Day one abstracts

Day one - 8 November 2011

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

Session 1 - Counting the cost of meningitis and septicaemia; burden of illness

CHAIR

DR MARY RAMSAY
PUBLIC HEALTH ENGLAND, 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. Since 2009 she has been Head of Immunisation at the Health Protection Agency, and now in Public Health England.

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. 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.

Since April this year, her department in Public Health England has now taken on responsibility for implementation and planning of immunisation programmes, requiring her to provide clinical expert leadership to the Screening and Immunisation Teams based in NHS England. Dr Ramsay’s research interests involve establishing the potential role for new vaccines.
DR SHAMEZ LADHANI
PUBLIC HEALTH ENGLAND, LONDON

CURRENT EPIDEMIOLOGY OF MENINGOCOCCAL DISEASE IN THE UK AND EUROPE, INCLUDING ISSUES FOR SURVEILLANCE RELATING TO A MENB VACCINE

Dr Shamez Ladhani Dr Shamez Ladhani completed his medical training at the United Medical and Dental Schools of Guy’s and St Thomas’s Hospitals, London, and subsequently specialised in paediatrics. In 2000, he travelled to Kenya to work as a paediatric registrar in a district hospital and then went on to complete a PhD in genetic epidemiology of vaccine preventable infections. During 2007-2009, he completed the two-year national grid training programme in paediatric infectious diseases at St George’s Hospital in South London. Currently, he works as a paediatric infectious disease consultant at St George’s Hospital, clinical lecturer at St George’s University of London and clinical epidemiologist at Public Health England. He is the clinical lead for enhanced national surveillance of a number of vaccine-preventable infections, including Haemophilus influenzae, S. pneumoniae and N. meningitidis. He is also involved with conducting clinical trials on behalf of the Department of Health to inform national immunisation policy.

ABSTRACT

Neisseria meningitidis is a major cause of morbidity and mortality worldwide. In the United Kingdom, routine immunisation against meningococcal capsular group C (MenC) since 1999 has meant that most invasive meningococcal infections are now caused by meningococcal capsular group B (MenB). Since the early 2000s, however, the incidence of invasive MenB disease has continued to decline across all age groups – a trend that has been observed across many countries in Europe and elsewhere. In England and Wales, Public Health England (PHE) conducts enhanced national surveillance for invasive meningococcal disease (IMD) through its national meningococcal reference unit (MRU). The provision of a free national PCR testing service by the MRU ensures high case ascertainment across all age groups. From 2006/07 to 2012/13, the number of IMD cases declined from 1132 to 799, while the proportion of MenB cases declined from 88% to 78%. The decline in IMD was observed across all age groups and was most marked in children younger than five years, who remain at highest risk. Overall, however, N. meningitidis remains the single most important cause of childhood bacterial meningitis in England and Wales. In adults, recent increases in capsular group Y (MenY) disease appear to have stabilised. On the other hand, MenW cases increased year-on-year, from 18 cases in 2008 to 46 in 2012.

In addition to routine surveillance, PHE routinely assesses the completeness of case ascertainment using a number of different methodologies. In order to better estimate the total burden of meningococcal disease in England, PHE is currently collaborating with the meningitis charities to link multiple national data sources, including the MRU surveillance, electronic reporting of laboratory-confirmed cases, hospitalisation records and death registrations. Preliminary results indicate that, in addition to the ~800 laboratory-confirmed IMD cases annually, a further ~600 hospitalised individuals had a clinical diagnosis of IMD.

Around half of these individuals, however, had been tested PCR-negative for N. meningitidis by the MRU.

In summary, despite the declining trends in IMD incidence, N. meningitidis remains a major cause of serious bacterial infections in children and adults. Most cases are due to MenB and young children remain at highest risk.

Listen to Shamez Ladhani's presentation


KAREN CROCKATT
MEMBER AND AMBASSADOR OF MENINGITIS RESEARCH FOUNDATION

A PARENT’S EXPERIENCE OF MENINGOCOCCAL DISEASE

Karen Crockatt Karen Crockatt works as a Head of Procurement for Ramsay Healthcare. She trained as a nurse many years ago specialising in Theatre and has held various operational management roles within the NHS and private healthcare sectors, including Directorate Management, commissioning roles and Group Procurement. She is an MRF trained befriender and recently appointed Ambassador for the North West. She is also a Trustee for www.littlelegs.org.uk, the charity for children with congenital limb deficiencies or amputations of part of their legs or feet.

Her husband Nick is a European and Middle East Regional Director with a large medical devices company and is also an MRF Ambassador. They have 2 children, Domenico aged 24, who has just graduated from university, and Sofia aged 9.

ABSTRACT

In February 2007, at the age of 2, Karen’s daughter Sofia contracted meningococcal meningitis and septicaemia and as a result lost her left leg below the knee and sustained severe damage to her right leg. She is now the first ever MRF Junior Ambassador and recently ran the Mini Great North Run and raised £10,000 for MRF.
DR HARETH AL-JANABI
UNIVERSITY OF BIRMINGHAM

NEW STUDIES OF QALY LOSS IN PATIENTS AND CARERS; FAMILY IMPACT OF MENINGITIS AND SEPTICAEMIA

Hareth Al-Janabi Dr Hareth Al-Janabi is a Medical Research Council-funded early career fellow at the University of Birmingham. He conducts research on economic issues in healthcare, mainly focusing on the costs and benefits of healthcare treatments. He is currently developing techniques to capture the - normally ignored - impacts of disease and treatments on patients’ families. Before working in academia, Hareth was an economist at the Department of Health and a policy adviser at the Treasury.

ABSTRACT

Background:
Meningitis frequently results in disabling after-effects for the survivor. We investigated whether these after-effects also had an adverse impact on the health of survivors’ family members. Health (QALY) losses for family members, as well as patients, are relevant in economic evaluations (as used by NICE and other bodies). We therefore examined the implications of the findings for economic analyses of prevention strategies for meningitis.

Methods: We conducted a cross-sectional survey with 1600 family members of survivors in the UK. Family members were recruited through Meningitis Research Foundation in May 2012. We generated ‘exposure’ and ‘control’ groups based on whether the family member was close to a survivor who developed after-effects. We measured the impact of after-effects on family members’ health (EQ-5D-5L) scores and analysed the association between family member and survivor health status using multivariable regression modelling. We also examined whether survivor health status affected the health status of multiple family members.

Findings: Health scores were significantly lower for family members ‘exposed’ to after-effects, relative to those family members who were not. This finding persisted when examining only those family members close to a survivor of MenB.

Family members exposed to at least one after- effect from meningitis had 2.3 times higher odds of reporting anxiety and depression. The after-effects of meningitis had an impact on multiple family members, but the impact diminished with social distance from the survivor. Total health losses to the family were projected to be an additional 48% of the health losses to the survivor.

Interpretation:
Meningitis results in significant health losses for the family as well as the patient. In economic and clinical evaluations focused on population health improvement, the potential health gains to both patients and family members should be considered.

PRESENTATION

Listen to Hareth Al-Janabi's presentation

PROF PHILIPPE BEUTELS
UNIVERSITY OF ANTWERP, BELGIUM

HEALTH ECONOMIC EVALUATION FOR PUBLIC HEALTH DECISIONS INVOLVING SEVERE DISEASES WHICH PRIMARILY AFFECT YOUNG CHILDREN – PROBLEMS AND POSSIBLE SOLUTIONS

Philippe Beutels Philippe Beutels holds degrees in Commercial Engineering and Medical Sciences. He has published about 150 contributions in peer-reviewed journals and books and delivered over 100 lectures at scientific symposia, mainly on topics related to health economics, mathematical modelling and epidemiology of infectious diseases. He’s currently Associate Professor at the University of Antwerp, Belgium, where he heads the Centre for Health Economics Research & Modelling Infectious Diseases (CHERMID). He’s also Senior Visiting Fellow at the University of New South Wales, Australia

ABSTRACT

The standard guiding principle for priority setting in health care is based largely, though not exclusively, on the incremental cost per Quality Adjusted Life Year (QALY) gained of new interventions. This rationale is grounded in the utilitarian theory of justice, which focuses on optimal efficiency irrespective of distributional issues. That is, the focus is on maximising health gains under a budget constraint in the population as a whole, without an a priori concern for the characteristics of the intervention or the individuals enjoying the health gains.

When using the QALY as a summary measure of “a healthy life year” in priority setting, some implicit assumptions are made, including: (1) a small QALY decrement for many people (eg, gastroenteritis, acute otitis media) can be as undesirable as a large QALY decrement in few people (eg, meningitis, encephalitis); (2) 1 QALY gained in a child is equal to 1 QALY gained in an elderly person; (3) 1 QALY gained by cure is equal to 1 QALY gained by prevention; (4) a QALY decrement incurred through unhealthy life style choices is equal to the same QALY decrement incurred by chance.

Yet when the general population’s preferences are elicited, they show deviations from these implicit assumptions. For instance, in recent surveys done in Belgium, people believe priority should be given to (1) prevention over cure for severe diseases; (2) prevention over cure for young children; (3) preventing or curing diseases in children, rather than in elderly persons; (4) preventing severe disease in 100 people over preventing non-severe disease in 100,000 people; (5) preventing or curing diseases acquired by chance, rather than those acquired through unhealthy life style choices.

The above observations and potential ways of dealing with knowledge about these preferences, only partially embedded in the current approach to prioritisation, will be discussed focusing on infectious disease prevention.
Decisions on preventing severe disease in children should take account of additional equity considerations. Further research is needed to document these considerations in different contexts.

Session 2 - Advances from research: implications for prevention and treatment



CHAIR

PROF NIGEL KLEIN
GREAT ORMOND STREET CHILDREN’S HOSPITAL AND INSTITUTE OF CHILD HEALTH, UNIVERSITY COLLEGE LONDON

Nigel Klein Professor Nigel Klein is Professor and Consultant in Paediatric Infectious Diseases and Immunology at Great Ormond Street Children’s Hospital, London, and the Institute of Child Health, University College London. He trained at UCL, obtaining degrees in Anatomy and in Medicine. He is currently Head of the Infectious Diseases and Microbiology Unit at ICH. He has been working in the fields of meningitis and sepsis for many years, in both a clinical and academic capacity.
PROF CHRISTOPH TANG
UNIVERSITY OF OXFORD

FACTOR H BINDING PROTEIN AND VACCINE APPROACHES

Christoph Tange Professor Christoph Tang is currently Professor of Cellular Pathology at the Sir William Dunn School of Pathology at the University of Oxford, having recently moved from the Centre for Molecular Microbiology and Infection at Imperial College London. His group studies the pathogenesis and prevention of disease caused by Neisseria meningitidis and Shigella flexneri, particularly during interactions with the host innate immune system. He was previously an MRC Clinician Scientist at the University of Oxford, and completed his PhD at the Royal Postgraduate Medical School on the identification of virulence factors in the fungal pathogen, Aspergillus fumigatus. Christoph originally trained in medicine at the University of Liverpool and spent two years working in The Gambia, West Africa.

ABSTRACT

To cause disease, pathogenic bacteria must avoid detection and elimination by the immune system. Understanding the mechanisms of immune evasion by bacteria is not only informative about the molecular basis of virulence, but can also direct vaccine design and provide clues about why some individuals that become infected develop disease while others remain perfectly well. The meningococcus has evolved several mechanisms that promote resistance against killing by the complement system, an evolutionarily conserved aspect of host immunity. For example, the bacterium expresses a protein at its surface that can recruit a human molecule, named factor H, that switches off the complement system. The implications of this and other mechanisms of complement evasion on the pathogenesis and prevention of meningococcal disease will be discussed.

PROF MICHAEL LEVIN
ST MARY’S HOSPITAL, IMPERIAL COLLEGE LONDON

GENETIC FACTORS ARE WELL ESTABLISHED AS IMPORTANT DETERMINANTS OF BOTH SUSCEPTIBILITY AND OUTCOME OF INFECTIOUS DISEASES.

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.

ABSTRACT

Genetic factors are well established as important determinants of both susceptibility and outcome of infectious diseases.

With support from MRF an initial genome wide study of meningococcal disease was undertaken, which identified susceptibility genes in the factor H region. With support of both MRF and the EU funded EUCLIDS study, two further genome wide association studies have been undertaken using meningococcal disease patients in Austria, Holland and Spain as well as the UK.

The talk will describe ongoing analysis of the three genome wide studies, and their combined meta- analysis to identify the genetic basis of different clinical phenotypes and outcome of meningococcal disease. The importance of genes in regulating important clinical phenotypes such as coagulopathy, acidosis, neutrophil response and need for ventilation will be discussed as well ongoing studies of genes controlling susceptibility.

Listen to Michael Levin's presentation


PROF MARTIN MAIDEN
UNIVERSITY OF OXFORD

TOWARDS GLOBAL GENOMIC DISEASE SURVEILLANCE; THE MENINGITIS RESEARCH FOUNDATION (MRF) MENINGOCOCCUS GENOME LIBRARY AND BEYOND

Martin Maiden After an initial training in microbiology, during which he developed an enduring interest in infectious disease and public health, Martin Maiden’s graduate studies used molecular, genetic, and biochemical techniques to study sugar transport in Escherichia coli. He became interested in multi-disciplinary and evolutionary approaches to investigating biological problems and, after a two- year MRC Training Fellowship, began his independent research career at the National Institute for Biological Standards and Control, where he was a group leader for nine years, including a sabbatical year at the Max-Planck-Institut für Molekulare Genetik, Berlin. In this period he worked mainly on the biology Neisseria meningitidis and its implications for vaccination. In 1997 he moved to a Wellcome Trust Senior Fellowship in Oxford and was appointed Professor of Molecular Epidemiology and a Fellow of Hertford College in 2004. He became a Fellow of the Royal College of Pathologists in 2010 and a Fellow of the Society of Biology in 2012.

ABSTRACT

The MRF Meningococcus Genome Library is a charity-led initiative to provide high-quality genomic epidemiological data for meningococcal disease in England, Wales and Northern Ireland. Funding has been provided to establish the complete genome sequence data for all meningococcal disease isolates submitted to the Public Health England Meningococcal Reference Unit (PHE-MRU) for the epidemiological years 2010-2011, 2011-2012 and 2012-2013. The goal is to provide open-access data for research and surveillance as an exemplar project. It builds on existing collaborations among the MRF, PHE-MRU (Professor Ray Borrow), the Wellcome Trust Sanger Institute (Professor Julian Parkhill), and the University of Oxford (Professor Martin Maiden). An automated pipeline for genome sequence determination has been established, which generates compiled, annotated sequences which are integrated into the PubMLST.org/Neisseria and Neisseria.org websites, facilitating community access and efficient comparison with other data. Meningococcal isolates are cultured and high-quality chromosomal DNA samples prepared at the PHE-MRU. The samples are sent to the Wellcome Trust Sanger Institute, where the sequence data are generated.

The data are automatically downloaded in Oxford, assembled into contiguous sequences and uploaded into the BIGSdb software platform which automatically annotates the genomes at more than 1600 loci and makes the data available via the web. This pipeline has been shown to produce very high quality data efficiently and to date a total of 923 isolates have been completed, with 514 from the epidemiological year 2010-2011 and 409 from 2011- 2012, with the data for 2012-2013 available soon. This provides unparalleled information on the diversity of meningococcal disease isolates in the run-up to possible vaccine implementation.



Session 3 - Group B streptococcal infection and neonatal meningitis



CHAIR

Prof Paul Heath
St George’s University of London

Paul HeathPaul Heath is a Professor / Honorary Consultant in Paediatric Infectious Diseases at St George’s, University of London and Vaccine Institute in London. His training in paediatrics and infectious diseases was at the Royal Children’s Hospital, Melbourne, the John Radcliffe Hospital, Oxford and St George’s Hospital, London. His particular research interests are in the epidemiology of vaccine preventable diseases, in clinical vaccine trials, particularly in at-risk groups, and in perinatal infections.

He coordinates a national neonatal infection surveillance network (neonIN) and recently, a national study on neonatal meningitis. He sits on national committees concerned with meningitis, Group B streptococcus prevention, pneumococcal and Hib infections, neonatal infections and on immunisation policies in children. He is a Fellow of the Royal Australasian College of Physicians, a Fellow of the Royal College of Paediatrics and Child Health, a member of the research committee of the European Society of Paediatric Infectious Diseases and a member of the steering committee of the international Brighton Collaboration on vaccine safety.
DR IFEANYICHUKWU OKIKE
ST GEORGE’S UNIVERSITY OF LONDON

NEONATAL MENINGITIS IN THE UK

Ifeanyichukwu Okike Ifeanyichukwu Okike is a Clinical Research Fellow at St George’s, University of London. He is responsible for coordinating the MRF- funded bacterial meningitis in infants < 90 days of age: burden of disease and assessment of healthcare delivery study (neoMen). Both studies have been collaboration with the British Paediatric Surveillance Unit (BPSU) and Public Health England (PHE).

Dr Okike obtained his medical degree from Uludag University in Bursa, Turkey and did his Internship in Turkey and University Hospital Leuven, Belgium before starting his training in Paediatrics in the UK.

The neoMen study and other population based studies will also help put meningitis in the first three months of life into context at a population level. These projects form part of Okike’s PhD with St George’s, University of London and also part of his Specialist Registrar training in Paediatrics.

ABSTRACT

Previous United Kingdom (UK) studies of meningitis in infants were conducted in the 1980s and 1990s. Both showed decline in associated mortality with no change in the neurodevelopment outcome for survivors (50% of infants having some form of disability at 5 years of age).

Initiatives such as vaccines against some of the causes (Hib: 1992, MenC: 1999 and PCV: 2006) were introduced in order to reduce the burden of disease in children including neonates. Additionally, the RCOG introduced a guideline for the prevention of early onset group B streptococcal (GBS) infection in 2003. NICE guidelines (feverish illness, 2007 and bacterial meningitis 2010) aimed to improve outcome in children.

We undertook a prospective, enhanced population- based active surveillance study in infants <90 days of age in the UK and Ireland using the British Paediatric Surveillance Unit, routine national microbiological surveillance and by parental reporting of cases via meningitis support charities during July 2010 - July 2011.

The overall incidence for UK and Ireland was 0.38/1000 live births (95% CI: 0.35-0.42) and the median age of presentation was 17 days (IQR 4-41 days). The incidence of neonatal (= 28 days) bacterial meningitis was 0.21/1000 (0.18-0.24) in England and Wales. The majority [205/324 (63%)] of cases were admitted from home. In neonates 50% of cases were admitted from home. Non-specific clinical features dominated while fever was absent in 153 (47%) of cases at presentation. GBS (150, 50%) was the leading cause followed by Escherichia coli (40, 13%), Streptococcus pneumoniae (28, 9%) Neisseria meningitidis (23, 8%) and Listeria monocytogenes (11, 4%). 90 (27%) of the cases had a poor outcome (died/suffered complications) at the time of completion of the study questionnaires. Bacterial meningitis in infants <90 days of age remains a significant cause of mortality and morbidity in the UK and Ireland. Despite all the current prevention strategies, the incidence has not changed since the 1980s with GBS remaining the leading pathogen. Our results also show that with the existing initiatives outcome remains unchanged when compared to 16 years ago. It is therefore time to formulate new strategies through better prevention, especially with an effective GBS and other vaccines. One of our ongoing projects is on initiatives with potential for better outcomes through early identification and improved management of cases.

Funding for the neoMen project is by Meningitis Research Foundation (MRF).


DR KAREN SLOBARD
NOVARTIS GLOBAL DEVELOPMENT, USA

NOVARTIS GROUP B STREPTOCOCCUS VACCINE PROGRAMME

Karen Slobard Dr Karen Slobod received her medical degree from McGill University in Montreal, completed a residency in paediatrics and then a fellowship in infectious diseases and immunology at St Jude Children’s Research Hospital in Memphis, TN. She joined the faculty of the Department of Infectious Diseases at St Jude and pursued basic and clinical research in vaccine development. She joined Novartis Vaccines & Diagnostics in 2007 and is currently the head of the Maternal Immunization Global Program Team, responsible for the development of the group B streptococcus maternal vaccine. She is based in Cambridge, Massachusetts, USA.

ABSTRACT

Background: GBS is a leading cause of neonatal sepsis and meningitis. No licensed vaccine exists. Two studies were conducted examining safety and immunogenicity of the Novartis investigational trivalent (serotypes Ia, Ib and III) GBS CRM197- glycoconjugate vaccine, first in non-pregnant and then in pregnant women.

Methods: Dosage (5 or 20 µg of each glycoconjugate), formulation (unadjuvanted or with Al(OH)3) and schedule (1 or 2 injections) were evaluated in non-pregnant Belgian women. Results informed a subsequent study in 320 pregnant South African women examining 5, 2.5 or 0.5 µg dosages (vs placebo) for safety and immunogenicity at baseline and at delivery.

Results: Vaccines were well tolerated with no vaccine-related SAE. All dosages and formulations were immunogenic (ELISA). GMC (µg/ml; combining data across groups) obtained on day 61 among non- pregnant women revealed no added benefit from 20 vs 5 µg dosage (11.6 vs 14.4 µg/ml); 2 vs 1 injection (11.8 vs 14.1 µg/ml) or adjuvant vs no adjuvant (10.4 vs 16.0 µg /ml). Accordingly, pregnant women received 1 injection of unadjuvanted vaccine at dosages = 5 µg. Responses to 0.5 µg trended lower than those to 2.5 or 5 µg for all serotypes. Among pregnant women with undetectable Ia-specific Ab at baseline, highest Ab responses occurred after 5 µg (6.5 µg /ml) vs 2.5 µg (3.2 µg /ml) or 0.5 µg (2.43 µg / ml; serotype Ia) dosages.

Conclusions: Data support use of a single injection of 5 µg (each glycoconjugate) of unadjuvanted trivalent vaccine to larger scale studies in pregnant women.




Session 4 - Tackling meningitis in Africa



CHAIR

PROF BRIAN GREENWOOD
LONDON SCHOOL OF HYGIENE AND TROPICAL MEDICINE

Brian Greenwood Brian Greenwood qualified in medicine at the University of Cambridge, UK in 1962. Following house-officer appointments in London, he spent 3 years in Western Nigeria as a medical registrar and research fellow at University College Hospital, Ibadan. After receiving training in clinical immunology in the UK, he returned to Nigeria in 1970, this time to help in establishing a new medical school at Ahmadu Bello University, Zaria where he developed his research interests in malaria and meningococcal disease whilst continuing to teach and practice clinical medicine.

In 1980, he moved to the UK Medical Research Council Laboratories in The Gambia which he directed for the next 15 years. In The Gambia, he helped to establish a multi-disciplinary research programme which focused on some of the most important infectious diseases prevalent in The Gambia and neighbouring countries such as malaria, pneumonia, measles, meningitis, hepatitis and HIV. Work undertaken during this period included demonstration of the efficacy of insecticide treated bednets in preventing death from malaria in African children and demonstration of the impact of Haemophilus influenzae type b and pneumococcal conjugate vaccines when deployed in sub-Saharan Africa.

In 1996, he was appointed to the staff of the London School of Hygiene and Tropical Medicine where he is now Manson Professor of Clinical Tropical Medicine. From 2001-2009 he directed the Gates Malaria Partnership which supported a programme of research and capacity development in many countries in Africa directed at improving treatment and prevention of malaria. In 2008, he became director of a new capacity development initiative supported by the Wellcome Trust and the Bill and Melinda Gates Foundation, the Malaria Capacity Development Consortium (MCDC), which operates a post-graduate malaria training programme in five countries in sub-Saharan Africa, and he also directs a consortium (MenAfriCar) established with support from the Wellcome Trust and the Bill and Melinda Gates Foundation to study meningococcal carriage in Africa.
PROF TOM HARRISON
ST GEORGE’S UNIVERSITY LONDON

CONFRONTING CRYPTOCOCCAL MENINGITIS IN AFRICA; NEW DIAGNOSTIC, PREVENTION AND TREATMENT STRATEGIES TO REDUCE DISEASE BURDEN

Tom Harrison Tom Harrison is Professor of Infectious Diseases and Medicine, and Joint Head of the Research Centre for Infection and Immunity, at St George’s University of London, and Honorary Consultant at St George’s NHS HealthCare Trust. He trained in Infectious Diseases in London and in Boston USA. His initial research training was in the laboratory of Professor Stuart Levitz in Boston, where he worked on immune responses to Cryptococcus neoformans.

Clinical research training was through the programmes in Clinical Effectiveness and International Health at Harvard Medical School, and though clinical trial work, developed first in Thailand in collaboration with the Wellcome Trust Bangkok Unit, and subsequently in Cape Town, Mbarara, Uganda, and Lilongwe, Malawi.

He has served on the cryptococcal guidelines panels of the Infectious Diseases Society of America, The Southern African HIV Clinicians Society, and the WHO.

ABSTRACT

Cryptococcosis remains a very common opportunistic infection in HIV-infected patients, and is now the leading cause of adult meningitis in many parts of sub-Saharan Africa. Despite expansion of antiretroviral programmes, cases have not decreased in most African centres. Furthermore, treatment is unsatisfactory: in Africa, mortality has ranged from 24% at 10 weeks in a trial setting in South Africa, to >50% in cohorts treated with fluconazole. A recent CDC analysis estimated the 3 month associated mortality in Africa to be 70%. The combination of high incidence and difficulties with treatment mean cryptococcal meningitis is a very common cause of death in AIDS patients, accounting for up to 20% of all AIDS-related deaths in some cohorts. While tuberculosis is much more common, treatment is available and effective; the high case fatality rate for cryptococcal meningitis drives a high death toll. The CDC analysis estimated that cryptococcal disease is associated with at least 100,000 deaths per year in Sub-Saharan Africa alone.

Drivers of the high case fatality rate include the inadequacy of current antifungal regimens and late presentation. A new point-of-care immunodiagnostic test has the potential to enable earlier, primary care-based, diagnosis for all symptomatic cases. In addition, the test can facilitate screening and pre- emptive treatment as a cost-effective preventative strategy in patients with late-stage HIV infection in areas of high incidence. While drug discovery aimed specifically at Cryptococcus species is very limited, improving access to, and optimising our use of, current antifungal drugs, including in resource-limited settings, together with systematic management of the common complication of raised CSF pressure, and improved diagnosis, has the potential to significantly reduce the global disease burden.





DR DOUMAGOUM MOTO DAUGLA
CENTRE DE SUPPORT EN SANTÉ INTERNATIONALE, CHAD

THE IMPACT OF MENAFRIVAC ON SEROGROUP A INVASIVE MENINGOCOCCAL DISEASE AND CARRIAGE IN CHAD

Doumagoum Moto Daugla Dr Doumagoum Moto Daugla, Director, Centre de Support en Sante Internationale (CSSI) in N’Djamena, Chad is the principal investigator of the Chad arm of the African Meningococcal Carriage Consortium (MenAfriCar).

Dr Daugla studied medicine and specialised in paediatrics at the State University of Leningrad, Russia. He has also undertaken further specialised training in the areas of epidemiology, public health, and management of public health projects. Dr Daugla is a senior public health expert and as such has extensive experience in organising, planning and evaluating services as well as excellent knowledge of the national health policy health system in Chad. In addition to having worked as a paediatrician and holding many positions in various hospitals in Chad, Dr Daugla has also held senior positions within the National Union of Diocesan Associations and the Swiss Tropical Institute.

Dr Daugla is experienced in conducting epidemiological investigations and evaluations of programmes and health projects. In 2000 he led six cross-sectional surveys of the prevalence of HIV/AIDS in Chad. From 2001 to 2002 he was the principal investigator in two studies on human resources of the Ministry of Public Health on behalf of the MOH, WHO N’Djamena and WHO Geneva. In 2004, he was the national consultant on “The study of the socio-economic impacts of HIV/AIDS on the health sector in Chad” on behalf of UNDP. From 2002 to 2010 he was Vice-President of the National Expert Committee on Poliomyelitis in Chad.

Dr Daugla has been the Director of CSSI since 2006 and is the local supervisor to several researchers at different levels (Masters and PhD candidates).

ABSTRACT

Background: A serogroup A meningococcal polysaccharide/tetanus toxoid conjugate vaccine (PsA-TT)(MenAfriVac®) was licensed in India in 2009 and pre-qualified by WHO in 2010 on the basis of its safety and immunogenicity. This vaccine is now being deployed across the African meningitis belt. We have studied the impact of PsA-TT on meningococcal meningitis and carriage in Chad during a serogroup A meningococcal meningitis epidemic.

Methods: Data on the incidence of meningitis before and after vaccination were obtained from national records. In 2012, surveillance was enhanced in the regions where vaccination with PsA-TT had been undertaken the previous year and in three districts where reactive vaccination in response to an outbreak was undertaken. Meningococcal carriage was studied in an age stratified sample of residents of a rural area approximately six months before and after vaccination. Meningococci obtained from cerebrospinal fluid or pharyngeal swabs were characterised by conventional microbiological and by molecular methods.

Results: Approximately 1.8 million subjects aged 1-29 years received a single dose of PsA-TT during the course of a vaccination campaign undertaken in three regions of Chad in and around the capital N’Djamena during a ten-day period in December 2011. The incidence of meningitis during the 2012 meningitis season in these three regions was 2.5 per 105 (57/2.3 x 106) whereas in regions where mass vaccination had not been undertaken it was 43.6 per 105 (3809/8.7 x 106), a 94% difference in incidence (p<0.001). No case of serogroup A meningococcal meningitis was detected in the three vaccinated regions despite reinforced surveillance. Thirty-two serogroup A carriers were identified in 4278 age stratified subjects (0.75%) living in a rural area near to the capital four to six months prior to vaccination whilst only 1 serogroup A meningococcus was isolated in 5001 subjects resident in the same community approximately 6 months following vaccination (adjusted OR =0.019: 95% CI 0.002, 0.14)(p<0.001).

Interpretation: PSA-TT was highly effective at preventing serogroup A invasive meningococcal disease and carriage in Chad. How long this protection will persist needs to be determined.


DR MARIE-PIERRE PRÉZIOSI
ON BEHALF OF THE MENINGITIS VACCINE PROJECT (MVP) AND PARTNERS: MVP IS A PARTNERSHIP BETWEEN PATH AND THE WORLD HEALTH ORGANIZATION (WHO)

ELIMINATION OF MENINGITIS A EPIDEMICS IN AFRICA; MENAFRIVAC FUTURE PLANS

Marie-Pierre Préziosi Marie-Pierre Préziosi was appointed in March 2012 as the new director of the Meningitis Vaccine Project (MVP), a partnership between the World Health Organization (WHO) and PATH, established in 2001 through a grant from the Bill & Melinda Gates Foundation, with the mission to eliminate epidemic meningitis as a public health problem in sub-Saharan Africa through the development, testing, introduction, and widespread use of conjugate meningococcal vaccines.

ABSTRACT

Recurrent meningococcal epidemics have been a major plague for over a century in the African meningitis belt where outbreaks occur annually with large epidemics striking at intervals ranging between 8 and 12 years. The Meningitis Vaccine Project (MVP) is a partnership between the World Health Organization and PATH, funded by the Bill & Melinda Gates Foundation. It was established in 2001 with the mission to eliminate epidemic meningitis as a public health problem in sub-Saharan Africa through the development, testing, licensure, introduction, and widespread use of affordable meningococcal conjugate vaccines.

Following international standards, an affordable MenA conjugate vaccine, MenAfriVac (Serum Institute of India, Ltd), was successfully developed and licensed through an innovative public private partnership. The vaccine was launched at public health scale in December 2010 and has already been introduced into ten African countries through single dose mass campaigns (Benin, Burkina Faso, Cameroon, Chad, Ghana, Mali, Niger, Nigeria, Senegal and Sudan) reaching to date over 112 million persons aged 1- to 29-years, with early results suggesting a major impact on MenA transmission and disease.

The last three epidemic seasons (2011, 2012 and 2013) were characterised by a dramatic fall in cases of group A meningococcal disease in vaccinated countries. The high vaccine coverage achieved augurs well for further rollout of the vaccine in Nigeria and in the additional sixteen countries that constitute the African meningitis belt (Burundi, Central Africa, Côte d’Ivoire, Democratic Republic of Congo, Eritrea, Ethiopia, Guinea, Guinea Bissau, Kenya, Mauritania, Rwanda, South Sudan, The Gambia, Tanzania, Togo and Uganda). Continuing surveillance for cases of meningitis and monitoring of vaccination coverage and safety will be crucial to confirm the effects of the vaccine as it is being introduced across the entire belt. Protecting new birth cohorts through routine vaccination after completion of the mass campaigns, is crucial to sustaining the full impact of MenAfriVac and achieving the overall public health goal. Research from recent and ongoing studies suggest that this could be best achieved through follow-up campaigns and immunisation starting in late infancy.

The presentation will cover the MVP project latest operations and research, including successes to date in implementing the Men A vaccine, key research results and future priorities.



DR NICOLA DESMOND
MALAWI-LIVERPOOL-WELLCOME CLINICAL RESEARCH PROGRAMME, MALAWI

A PILOT STUDY TO ASSESS THE FEASIBILITY OF IMPLEMENTING ETAT TRIAGE COMPONENTS TO FACILITATE RECOGNITION OF SEVERE ILLNESS IN CHILDREN THROUGH MOBILE TECHNOLOGIES AT PRIMARY HEALTH CENTRES IN URBAN BLANTYRE, MALAWI

Nicola Desmond Nicola is a Wellcome Trust Ethics and Society Fellow and Lecturer at Liverpool School of Tropical Medicine. She is a medical anthropologist with over 12 years experience in sub- Saharan Africa currently based at MLW in Blantyre, Malawi where she leads the social science programme. This programme uses high quality mixed methods approaches and qualitative research with a focus on four research areas: social impacts of medical technologies, health seeking behaviour, engagement with health services for prevention and treatment and the bioethics of health research. She is leading work on addressing patient pathways through mHealth technologies at primary health levels in collaboration with Meningitis Research Foundation.

ABSTRACT

Hospital based studies suggest that late presentation is a driving factor for mortality from severe febrile illness in resource-poor contexts. Recent research into health seeking pathways for acute bacterial meningitis at primary health level identified factors linked to service provision and misdiagnoses as contributing to late presentation for appropriate care in tertiary hospitals. These factors include unsystematic and informal triage, high numbers of patients and erratic consultation systems. The aim of this study was to explore the feasibility of implementing a triage system based on the Emergency Triage, Assessment and Treatment (ETAT) protocol recommended by the World Health Organisation (WHO) for resource-poor settings, within 5 Primary Health Centres (PHCs) in Blantyre district referring to Queen Elizabeth Central Hospital (QECH), facilitated through the use of mHealth technologies. We used a mixed methods approach to evaluate whether this implementation will provide a systematic and timely approach to recognising severe illness at PHCs. We conducted a six-month intervention with baseline and post-intervention evaluation components, incorporating a comprehensive training programme for low cadre health workers, Patient Journey Modelling, self completed questionnaires, focus group discussions and semi-structured interviews. Patients were monitored through the system and on reaching QECH to follow up referrals, accuracy of triage outcomes and timeliness of the system.

41,358 paediatric cases were seen overall in five clinics over the six-month intervention period with 101 Emergency, 14,284 Priority and 26,973 non- priority or Queue cases. High levels of agreement (kappa = 0.71) were reached following training between low cadre health worker triage outcomes and clinically trained health staff. Overall 644 (1.6%) cases were referred: 100 of these had been defined as Emergency representing 15.5% of total referrals. A significant number were Priority case referrals (74% of all referrals) whilst 62 cases who had been clinically triaged as non-Priority or Queue, were referred. Of all 644 referrals made, only 240 (37.3%) actually reached QECH, showing a large dropout between primary level referral and arrival at tertiary care. Worryingly 67% of all Emergency referrals never arrived at QECH, but mean time from referral for those Emergency cases that reached QECH was 3.5 hours. The intervention was well received by primary health workers and patients and pre and post evaluation showed a substantial improvement on patient flows and experiences within the clinic.

Our pilot intervention study has shown that establishing an mHealth phone-based triage system is feasible and acceptable at primary health level and that it has the potential to significantly improve patient pathways. We are currently working with the Ministry of Health to develop a full intervention on the impact of the phone-based algorithm and to address other priority gaps in community responses to severe paediatric illness in Malawi.

Meningitis and Septicaemia in Children and Adults 2013's major sponsors are: Conference sponsors

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