Meningitis Septicaemia Conference

8/3/2019 Meningitis Septicaemia Conference

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Meningitis and septicaemia inchildren and adults 2011

Tuesday 8 and Wednesday 9 November 2011

Royal Society of Medicine, London, UK

Organised by Meningitis Research Foundation

12 CPD Credits (event 66478)

Main sponsors

Also supported by


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5M E N I N G I T I S A N D S E P T I C A E M I A I N C H I L D R E N A N D A D U L T S 8 & 9 N O V E M B E R 2 0 1 1M E N I N G I T I S A N D S E P T I C A E M I A I N C H I L D R E N A N D A D U L T S 8 & 9 N O V E M B E R 2 0 1 1

Programme andOral Presentations

Meningitis and Septicaemiain Children and Adults

Tuesday 8 and Wednesday 9 November 2011

Useful information

eriesase contact a member of Meningitis Research Foundationsference team (identifiable by red badges) if you require anystance during the conference.

D certification

ase enlist for your certificate of attendance at registration.tificates will be available for collection from the registrationk at the end of the conference. For those delegates who arey attending Day One, your certificate will be available at theof the day.

bile phones/pagers

ase switch off all mobile phones and pagers when you are inlecture theatre.

estions during the conferenceestions will be taken at the discretion of the chairman. Waitl questions are invited and, if you would like to speak, raiser hand and wait to be called. When you are called, speakrly into the microphone handset, giving your name and

ere you are from. The handset should be held like a mobilene and the blue button pressed and held continuously whilespeak.

nference evaluationsase complete the conference evaluation form and hand it inhe registration desk before you leave. The form is included inr delegate pack.

nch and refreshments

ch and refreshments will be served in the Atrium and theR.

ne reception

wine reception will take place in the Atrium and the EDRr the Pfizer satellite session finishes on Day 1.

ster presentations

ase visit the posters during registration, morning andrnoon breaks, lunchtimes and the wine reception. Posters are

played around the Atrium walls and in the EDR. Authors ofters will be on hand to discuss their work and can bentified by their green badges. The award for the best posterbe presented after lunch on Day Two so that delegates can

w the winning poster during the final tea break thatrnoon.

e exhibition

exhibition will be open for viewing during registration,rning and afternoon coffee, lunch on both days and during

wine reception on Day One. The exhibition standsdisplayed around the Atrium and in the EDR.

Bulletin BoardIf you would like to leave a message for a delegate or participant,there is a message board on MRFs exhibition stand in theAtrium.

Business services

Basic business services, including photocopying (small charge percopy) and fax facilities (free of charge) are available in the EventsOffice on the lower ground floor.

Telephones

A public telephone is located in the cloakroom on theground floor.

Toilets

Toilets are situated downstairs through the Atrium and also bythe RSM restaurant on the ground floor.

Cloakroom facilities

The cloakroom is on the Ground Floor next to the mainreception. Lockers take 1 coins, which are returnable.

ParkingThere are no parking facilities available at One Wimpole Streetto accommodate vehicles. There are limited street parking spacesavailable in the surrounding area, as well as numerous parkingstructures close by, including one in Cavendish Square, directlyopposite the Society.

Disabled facilities and accessAll floors are accessible (except the fifth) via two lifts. The lecturetheatre is fully accessible and there are removable seats allowingspace for wheelchairs.

There is a personal delegate hearing system where each delegatewears an RSM receiver and earpiece.

There are accessible toilets on the first mezzanine floor of theLibrary and on the ground floor.

SmokingPlease note that smoking is not permitted in any part ofthe building.

Fire and evacuation procedureIf the fire alarm sounds:

Proceed quickly and calmly to the nearest fire exit. Escape routesand emergency exits are clearly indicated by Fire Exit signs. Donot stop to collect personal possessions.

Use the stairs do not use lifts.

Proceed to the assembly point in front of RSM in Henrietta Place.

First aid

There is a first aid room and many first aiders in the building. Ifan accident occurs, please contact reception on the ground floor.


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Treatment of meningitis and septicaemia, prevention of meningococcal disease

8:00 REGISTRATION AND COFFEE

8:20 NOVARTIS SATELLITE BREAKFAST SESSION

Tackling Meningitis in AfricaChair: Prof Robert Heyderman, Malawi-Liverpool-Wellcome Trust

9:20 Introduction of meningococcal serogroup A vaccine in the African meningitis beltDr Marc LaForce, Meningitis Vaccine Project, PATH/WHO, Ferney-Voltaire, France

9:50 Carriage and spread of meningococcus in the meningitis belt: the MenAfriCar projectDr Caroline Trotter, University of Bristol

10:20 Bill & Melinda Gates Foundation activity to combat meningitis in AfricaProf Richard Adegbola, Bill & Melinda Gates Foundation

10:50 COFFEE, EXHIBITION AND POSTERS

Current Issues in recognition and treatmentChair: Dr Simon Nadel, St Marys Hospital, Imperial College London

11:20 Pitfalls in recognition of meningitis and septicaemia in teenagers

Dr Nelly Ninis,St Marys Hospital, Imperial College London

11:50 Overview of evidence for managing children with sepsis, including fluidmanagement of children in shockDr Mark Peters, Institute of Child Health, University College London

12:20 Current advances in sepsis management in adultsProf Mervyn Singer, University College London

12:50 LUNCH, EXHIBITION AND POSTERS

13:50 AWARD FOR THE BEST POSTER

Prevention of meningococcal diseaseChair: Prof Ray Borrow, Vaccine Evaluation Unit, Health Protection Agency, Manchester

14:00 Changes to UK immunisation programme, including prospects for ateenage meningococcal boosterProf Andrew Pollard, University of Oxford

14:25 Dealing with a localised MenB epidemic the Cumbrian situationDr Paul Cleary, HPA Northwest, Liverpool

14:50 COFFEE, EXHIBITION AND POSTERS

Prospects for prevention of meningococcal B diseaseChair: Prof Ian Feavers, National Institute for Biological Standards and Control

15:10 Prospects for use of Novartis 4CMenB vaccine

Dr Peter Dull, Novartis Vaccines and Diagnostics, Cambridge, MA, USA

15:40 Pfizer strategy for prevention of meningococcal B diseaseDr Kathrin U Jansen, Pfizer Inc, NY, USA

16:10 Interactive session: Implementing a MenB vaccineProf Andrew Pollard, University of Oxford moderator

1 6:50 CL OS E

rden of meningitis, advances from research, prevention of pneumococcal disease

0 REGISTRATION AND COFFEE

5 Welcome Chris Head, CEO, Meningitis Research Foundation, UK

unting the cost of meningitis and septicaemia: burden of illnessair: Prof George Griffin, St Georges University of London

5 Patient experience of pneumococcal diseaseScottie Kern, Member of Meningitis Reasearch Foundation

0 Current epidemiology of meningococcal disease in the UK and Europe, including issues forsurveillance relating to a MenB vaccineDr Mary Ramsay, HPA Colindale, London

10 Neurological impact of meningitisDr Peta Sharples, University of Bristol

40 Counting the cost of meningitisClaire Wright, Meningitis Research Foundation

50 COFFEE, EXHIBITION AND POSTERS

st of illness, cost effectiveness analysis and decisions about introducing vaccinesair: Dr Mary Ramsay

20 Modelling the potential impact of meningococcal B vaccines in EnglandDr Hannah Christensen, University of Bristol

50 Meningococcal outcomes study in adolescents and in childrenProf Russell Viner, Institute of Child Health, University of London

20 Any questions: Meningococcal vaccines and objective policy and purchasing decisionsProf Adam Finn, University of Bristol moderator

00 LUNCH, EXHIBITION AND POSTERS

vances from research: implications for prevention and treatmentair: Prof Christoph Tang, University of Oxford

00 Reducing the very high mortality for adult meningitis in AfricaProf Robert Heyderman,Malawi-Liverpool-Wellcome Trust

30 Genetic susceptibility to meningococcal disease the role of FactorH and Factor H-related proteinsProf Michael Levin, St Marys Hospital, Imperial College London

00 Bacterial meningitis in infants: the burden of disease and prospects for improving the outcomeProf Paul Heath,St Georges University of London

30 COFFEE, EXHIBITION AND POSTERS

venting pneumococcal diseaseair: Prof David Goldblatt, Institute of Child Health, University College London

00 Impact of pneumococcal conjugate vaccination in EnglandPauline Kaye, HPA Centre for Infections, London

30 Need for and development of protein-based pneumococcal vaccineDr William Hausdorff, GlaxoSmithKline Biologicals, Wavre, Belgium

00 PFIZER SATELLITE SESSION

00 WINE RECEPTION, EXHIBITION AND POSTERS

M E N I N G I T I S A N D S E P T I C A E M I A I N C H I L D R E N A N D A D U L T S T U E S D A Y 8 N O V E M B E R 2 0 1 1 M E N I N G I T I S A N D S E P T I C A E M I A I N C H I L D R E N A N D A D U L T S W E D N E S D A Y 9 N O V E M B E R 2 0 1 1 7

Programme Wednesday 9 November 2011Programme Tuesday 8 November 2011


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Morning Tuesday 8 November 2011Morning Tuesday 8 November 2011

Notes

15 Welcome Christopher Head, CEO, Meningitis Research Foundation, UK

Abstract

Following the introduction of conjugate vaccination against serogroup C meningococcal disease in the UK, the number ofcases of invasive meningococcal disease (IMD) due to serogroup C infection declined from 955 in 1998/9 to 13 in 2008/9.Cases due to serogroup B have also declined, but less dramatically, from 1401 to 786 over the same period. Despite thisdecline, the overall incidence of IMD in the UK remains high in comparison to other European countries. In 2009, the latestyear for which Europe-wide data are available, 29 countries reported 4,637 cases of IMD, with an overall incidence ofIMD of 0.92 per 100,000 population; the highest rates were reported from the Republic of Ireland (3.4/100,000) and theUK (2.0/100,000). Between 2006/7 and 2009/10 serogroup B (MenB) accounted for 88% (3,907/4,435) of cases inEngland and Wales. The highest incidence of MenB was observed among infants (38.2/100,000) and cases in those aged


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Claires responsibilities at MRF include maintaining and developing a range of informationresources for the public and health professionals. These include paper and electronicpublications for health professionals and the public, presentation materials, fact sheets,statistics, articles for medical/nursing media, and web based information. She also liaises withhealth professionals on behalf of MRF members who wish to ask specific health relatedquestions.

Claire has a biology background and has spent much of the past year undertaking a projectwhich aims to count the lifelong costs of a severe case of meningitis and septicaemia.

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Claire Wright

Cost of illness, cost effectiveness analysis anddecisions about introducing vaccines

Dr Mary Ramsay, HPA Colindale, London

Biography on page 8

Chair:

COFFEE, EXHIBITION AND POSTERS10:50

Claire Wright, Medical Information Officer, Meningitis ResearchFoundation, UKCounting the cost of meningitis

Notes

Notes

Hannah Christensen is an epidemiologist with particular interests in infectious diseases,modelling and health economics. Having previously worked for the Health Protection AgencySouth West Regional Epidemiology Unit and the South West Public Health Observatory shehas recently completed her PhD at the University of Bristol. Her thesis used infectious diseaseand economic models to predict the potential impact of introducing a new meningococcalvaccine into the UK schedule. Hannah is currently working at the University of Bristol on theTARGET study, an NIHR-funded Programme Grant aiming t o improve the quality of care givento children presenting to primary care with respiratory tract infections (RTIs). Her researchfocuses on assessing the population impact of public health interventions aiming to reducelevels of infectious disease.

11:20

Dr Hannah Christensen

Dr Hannah Christensen, University of BristolModelling the potential impact of meningococcal B vaccines in England

AbstractLong-term sequelae resulting from meningococcal disease (MD) impose a considerable burden on healthcareresources, however there is a lack of published information in the UK on costs associated with severe cases.

Economic evaluations such as cost effectiveness analyses (CEA) are becoming an increasingly important feature indecisions about whether immunisation programmes should be implemented. The conclusions reached by theseanalyses are dependent on the accuracy of the input data.

AIM: To estimate lifelong rehabilitation costs associated with severe cases of MD and to present these costs in aformat appropriate for use in a cost effectiveness analysis so that in future data input into such models can moreaccurately represent costs associated with severe outcome of MD.

METHODS: Two severe scenarios of MD with major sequelae were developed; one which presented acutely asmeningitis and the other as septicaemia. They were based on systematic reviews of literature describing the sequelaeof MD, dialogue with MRF members who have experience of MD and discussions with paediatricians who have beenresponsible for managing children with MD over many years. The two scenarios were devised to represent casestypical of the severe end of the spectrum.

To obtain a comprehensive list of the health, educational and other resources used by survivors during and since theiracute illness, families of individuals with sequelae similar to those in each of our scenarios were interviewed. Relevantacademics and professionals in health, social care and education were consulted in order to ensure that our scenariosaccurately represented the treatment and support that individuals with such sequelae might realistically receive fromthe NHS, the local authority and personal social services (PSS).

The majority of costs were derived from English Department of Health reference costs and unit costs of health andsocial care reflecting values for the financial year 2008-9. Costs were based on a life expectancy of 70 years in eachscenario and are presented at a discount rate of 3.5% for the first 30 years and 3% thereafter as recommended bythe UK treasury (non-discounted costs are also presented for comparison). Costs are presented from both anNHS/PSS perspective and a government perspective.

RESULTS: This study has revealed that severe cases of disease which result in longterm sequelae can result in costs tothe NHS/PSS of around 150,000-190,000 in the first year alone. Over a lifetime of 70 years, discounted costsfrom an NHS/PSS perspective ranged from approximately 600,000 to 1,000,000 (1,230,000 to 3,160,000undiscounted) and discounted costs from a government perspective ranged from 1,300,000 to 1,700,000(2,980,000 to 4,280,000 undiscounted).

CONCLUSION: This study fills a gap in UK literature and can potentially be input into CEA to better represent thecost of illness at the severe end of the spectrum. Costs from a government perspective highlight the wider impactsof this disease which is important f or clinical decision makers, budgetary and service planners to be aware of whenmaking decisions about the benefits of implementing health policy.

Notes

Abstract

Despite new antimicrobial agents and vaccine advances, bacterial meningitis remains an important cause of deathand acquired disability in childhood. Half of all cases of non-traumatic encephalopathy admitted to the South WestRegional PICU over a five year period were due to CNS infection. Improvements in paediatric intensive care have ledto a fall in mortality rates from meningitis, leading to increased focus on quality of outcome in survivors. Variousstudies have suggested that, overall, 10-20% of survivors of meningitis are left with neurological disability. Data fromBristol suggests outcome in children with meningitis admitted to PICU is poor in 26% and that a further 15% havemoderate or mild disability.

Brain damage in meningitis results from activation of host inflammatory pathways, mediated by cytokines. Cytokineproduction activates a cascade of destructive molecular events, including generation of excitatory amino acids,generation of nitrous oxide and free radicals, and calcium influx into neurons. These processes result in cellular energydepletion, loss of cell membrane integrity, entry of fluid into cells, cellular lysis and neuronal death by necrosis.Inflammatory processes, including glutamate production, may also result in activation of enzymes responsible forprogrammed cell death, leading to apoptotic neuronal loss.

In experimental models of meningitis, cerebral blood flow increases in the first 1-6 hours after infection and isassociated with raised intracranial pressure and brain oedema formation. As infection progresses, cerebral blood flowdecreases in associated with increasing intracranial pressure. Cerebral oxygen delivery becomes inadequate to meetthe brains metabolic needs, leading to ischaemic brain damage.

Inflammatory processes can also cause raised intracranial pressure by blocking normal drainage pathways forcerebrospinal fluid, causing ventriculomegaly with raised intracranial pressure (hydrocephalus). Bacterial meningitis isthe single largest cause of non-tumoural hydrocephalus. Single hospital series suggest hydrocephalus complicates1/7-2.8% of episodes of bacterial meningitis in children.

The impact in any individual patient of an acquired brain injury such as meningitis, depends on the areas of the braininvolved. Damage to the frontal lobes causes difficulties with attention, intellect, executive function and the inhibitoryaspects of behaviour, and higher aspects of memory function, including working memory. Temporal lobe damage, forexample, by uncal herniation, causes problems with fundamental memory functions s uch as encoding and retrieval,as well as language dysfunction and behavioural and emotional difficulties. Parietal lobe damage can cause problemswith language and visuo-spatial functioning.

Occipital lobe damage can cause visual problems, such as cortical blindness or visual field defects. Raised intracranialpressure can result in brain stem dysfunction, leading to problems with arousal or attention, cranial nerve palsies andmotor dysfunction (spastic quadriparesis or ataxia).

There is increasing recognition that neuronal plasticity does not necessarily result in children doing better than adultsfollowing acquired brain damage. Young children, in particular, may do worse. Early intensive neurorehabilitation isindicated in cases with significant disability, to optimise recovery. Cognitive and behavioural difficulties may notbecome apparent until some years after the acute illness, emphasising the need for long term monitoring, includingof milder cases.


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Professor Adam Finn is Head of t he Academic Unit of Child Health at Bristol Medical School,School of Clinical Sciences and an honorary consultant in paediatric infectious diseases andimmunology at Bristol Royal Hospital for Children. He is director of the South West Medicinesfor Children Research Network and heads the Bristol Children's Vaccine Centre. He trained inInfectious Diseases at the Children's Hospital of Philadelphia and in Immunology at theInstitute 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 ofmeningococcal group C and other vaccines. His current main research interest is the mucosal

immune response to respiratory bacteria including pneumococcus and meningococcus.

Any questions: Meningococcal vaccines and objective policy andpurchasing decisions

Topical discussion in which a panel of experts from the worlds ofepidemiology, cost-benefit analysis, public health policy and vaccineproduction are posed questions by the audience

Moderator: Professor Adam Finn, University of Bristol

Notes

Prof Adam Finn

12:20

Panel:

Notes

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

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

Dr Dulls research areas have included meningococcal meningitis outbreak investigations andvaccination implementation strategies in the United States and Africa, oropharyngeal carriageof Neisseria meningitidis associated with the Hajj, and molecular diagnostics of bacterialmeningitis.

Dr Peter Dull, Novartis Vaccines and Diagnostics, Cambridge, MA,USA

Dr Peter Dull

Prof. John Edmunds' research concentrates on the design of cost-effective interventionprogrammes against infectious diseases. He has a Chair in Modelling Infectious Diseases at theLondon School of Hygiene and Tropical Medicine. Before that he was the head of theModelling and Economics Unit at the Health Protection Agency. He has co-authored over 100peer-review articles, and acted as an advisor on national and international committees onmany occasions on topics ranging from HPV vaccination to pandemic influenza. He has beena member of the WHO HPV Expert Advisory Group, and is now a member of the committeethat advises WHO on modelling and economic evaluation for vaccination programmes(QUIVER).

Professor John Edmunds, London School of Hygiene and TropicalMedicine, UK

Prof John Edmunds

Abstract

The MOSAIC study was a nationally representative case-control study of the outcomes and costs associated withsurviving invasive meningococcal serogroup B disease (MenB). It was commissioned by the Meningitis Trust to informcost-effectiveness decisions regarding MenB vaccines and to improve aftercare for survivors.

Survivors (cases) 3-16y were identified through a national database and healthy controls via case GPs. Consentingsubjects underwent a standardised assessment. We recruited 573 subjects (245 cases and 328 controls), of whom 221were well-matched case-control pairs.

We found that MenB disease is associated with a marked series of deficits in survivors, including reduced quality oflife, psychological disorders, IQ and memory impairment as well as hearing loss, limb amputations and scarring.Economic analyses showed significantly increased medical and social costs and significant QALY loss in cases comparedwith controls.

This is the largest outcome study of MenB disease in children and adolescents. Economic evaluation of these deficitswill inform vaccine development and implementation decisions and improved aftercare for survivors.

Russell Viner is an academic paediatrician and Professor of Adolescent Health at the UCLInstitute of Child Health in London. He has a major interest in follow-up studies, and hascollaborated with paediatric infectious diseases colleagues to undertake a series of follow-upstudies of invasive meningococcal and pneumococcal disease in children and adolescents,funded by Meningitis Research Foundation. Most recently he was commissioned by theMeningitis Trust to undertake the MOSAIC study (Meningococcal outcome study inadolescents and in children), the largest study to date of the outcomes of serogroup Bmeningococcal disease.

Professor Russell Viner, Institute of Child Health,University College LondonMeningococcal outcomes study in adolescents and in children

Prof Russell Viner

:50

Abstract

Neisseria meningitidis remains an important cause of meningitis and septicaemia. The difficulty faced by both thepublic and clinicians is that the early signs and symptoms of meningococcal disease can be non-specific; howeverinvasive disease can progress rapidly and be fatal within hours. The key to preventing disease, therefore, isvaccination. Serogroup B (MenB) is responsible for most meningococcal disease in the UK. There is currently nobroadly effective vaccine against this group, but new MenB vaccines are expected to go to licensure shortly. Ourobjective was to assess (using mathematical models) the potential epidemiological and economic impact of introducinga meningococcal vaccine, able to protect against MenB disease, into the vaccination schedule for England.

Two types of model, one allowing for direct protection only (cohort model) and another also allowing for herdimmunity effects (transmission dynamic model) were developed following hypothetical birth cohorts over their lifetime(max 100 years). A number of contemporary data sources were used to estimate the epidemiological parameters andthe costs of meningococcal disease and vaccination to the health service. Future costs and benefits were discountedback to 2008. Several routine and catch-up vaccination strategies were simulated.

In the current model, assuming the vaccine could provide direct protection only, predictions indicate that routine infantvaccination (vaccination at 2,3,4+12 months of age, 75% effective vaccine coverage, 36 months average protectionfollowing booster) could prevent 20% of meningococcal disease cases annually. However, this strategy may only becost effective if the vaccine were to cost 7 per dose. Catch-up campaigns (17 years) are unlikely to be cost-effectiveif the vaccine does not affect carriage. If the vaccine does have a reasonable (60%) effect on reducing carriage, the

annual number of cases could be reduced by 71% after 10 years by introducing routine infant immunisation plus acatch-up campaign. These results are sensitive to assumptions about: disease incidence and case fatality; sequelaerates; the profile of the vaccine; carriage prevalence; population mixing patterns; and discount rates.

Introducing a new meningococcal vaccine, with the capacity to protect against MenB could reduce disease levels, withsubstantial reductions predicted when the vaccine can prevent carriage as well as disease. Such a vaccinationprogramme could be cost-effective if the vaccine were to be competitively priced.


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Afternoon Tuesday 8 November 2011Afternoon Tuesday 8 November 2011

Professor Christoph Tang, University of Oxford

Professor Christoph Tang is currently Professor of Cellular Pathology at the Sir William DunnSchool of Pathology at the University of Oxford, having recently moved from the Centre forMolecular Microbiology and Infection at Imperial College London. His group studies thepathogenesis and prevention of disease caused by Neisseria meningitidis andShigella flexneri,particularly during interactions with the host innate immune system. He was previously anMRC Clinician Scientist at the University of Oxford, and completed his PhD at the RoyalPostgraduate Medical School on the identification of virulence factors in the fungal pathogen,Aspergillus fumigates. Christoph originally trained in medicine at the University of Liverpooland spent two years working in The Gambia, West Africa.

Prof Christopher Tang

Advances from research: implications for

prevention and treatment

air:

Professor Robert Heyderman, Malawi-Liverpool-Wellcome TrustReducing the very high mortality for adult meningitis in Africa

14:00

Rob Heyderman is Professor of Tropical Medicine and Director of the Malawi-Liverpool-Wellcome Trust Clinical Research Programme. He trained in London and Zimbabwe. Hiscurrent research interests comprise the endothelial biology, coagulopathy and immunology ofsevere infection; the development of naturally acquired immunity to Neisseria meningitidisandStreptococcus pneumoniae; regulation of the host inflammatory response; and the clinicaldiagnosis and management of meningitis and septicaemia. Current initiatives include newapproaches to mucosal vaccination to prevent pneumonia and meningitis both in the UK andin the tropics; management of meningitis and severe sepsis in resource-poor settings; andmicrobial genetic diversity in the contact of HIV infection.

Abstract

Meningitis in adults is a common reason for hospital admission in sub-Saharan Africa and isassociated with an HIV seroprevelence exceeding 80%. The disease is also associated with an unacceptably high rateof death and disability. Studies conducted in Malawi, funded by MRF, have found no benefit from either adjunctive

corticosteroids or oral glycerol in these populations. The cause of this high mortality remains uncertain but latepresentation and delayed door-to-needle times, marked fluid, acid-base and electrolyte derangement on admission,impaired sterilisation of the cerebrospinal fluid (CSF), and viral co-infection of the central nervous system may allcontribute. The studies that have attempted to address these issues will be summarised.

Prof Robert Heyderman

Notes

Professor Michael Levin, St Marys Hospital, Imperial College LondonGenetic susceptibility to meningococcal disease the role of Factor Hand Factor H-related proteins

14:30

Michael Levin is Professor of Paediatrics and International Child Health, and Director of theWellcome Centre for Tropical Clinical Medicine at Imperial College London. He trained inmedicine 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 aninternational EU-funded consortium studying novel diagnostic methods for tuberculosis inAfrica working with colleagues in Malawi and South Africa. He recently led an ESPID fundedconsortium studying the genetic basis of meningococcal disease, and is a co-investigator onthe MRC funded Phase III trial of fluids as supportive treatment for critical illness in Africanchildren (FEAST), the results of which are recently published in the New England Journal ofMedicine. He is the co-ordinator of a recently funded European Commission FP7 awardstudying the genetic basis of meningococcal and other life threatening bacterial infections ofchildhood, working with a consortium of colleagues from Europe, Africa and Singapore.

Prof Michael Levin

AbstractThere is clear evidence that genetic factors are important determinants of meningococcal disease susceptibility andseverity, and have also been implicated in other forms of meningitis. A number of studies of genetic associations withmeningococcal disease have been published, but many of the reported genetic associations have not been validatedin subsequent studies. Numerous methodological flaws in early studies have made interpretation of the findingsdifficult. In order to conduct a definitive study of the genetic basis of meningococcal disease, an international studywas established, with support from ESPID and MRF. This study aimed to establish a large enough cohort of patientswith meningococcal disease and controls to allow Genome Wide study (GWAS) of over 500,000 genetic variants.

The combined cohort of patients from UK, Holland, Austria and Spain included over 1,500 cases. An Initial GWAS wasconducted in the UK cohort, with validation in the central and southern European cohorts. This study has definitivelyidentified genetic variation in the Factor H gene and FH related genes as controlling meningococcal diseasesusceptibility.

Further analysis of the cohorts to identify severity genes and those controlling outcome is underway, and thesignificance of the findings to date will be discussed in this talk.

Michael Levin on behalf of the International meningococcal disease consortium.

Notes

LUNCH, EXHIBITION AND POSTERS:00

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 MScand PhD from the London School of Hygiene and Tropical Medicine. Her research focuses onassessing the population impact of vaccination against meningococcal and pneumococcaldisease, using a range of research methods including mathematical modelling, cost-effectiveness studies, analyses of large databases and seroprevalence studies. She is currentlyworking on the MenAfriCar project (www.menafricar.org).

Dr Caroline Trotter, University of Bristol, UK

Dr Caroline Trotter

Dorian Kennedy is a career Civil Servant who worked in the Food Standards Agency on a rangeof food safety, quality and nutrition issues before joining the Department of Health in 2002 towork on Immunisation. He has been heavily involved in HPV and pneumococcal vaccinesbeing added to the routine immunisation programmes in the UK. In addition to immunisation,he was responsible for co-ordinating the pandemic flu preparedness work in the Departmentfrom 2004 2006. Since 2007, he has been Head of Immunisation Branch in the Departmentof Health.

Dr Dorian Kennedy, Department of Health, London, UK

Dr Dorian Kennedy

Professor Russell Viner, Institute of Child Health,University College LondonBiography on page 12


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Afternoon Tuesday 8 November 2011 Afternoon Tuesday 8 November 2011

David Goldblatt obtained his medical degree from the University of Cape Town, South Africa,his paediatric qualifications from the Royal College of Physicians (London) and a PhD inImmunology from the University of London, UK. He is currently Professor of Vaccinology andImmunology and Head of the Immunobiology Unit at the Institute of Child Health, UniversityCollege London (UCL) as well as a Consultant Paediatric Immunologist at the Great OrmondStreet Hospital for Children NHS Trust. He is the Director of Clinical R&D for the jointInstitution where he is also Director of the National Institute for Health Research (NIHR)Specialist Biomedical Research Centre. In 2009 he was appointed as Program Director of theChild Health theme for the UCL Partners Academic Health Science Centre.

He has a long-standing interest in the immune response to vaccines and infectious diseases inchildhood and has an active research programme studying natural and vaccine inducedimmunity to infectious diseases. He is a regular advisor to the World Health Organization(WHO) on vaccines and is Director of the WHO Reference Laboratory for Pneumococcal

Serology based at the UCL Institute of Child Health in London. He served as a member of the UK Department ofHealth Joint Committee on Vaccines and Immunisation (JCVI) for 10 years (1997-2007) and contuinues to contributeto UK policy via membership of JCVI subcommittees. He has been a member of the MRC Infection and ImmunityPanel, co-chaired the Wellcome Trust Immunology and Infectious Disease Funding Committee until its close in 2011and continues as a member of the Wellcome Trusts Immune System in Health and Disease Expert Review Group.

es

Prof David Goldblatt

Preventing pneumococcal disease

Professor David Goldblatt, Institute of Child Health, UniversityCollege London

Chair:

Pauline Kaye, HPA Centre for Infections, LondonImpact of pneumococcal conjugate vaccination in England

16:00

Abstract

Invasive pneumococcal disease (IPD) caused by Streptococcus pneumoniae is a leading cause of morbidity andmortality in children causing septicaemia, meningitis and pneumonia. In England and Wales, prior to the introductionof the pneumococcal conjugate vaccine (PCV) around 5,000-6,000 cases of (IPD) were reported annually bylaboratories to the Health Protection Agency (HPA). The highest incidence of IPD is found in children aged less thanone year and in adults aged over 65 years. Around 20 to 25% of children with IPD aged less than five years will havemeningitis of whom around 13% die.

Although around 90 different serotypes ofS.pnuemoniae exist, when the new seven-valent pneumococcal conjugatevaccine (PCV7) was introduced into the UK schedule in September 2006, it covered around 70% of the serotypesinfecting children under the age of five years. PCV13 replaced PCV7 in April 2010 and contained a further sixserotypes. Two of these (19A and 7F) had emerged as major causes of disease after the introduction of PCV7 as aresult of serotype replacement.

Since 1996, enhanced national surveillance by the HPA in England and Wales has provided a baseline against whichto evaluate the impact of PCV7 and PCV13 on vaccine t ype and non-vaccine type invasive pneumococcal disease invaccinated cohorts.

The clear impact of the vaccine on the incidence of IPD in different age groups is apparent when incidence rate ratiosare calculated using incidence rates from time periods before and after the introduction of the vaccine. Havingaccounted for changes in the sensitivity of the surveillance systems over time, these ratios show a 98% reduction ofPCV7 vaccine type IPD in children aged less than two years with lesser reductions occurring in older age groups dueto herd immunity. In children aged under five years with IPD and meningitis, a 95% reduction in disease caused byPCV7 serotypes has been estimated, although for both groups (with and without meningitis), these reductions arecountered by increases in incidence of disease caused by non PCV7 serotypes. However the overall reduction inmeningitis caused by all types of IPD in children aged less than five years has been estimated at around 44%.

Using HPA data it has been possible to estimate that around 500 IPD cases a year in children less than five years ofage and 25-30 deaths a year in the same age group have been prevented by the PCV7 programme.

The impact of the PCV programme on serotype distribution in England and Wales can be shown graphically by plottingthe total annual cumulative weekly number of isolates referred for serotyping. The reduction in cases after theintroduction of PCV7 can be clearly seen for vaccine type serotypes in graphs showing either all cases of IPD ormeningitis only cases.

Eighteen months after the replacement of PCV7 by PCV13, invasive disease and meningitis caused by the additionalsix serotypes in PCV13 is declining in PCV13 eligible age groups although the potential of further serotypereplacement occurring following the introduction of PCV13 needs careful monitoring.

Notes

es

After graduating from Edinburgh University in 1982, Pauline Kaye (Waight) worked as ascientist for 18 years in the Immunisation Department of the PHLS on a wide variety ofsurveillance activities for vaccine preventable diseases and HIV, research projects and Dept ofHealth sponsored clinical trials of vaccines including the Meningococcal C conjugate vaccinetrials prior to their introduction into the UK vaccination schedule. She left Britain in 2001 towork for the Medical Research Council in The Gambia where she continued to be involved inclinical trial work, this time for new malaria vaccines, on long term hepatitis B vaccinationsurveillance, research and surveillance work involving congenital CMV infection, and on HIVsurveillance in Guinea Bissau. She returned to the UK in 2005 to the HPA which had nowreplaced the PHLS to work in the Department of Health Care Associated Infections andAntimicrobial Resistance for 18 months before returning to Immunisation to help implementand manage the enhanced surveillance system for invasive pneumococcal disease followingthe introduction of PCV7 in the UK. She also continues to work on the clinical trials which

continue within the Immunisation Department as part of the National Vaccine Evaluation Consortium. As with many

other HPA staff she was heavily involved in the HPA response to swine f lu in 2009.

Pauline Kaye

Paul Heath is a Professor/Honorary Consultant in Paediatric Infectious Diseases at St Georges,University of London and Vaccine Institute in London. His training in paediatrics and infectiousdiseases was at the Royal Childrens Hospital, Melbourne, the John Radcliffe Hospital, Oxfordand St Georges Hospital, London. His particular research interests are in the epidemiology ofvaccine preventable diseases, in clinical vaccine trials, particularly in at-risk groups, and inperinatal infections. He coordinates a national neonatal infection surveillance network(neonIN) and currently a national study on neonatal meningitis. He sits on national committeesconcerned with meningitis, Group B streptococcus prevention, pneumococcal and Hibinfections, neonatal infections and on immunisation policies in children. He is a Fellow of theRoyal Australasian College of Physicians, a Fellow of the Royal College of Paediatrics and ChildHealth, a member of the committee for Scientific Affairs and Awards of the European Societyof Paediatric Infectious Diseases and a member of the steering committee of the internationalBrighton Collaboration on vaccine safety.

Abstract

The outcome of neonatal meningitis remains unacceptable. Despite declines in mortality over the last 2 decades, themost recent data on neurodevelopmental outcome suggest little change with up to 50% of infants having some formof disability at 5 years of age. Strategies for prevention are relatively few but should be prioritised and vaccination,especially with an effective Group B Streptococcal vaccine holds much promise. Using recent developments in themanagement of meningococcal disease as a model, it seems likely that a number of aspects of the currentmanagement of neonatal meningitis could be improved with potential for better outcomes. These might include earlierrecognition of signs and symptoms by parents and healthcare workers, earlier identification of the causative pathogen,earlier initiation of antimicrobial therapy, improvements in supportive care, better antimicrobial agents and effectiveadjunctive therapies. More data are needed to quantify these issues, formulate new strategies of intervention andultimately demonstrate their efficacy.

Professor Paul Heath, St Georges University of LondonBacterial meningitis in infants: the burden of disease and prospectsfor improving the outcome

5:00

s

Prof Paul Heath



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Afternoon Tuesday 8 November 2011 Afternoon Tuesday 8 November 2011

Dr John Porter trained in Oxford and Newcastle medical schools, qualifying in 1995 beforespecialising in paediatrics. He then further specialised in paediatric diabetes and endocrinologyat Birmingham Childrens Hospital. Dr Porters PhD was in the genetics of childhood diabetes.He joined Pfizer from the NHS in 2008, and was appointed as a medical team leader for Pfizer in2009. His current role is as medical team lead managing the medical teams responsible forPfizers anti-infectives, vaccines and endocrinology portfolios. He continues to practice clinicalmedicine with regular clinics in paediatrics.

Dr John Porter

Notes

Dr John Porter BA (Hons) MBBS PhDChair:

Dr Laura York, Senior Director, International Scientific & ClinicalAffairs, Pfizer Vaccines

Speaker:

Dr York is Senior Director of International Scientific & Clinical Affairs, Pfizer Vaccines, and iscurrently based in Paris, France. She has worked in the vaccine field for over 20 years, gainingextensive experience in all phases of vaccine development. She first led a research groupevaluating early vaccine candidates and novel adjuvants. Transitioning to Scientific Affairs in1999, she focuses on licensure of late stage candidates and inclusion of newly licensed vaccines,such as Prevenar 13, into national immunization programs. Dr York did her post-graduate trainingin Canada, receiving her PhD (Microbiology) from the University of Saskatchewan aftercompleting a MSc (Immunology) at Memorial University.

Abstract

Pfizer Vaccines has a strong heritage in conjugate vaccines for the prevention of bacterialinfections, including meningitis, developing HiBtiter, Meningitec, and Prevenar/Prevenar 13 for

the prevention of Haemophilus influenzae type B, meningococcal serogroup C and pneumococcal infections,respectively. Though it was well known that antibodies directed to the polysaccharide capsule surro unding these bacteriawere protective, vaccines made of purified polysaccharide were unable to generate protective responses in youngchildren. This limitation was finally addressed by conjugation, the chemical linking of the polysaccharide to a proteincarrier, and the implementation of conjugate vaccines has led to significant reductions in Hib, meningococcal C andpneumococcal infections. The rationale for the development of Prevenar, and subsequently Prevenar 13, was prevention

of pneumococcal disease through the use of effective vaccines. Prevenar was licensed at the beginning of the centuryand has been used globally in national immunisation programs. Prevenar has been seen to be highly effective inpreventing pneumococcal disease, including pneumonia, in vaccinated children, and in providing protection indirectly byreducing nasopharyngeal carriage in vaccinees and subsequent transmission to unvaccinated individuals. Prevenar 13,licensed since 2009, was developed to provide the broadest global coverage with the inclusion of six additionalpneumococcal serotypes . Prevenar 13 is licensed in >80 countries around the world and is included in the nationalimmunisation programmes of 28 countries. With the transition to PCV13, IPD due to the six additional serotypes hasbeen shown to have declined while the significant impact on IPD due to the original Prevenar types remainsunchanged. Pneumococcal serotypes seen in pediatric disease also cause disease in adults. The clinical developmentprogramme and recent licensure of Prevenar 13 for use in adults aged 50 years and above has now offered the potentialbenefits of conjugate vaccine technology towards addressing the burden of pneumococcal disease in adults. The clinicalstudies performed in adults for the licensure of Prevenar 13 involved over 6000 subjects providing robust safety andimmunogenicity data. The data demonstrated that Prevenar 13 is immunogenic, as demonstrated by the induction ofopsonophagocytic (killing) antibody, in individuals nave to pneumococcal vaccine as well as in those who have beenpreviously immunized with a plain polysaccharide vaccine. Data from longer term studies have also illustrated the abilityto re-vaccinate healthy individuals who had received one dose of Prevenar 13 previously. Considerations on preventionof pneumococcal disease in adults should now include the potential use of Prevenar 13.

Dr Laura York

Notes

AbstractPneumococcal polysaccharide conjugate vaccines (PCV) have proven to be extremely effective in preventing invasivediseaase (IPD), both in the infant target population and in older, unvaccinated age groups through herd protection.Nonetheless, with more than 40 antigenically distinct serogroups (comprising more than 90 serotypes) ofpneumococcus, it was expected that the overall effectiveness of these vaccines against IPD in children would be limitedto prevention of the 80-90% of IPD caused by the 10-11 serogroups represented in current vaccine formulations. Inaddition, it has been well documented that following introduction of the heptavalent PCV there has been nearcomplete replacement of the vaccine serotypes colonizing the nasopharynx with non-vaccine types. Therefore, somereplacement disease was also anticipated and this has been borne out by post-marketing surveillance. Considering thedynamics of pneumococcal serotype epidemiology, multi-factorial in origin, large uncertainty exists as to whatproportion of this IPD increase is actually attributable to heptavalent PCV use, whether replacement in IPD also erodesvaccine effectiveness against other disease manifestations such as pneumonia and acute otitis media, and howserotype and disease epidemiology may evolve in the future.

There has long been interest in a protein-based vaccine that could provide broad protection against all pneumococci.The ideal candidate would be expressed by all strains regardless of serotype, be antigenically highly conserved, andrepresent a virulence or growth factor. Unfortunately, many potential candidates fail in one or more of these areas.In addition, to enhance t he likelihood of effective protection and avoiding immune evasion, multiple antigens may bedesirable. An important hurdle to development has been the absence, to date, of a clinical demonstration in humansthat such protein-based vaccines can indeed prevent disease. Vaccine developers have been reluctant to make majorinvestments in the needed studies without recognized immune correlates of clinical protection against IPD or wellvalidated pre-clinical disease models. In addition, clinical study design is complicated by the widespreadimplementation of highly effective multivalent conjugate vaccines.

There are a number of interesting protein candidates currently being explored, including choline binding protein A(CbpA), pneumococcal surface protein A (PspA), pneumococcal surface adhesion A (PsaA), detoxified pneumolysin(dPly) and pneumococcal histidine triad (Pht) proteins. Regarding the latter two, pneumolysin is produced by virtuallyall pneumococcal strains and is an important virulence factor, exerting cytotoxic effects on epithelial cells through its

membrane pore-forming activity. Four members of the Pht protein family have been described, and found to be wellconserved across the pneumococcal species. Recent data suggest that Pht proteins are involved in the regulation of Znor Mn homeostasis, which are important for the growth of the bacteria. Immunisation with Pht, in particular PhtD, hasbeen shown to elicit protection against severalS. pneumoniae serotypes in various mouse models. Immunisation witha combined dPly and PhtD formulation was shown to protect monkeys from pneumococcal pneumonia. Overall,results indicate dPly and PhtD are promising candidates for development of a protein based pneumococcal vaccine.

Preventing pneumococcal disease:Where have we come from and what does the future hold?

17:00 PFIZER SATELLITE SESSIONDr William Hausdorff, GlaxoSmithKline Biologicals, Wavre, BelgiumNeed for and development of protein-based pneumococcal vaccine

:30

Bill Hausdorff joined GSK Biologicals in 2003, and is currently Vice President and VaccineDevelopment Leader for Pneumococcal Vaccines, based in Wavre, Belgium. Prior to that positionhe served as VP and as Director of Epidemiology and Scientific Strategy at GSK.

His academic background includes a PhD in Biology from Johns Hopkins University/the US NationalInstitutes of Health, and a post-doctoral fellowship in molecular pharmacology at Duke Universityin the US. Subsequently he served as a Technical Advisor with the US Centers for Disease Controland Prevention, based at the US Agency for International Development in Washington DC andCairo, Egypt. There he worked to expedite introduction of new vaccines into developing countryimmunisation programs. In 1995 he joined Wyeth Vaccines in the Scientific Affairs and ResearchStrategy group, where he participated in the development of pneumococcal conjugate vaccines.

His major focus at GSK Biologicals is on the development and introduction of vaccines to preventdiseases caused by the pneumococcus, Haemophilus influenzae, meningococcus, rotavirus, and

pathogens respresented in DTP-combination vaccines. He is the author of numerous scientific articles and book chapters,

including extensive publications on the epidemiology ofS. pneumoniaedisease.

Dr William Hausdorff


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M E N I N G I T I S A N D S E P T I C A E M I A I N C H I L D R E N A N D A D U L T S W E D N E S D A Y 9 N O V E M B E R 2 0 1 1 M E N I N G I T I S A N D S E P T I C A E M I A I N C H I L D R E N A N D A D U L T S W E D N E S D A Y 9 N O V E M B E R 2 0 1 1 21

Breakfast Wednesday 9 November 2011Breakfast Wednesday 9 November 2011

REGISTRATION AND COFFEE00

NOVARTIS SATELLITE BRE AKFAST SESSIONReal lives, real costs; the toll of meningococcal disease

20

Dr Peter Dull, Novartis Vaccines and Diagnostics, Cambridge,MA, USABiography on page 13

air:

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

He completed his higher surgical training at the University of Manchester and fellowshiptraining at the Royal Alexandra Hospital for Children, Sydney, Australia.

He has a broad based practice with a special interest in limb reconstruction surgery using aspectrum of contemporary techniques. He has considerable experience in the management ofpatients with the skeletal consequences of septicaemia and contributes to a multi-disciplinaryteam specifically managing this patient group. He is active in all aspects of paediatric traumaand has published on this subject.

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

Mr Fergal Monsell, MSc PhD FRCS(Orth), Royal Hospital for Children,Bristol Immediate impact: Musculo-skeletal impacts of meningococcaldisease

Mr Fergal Monsell

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

Dr Liam Dorris D.Clin.Psych BSc (Hons) AFBPsS, Consultant PaediatricNeuropsychologist & Honorary Senior Clinical Lecturer, Royal Hospital

for Sick Children, GlasgowSocietal impact: Psychosocial impacts of meningococcal disease

Dr Liam Dorris

Notes

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

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

Dr Clarke has published more than 80 peer-reviewed papers mainly in the field ofN. meningitidis andS. pneumoniae infection. In 2009, Dr Clarke won the Bupa Foundation's award of best emergingmedical researcher in the UK for his work on the molecular epidemiology of pneumococcal infection around theintroduction of pneumococcal conjugate vaccines.

Dr Stuart C Clarke, Reader in Infectious Disease Epidemiology andHonorary Consultant in Health Protection, University ofSouthampton, UKPublic Health impact: Meningococcal disease outbreaks

Dr Stuart Clarke

Notes

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

WINE RECEPTION, EXHIBITION AND POSTERS8:00


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Morning Wednesday 9 November 2011 Morning Wednesday 9 November 2011

Dr Marc LaForce, Meningitis Vaccine Project, PATH/WHO,Ferney-Voltaire, FranceIntroduction of meningococcal serogroup A vaccine in the Africanmeningitis belt

Dr Marc LaForce joined the Meningitis Vaccine Project as Director in August 2001. He has a long anddistinguished career in disease prevention, vaccinology, and international health. The MeningitisVaccine Project is a partnership between WHO and PATH aimed at developing, testing, licensing andintroducing conjugate meningococcal vaccines in Sub-Saharan Africa.

Dr LaForce earned his Doctor of Medicine degree from Seton Hall College of Medicine and Dentistryin Jersey City, NJ. He completed his internal medicine and infectious disease training on the HarvardService 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 thefaculty at the University of Colorado School of Medicine. He is board certified in internal medicine andinfectious diseases and is a Fellow of the American College of Physicians and the Infectious DiseasesSociety of America. Before joining PATH he was Physician-in-Chief at the Genesee Hospital andProfessor 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, clinicalinfectious diseases, epidemiology and vaccinology.

AbstractA new Group A meningococcal (Men A) conjugate vaccine, MenAfriVac TM, was prequalified by the World HealthOrganization (WHO) in June 2010. Because Burkina Faso has repeatedly suffered meningitis epidemics due to Group ANeisseria meningitidis special efforts were made to conduct a country-wide campaign with the new vaccine in late 2010and before the January 2011 onset of the next epidemic meningococcal disease season. In the ensuing five months(JulyNovember 2010) the following challenges were successfully managed: 1) doing a large safety study and registeringthe new vaccine in Burkina Faso; 2) developing a comprehensive communication plan; 3) strengthening the surveillancesystem with particular attention to improving the capacity for real-time polymerase chain reaction (PCR) testing of spinalfluid specimens; 4) improving cold chain capacity and waste disposal; 5) developing and funding a sound campaignstrategy; and 6) ensuring effective collaboration across all partners. Each of these issues required specific strategies thatwere managed through a WHO-led consortium that included all major partners (Ministry of Health/Burkina Faso, SerumInstitute 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 onDecember 6, 2010, in a national ceremony led by His Excellency Blaise Compaore, the President of Burkina Faso. Theensuing 10-day national campaign was hugely successful, and over 11.4 million Burkinabes between the ages of 1 and29 years (100% of t arget population) were vaccinated. African national immunization programs are capable of achievingvery 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 inmeningitis belt countries.

Dr Marc LaForce

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

Dr Adegbola received his undergraduate education in medical microbiology at the LagosUniversity Teaching Hospital in Nigeria and obtained his Ph.D. in Microbiology from Universityof 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, UKappointed him an Honorary Visiting Professor on 1 May 2005. He has over 20 years research experience with over167 journal publications and 5 book chapters in bacterial infections of the tropics particularly, pneumonia andmeningitis, caused byStreptococcus pneumoniae, Haemophilus influenzae type band Neisseria meningitidis in youngchildren.

At the Gates Foundation, Dr Adegbolas role is taking pneumonia and meningitis research findings to policy,implementation and evaluation for impact. He is responsible for vaccine impact studies, including impact evaluationsfor pneumococcal and meningococcal conjugate vaccines and maternal immunization program and for studies of themicrobial 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 diseasedecimates communities, killing about 10% of affected people, leaving 25% of survivors with sequelae such as braindamage or deafness and rendering a struggling health care system completely overwhelmed. A population of 400million 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 yearsbut the vaccines are used f or re-active mass vaccination campaigns along with antimicrobial treatments for epidemiccontainment only. They neither provide long-lasting protection nor confer herd immunity, particularly in youngchildren who are at highest risk for disease. A quadrivalent protein-polysaccharide conjugate vaccine containingmeningococcal serogroups A, C, Y and W135 and monovalent group C conjugate vaccine with a more lastingprotection against meningococcal disease have been introduced in developed countries but these vaccines are at a costthat 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 20,000deaths with as yet undisclosed number of survivors with sequelae. This generated a major concern among the publichealth officials of the affected communities to which they drew a global attention. Consequently the MeningitisVaccine Project (MVP), a partnership between WHO and PATH, was formed with funding from the Gates Foundationin 2001 to address the prevention and ultimately the elimination of epidemic meningitis in Sub-Saharan Africa. The

Prof Richard Adegbola, Bill & Melinda Gates FoundationBill & Melinda Gates Foundation activity to combat meningitis

in Africa

10:20

Prof Richard Adegbola

Notes

Tackling meningitis in Africa

Professor Robert Heyderman, Malawi-Liverpool-Wellcome TrustBiography on page 15

hair:

Abstract

MenAfriCar (the African Meningococcal Carriage Consortium) is a global research effort to study how meningococci arespread 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 and11 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 rainyseason between September and December 2010. Detailed longitudinal studies were also performed in households wherea 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. Theprevalence of meningococcal carriage overall was low at around 4% and serogroup A carriers were only identified inChad. The implications of these results for the design of the subsequent stages of the study will be discussed. Severalmethodological challenges were encountered, including difficulties with serogrouping using slide agglutination, andimplementation of a new data management system. A brief update on the current activities in the second round ofsurveys will also be given.

Notes

20

Dr Caroline Trotter, University of BristolCarriage and spread of meningococcus in the meningitis belt:the MenAfriCar projectBiography on page 14

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Morning Wednesday 9 November 2011Morning Wednesday 9 November 2011

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 TransportService. His research interests started in laboratory studies in innate immunity and cellularadhesion and have developed into clinical studies in children with critical illnesses includingtrauma, sepsis and respiratory failure. He chairs the Paediatric Intensive Care Society StudyGroup and the Medicines for Children Research Network Clinical Studies Group forAnaesthesia, Pain, Intensive Care and Cardiology.

Abstract

Observational studies in septic shock associate improvements in outcome with early and rapidfluid 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 albuminsolution 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 summarymeasures of the adequacy of oxygen delivery (ScvO2 or lactate clearance) to guide resuscitation. These studies implythat traditional goals of heart rate, blood pressure and perfusion are inadequate and more fluid and more inotropetherapy may rescue more patients. The very early septic shock deaths seen in the UK may be improved by simpleadherence to existing protocols.

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

Dr Mark Peters, Institute of Child Health, University College LondonOverview of evidence for managing children with sepsis, includingfluid management of children in shock

11:50

Notes

Simon Nadel has been a Consultant in Paediatric Intensive Care since 1994. Prior to this hetrained in paediatric infectious diseases. He has been involved in coordinating and runningtherapeutic trials in children with meningococcal and other septic shock, and has taken part inresearch studies into the pathophysiology, treatment and outcome of meningococcal diseasein children. He has been involved in writing clinical guidelines for the management of childrenwith septicaemia and meningitis.

Dr Simon Nadel

s

Current issues in recognition and treatment

Dr Simon Nadel, St Marys Hospital, Imperial College LondonChair:

Dr Nelly Ninis is currently a consultant in General Paediatrics at St Marys Hospital, Paddington.She has completed training in paediatric infectious diseases and immunology and has an Mscin tropical medicine. She worked for three years on the Paediatric Intensive Care Unit at StMarys when it was a specialist referral unit for meningococcal sepsis.

She conducted the RCPCH study on healthcare delivery and the outcome of meningococcaldisease in children, funded by Meningitis Research Foundation. From this study she hasdeveloped 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.

Dr Nelly Ninis, St Marys Hospital, Imperial College LondonPitfalls in recognition of meningitis and septicaemia in teenagers

1:20

Dr Nelly Ninis

s

vision was to:

n Develop a meningococcal conjugate vaccine and evaluate it in Africa

n Create a pathway for the licensure of vaccine to be used largely in Africa

n Assure production in sufficient volume to meet projected needs

n Monitor throughout to assure the effectiveness and safety of the intervention

n Finance the procurement of vaccine through existing or new global programs

n 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 affectedcountries in the meningitis belt.

After 10 years of Research and Development including safety, immunogenicity and antibody persistence studies anda process of licensure in India and WHO pre-qualification in June 2010, MenAfriVac became the first vaccinedeveloped 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 atcollecting data required for licensure for infant indication.


sAbstract

There have been great improvements in the medical management of children with meningitis and septicaemia overthe 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 inevidence-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 outcomefrom sepsis in adults.

But how about the grey area of late adolescence? It is known that older teenagers have increased rates ofmeningococcal disease and higher case fatality rates than younger children. It is also known that teenagers areundergoing a metamorphosis from childhood to adulthood with physical changes occuring both in their bodies andbrains. 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 onlyphysical but also emotional, educational and social. These outcomes are worse than for younger children. Follow uprates 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 theyalways taken seriously when they present. Do they present late to doctors as it is assumed they are hungover or justbeing wimps? Does the fact they are able to compensate well in sepsis make recognition of disease severity moredifficult?

I would like to propose that we set up an adolescents sepsis UK task force to set standards for the care of adolescentswith sepsis and particularly meningococcal disease. We need to bring together experts in paediatric and adult intensivecare and adolescent physcians to mount a campaign to raise the profile of young people with sepsis. As I am actuallynot an expert in any of these fields, I propose to take the minutes and make the coffee! I welcome your interest.

Notes

Dr Mark Peters


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Afternoon Wednesday 9 November 2011Afternoon Wednesday 9 November 2011

Paul is a medical epidemiologist who joined the HPA in 2009. After several years as a hospitalphysician and periods working in epidemiological research in the UK and abroad, he retrainedin public health and epidemiology. Since becoming HPA NW regional epidemiologist he has led

the epidemiological investigation of a number of regional and national infectious diseaseoutbreaks. His current research projects relate to Clostridium difficile and influenza and he hasan ongoing interest in the use of advanced statistical methods in epidemiology.

Abstract

Invasive group B meningococcal disease remains a cause of significant morbidity and mortalityin the United Kingdom. Most disease occurs sporadically but localised outbreaks occur, andavailable public health interventions are limited. Dr Cleary will describe the investigation andpublic 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 ameningococcal carriage prevalence study undertaken in West Cumbria to attempt to better understand thetransmission of disease in this setting.

Dr Paul Cleary, HPA Northwest, LiverpoolDealing with a localised MenB epidemic the Cumbrian situation

14:25

Dr Paul Cleary

Notes

Prevention of meningococcal disease

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 serologicalresponses to various bacterial and viral vaccines with a special interest in meningococcal andpneumococcal vaccines. He is also the Deputy Head of the HPA Meningococcal Reference Unitfor England & Wales. He gained his PhD in 1994, his MRCPath in 2003, became an HonoraryProfessor of Vaccine Preventable Diseases at the University of Manchester in 2009 and VisitingProfessor of the Manchester Metropolitan University in 2011. His scientific findings resulted inover 190 peer reviewed published papers. He serves as a member of the DoH Joint Committeeon Vaccination and Immunisation (JCVI) and frequently advises WHO and companies on bothmeningococcal and pneumococcal vaccines. He sits on the medical-scientific advisory panelsfor Meningitis Research Foundation, Meningitis UK and Meningitis Trust.Prof Ray Borrow

Professor Ray Borrow, Vaccine Evaluation Unit, Health Protection Agency, Manchester

air:

Andrew J Pollard, FRCPCH PhD, is Professor of Paediatric Infection and Immunity at theUniversity 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 StCross College and Honorary Consultant Paediatrician at the Childrens Hospital, Oxford, UK.He obtained his medical degree at St Bartholomews Hospital Medical School, University ofLondon in 1989 and trained in paediatrics at Birmingham Childrens Hospital, UK, specialisingin Paediatric Infectious Diseases at St Marys Hospital, London, UK and at British ColumbiaChildrens Hospital, Vancouver, Canada. He obtained his PhD at St Marys Hospital, London,UK in 1999 studying immunity to Neisseria meningitidis in children and proceeded to work onanti-bacterial innate immune responses in children in Canada before returning to his currentposition at the University of Oxford, UK in 2001. He chaired the UKs NICE meningitisguidelines development group, and chairs the NICE topic expert group developing qualitystandards 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 paediatricresearch groups in the UK with 70 staff. Current research activities include clinical trials of new and improved vaccinesfor 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. Hispublications include over 200 manuscripts and books on various topics in paediatrics, infectious diseases, and highaltitude medicine.

Abstract

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

Professor Andrew Pollard, University of OxfordChanges to UK immunisation programme, including prospects for ateenage meningococcal booster

14:00

Prof Andrew Pollard

Notes


Mervyn Singer is Professor of Intensive Care Medicine at University College London. He has amajor research interest in sepsis and multi-organ failure and champions the key role ofmitochondria in causing organ dysfunction. He is an NIHR Senior Investigator and his researchis funded by the Wellcome Trust, MRC, EU and NIHR. He has had major involvement in anumber 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 thegeneral process of care rather than specific innovations. High-profile campaigns havepromoted 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 adilemma of which we are becoming increasingly aware, namely that our drugs andtechnologies 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 'theend of the bed'. Our current lack of sophistication in immune, hormonal and metabolic monitoring fails to detect thesecovert changes. This monitoring deficiency may also be responsible in large part for the repeated failure of high-profileand high-expense multi-centre trials attempting to modulate the immune process. Thus, the frequent inability todeliver the right dose to the right patient at the right time and for the right duration may contribute to the overallneutral or even negative outcomes of these studies. The subsets who may have benefitted are diluted or cancelled outby those where it did not deliver a positive effect. There is a considerable push at present to develop novel biomarkersto identify infection, sepsis and organ dysfunction at an early stage, and to prognosticate. This will probably assistgreatly in identifying appropriate patients for treatment. This will also be allied with a greater appreciation of thepathophysiology underlying sepsis, and recognition that many seemingly 'negative' consequences may actuallyrepresent intrinsic attempts at adaptation which should be perhaps supported rather than reversed by ourmanagement.

Professor Mervyn Singer, University College LondonCurrent advances in sepsis management in adults

:20

Prof Mervyn Singer

LUNCH, EXHIBITION AND POSTERS:50

AWARD FOR BEST POSTEROn behalf of the Steering Committee, Professor David Lalloo will announce the award for best poster.The prize has been kindly donated by Pfizer.

:50

Prof Mervyn Singer


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Afternoon Wednesday 9 November 2011Afternoon Wednesday 9 November 2011

Dr Jansen left Merck in October 2004 to join VaxGen as Chief Scientific Officer and Senior Vice President for Researchand Development with responsibility for VaxGens 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. Shebrings a recognised series of accomplishments, as well as an established international reputation in vaccine discoveryresearch and development.

Abstract

Pfizer is developing a bivalent factor H binding protein (fHBP/LP2086) vaccine to prevent Neisseria meningitidisserogroup B (MnB) disease. fHBP, an outer membrane lipoprotein, protects MnB from complement attack. More than2,500 invasive MnB disease isolates in addition to carriage isolates have been studied. IMDB and carriage isolates allcontain 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 toachieve robust serum bactericidal antibody responses and broad coverage of disease isolates. Vaccine coverage in thecontext of fHBP sequence diversity is an important consideration for licensure, and post-licensure surveillance withappropriate surveillance mechanisms. fHBP sequences, expression levels, patient ag

Meningitis Septicaemia Conference

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