing expert advice and support to a wide range of professionals and organisations who contribute to public health, both in England and overseas. Dr Ramsay’s research interests involve establishing the potential role for new vaccines.

DR CHRIS WORTH
UK MEDICAL DIRECTOR, NOVARTIS VACCINES


Chris Worth Dr Chris Worth MRCGP FFPM FFPH is UK and Northern Europe Medical Director for Novartis Vaccines and is based at the Frimley (UK) office. He graduated in medicine from Nottingham University Medical School. After working for some years in general practice in the Midlands, Chris became a successful Director of Public Health for a number of Health Authorities in West Yorkshire within the NHS during the 1990s. Chris was also Visiting Professor of Public Health at the University of Huddersfield during that period. He actively contributed to UK and local public health policy and wrote many scientific publications. Chris joined Janssen-Cilag Ltd in 2000 as Head of Medical Affairs, before moving to GSK as the UK Head of Vaccines in 2005. He has been with Novartis Vaccines since May 2007. Chris' current role is to lead a wide range of medical affairs activities in the UK, Ireland and Northern Europe across the whole vaccines portfolio, with special reference to meningococcal disease. In recent years, Chris has been Deputy Registrar of the Faculty of Pharmaceutical Medicine.


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