Ebola Conference 2015

Programme Co-Chairs

Ebola 2015 Report by Dr Sian Reece-Loram, Public Health England, UK

Challenging Ebola with a United Front

The current Ebola virus outbreak is the worst and the most serious one in history, with over 10,000 recorded deaths to-date, and posing considerable threat of spreading outside Africa. This conference is being planned in order to bring together those involved in Ebola research and containment onto a single platform, to share experiences and to find the way forward. Furthermore, we hope that by mid-January 2015 (the time of the conference), we would start seeing results of the containment efforts, outbreak trends, the course the virus had taken outside West Africa, plus early results of vaccine clinical trials; therefore, this conference would also be an excellent ‘progress review’ opportunity.

Conference Sessions:

Public health challenges of EVD
EVD Case management
Laboratory diagnosis
Modelling and transmission of EVD
Immunotherapy and antivirals
Containment strategies and risk assessment

Target Audience: Healthcare and health protection professionals, virologists, vaccinologists, mathematical modellers, epidemiologists and policy makers

Please contact us on Ebola@lpmhealthcare.com if you have any questions.

Ebola Resources and News:

Speakers and Agenda

Session 1: Challenges of EVD

16.00: Housekeeping

16.10: Opening remarks by Professors Maria Zambon & Frederick Hayden (Programme Co-Chairs)

16.20: Inauguration by Professor David Heymann BA MD CBE

Chairman, Public Health England, & Head of the Centre on Global Health Security, Chatham House, London, UK

Global health emergencies

16.50: Professor Chris Whitty DSc FMedSci FRCP

Chief Scientific Advisor & Director Research & Evidence, UK Department for International Development (DFID), London, UK

The UK overseas response to the Ebola epidemic (view abstract)

17.20: Professor John Watson MBBS MSc FRCP FFPH

Deputy Chief Medical Officer, Department of Health, London, UK

The response within the UK to the Ebola outbreak in West Africa (view abstract)

17.50: Dr Julia Amos DPhil

Research Associate, Oxford Department of International Development and Research Fellow in Global Wellbeing, Merton College, Oxford, UK

The political and economic dynamics of Ebola Virus Disease (EVD) in Sierra Leone (view abstract)

18.10: Dr Amenda Semper PhD

Rare and Imported Pathogens Laboratory, Public Health England, UK

Developing laboratory capability in Sierra Leone

18.25: Dr Christopher Logue PhD

Senior Virologist, Novel and Dangerous Pathogens Training, Public Health England, Porton Down, UK; Adjunct Professor of Virology, Universidad San Francisco de Quito (USFQ), Ecuador; and Honorary Fellow, Clinical Infection Microbiology & Immunology, University of Liverpool, UK

European mobile labs in West Africa: Supporting EVD diagnosis (view abstract)

18.40: Close of Day 1

19.00: Networking Dinner (by invitation or prior booking only)

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Session 2: EVD Case Management

9.00: Welcome by Professor Maria Zambon

9.10: Professor Fred Hayden MD

Professor of Medicine, Infectious Diseases and International Health, School of Medicine, University of Virginia, Charlottesville, VA, USA

Overview of Ebola therapeutics

9.40: Dr Tim Fletcher MBBS PhD

Liverpool School of Tropical Medicine, University of Liverpool, UK

Hospital set up and field management

10.00: Dr Colin S Brown

King’s Centre for Global Health, King’s Health Partners, King’s College London, Weston Education Centre, London, UK

Treating EVD patients in the field (view abstract)

10.20: Lt Col (Dr) Mark S Bailey MD FRCP FFTM DTM&H RAMC

Consultant Physician & Associate Professor in Infectious Diseases & Tropical Medicine, Birmingham Heartlands Hospital, Warwick Medical School & Royal Centre for Defence Medicine, Birmingham, UK

Case management at the British Army Ebola Treatment Centre in Sierra Leone

10.40: Refreshment Break

Session 3: Laboratory Diagnosis

11.15: Dr Professor Miles Carroll PhD/ Dr Roger Hewson PhD

Deputy Director of Research, Public Health England, Porton Down, UK

Filovirus research at PHE and the EML lab in Guinea

11.45: Dr Robin Gopal PhD

Clinical Scientist, High Containment Microbiology, Public Health England

The challenges of working with live Ebola virus at BSL 4; development of serological tests

12.15: Dr Phil Minor PhD

Head, Division of Virology, National Institute of Biological Standards and Control, South Mimms, UK

Reference preparations for Ebola (view abstracts)

12.45: Lunch Break

Session 4: EVD Immunotherapy and Antivirals

13.45: Professor Trudie Lang PhD

Professor of Global Health Research, Head of The Global Health Network, Senior Research Fellow, Nuffield Department of Medicine, Oxford, UK

Rapid evaluation of potential therapies for Ebola in clinical trials in West Africa

14.05: Professor Sarah Gilbert PhD

Professor of Vaccinology, Programme Director for Wellcome Trust Strategic Award on Human and Veterinary Vaccine Development, Principal Investigator, Oxford Martin Programme on Vaccines, Nuffield Department of Medicine, University of Oxford, Oxford, UK

Vaccine candidates and their selection for phase 2/3 trials based on phase I immunological data (view abstract)

14.25: Dr MG (Calum) Semple PhD FRCPE FRCPCH

Senior Lecturer in Child Health, Consultant Respiratory Paediatrician, Institute of Child Health, University of Liverpool, Alder Hey Children’s Hospital NHS FT, Eaton Road, Liverpool, UK

ISARIC and Convalescent Plasma Studies in West Africa

14.40: Professor the Hon Richard S Tedder UCL FRCPath FRCP

Joint PHE/NHSBT Blood Borne Virus Unit, Virus Reference Department, Microbiology Services, Public Health England, Colindale, United Kingdom

Serology support for EVD convalescent plasma studies (view abstract)

14.55: Professor Antonio Lanzavecchia PhD

Institute Director and Group Leader, Immune Regulation, Institute for Research in Biomedicine, Switzerland

Engineering of human monoclonal antibodies to Ebola virus

15.15: Professor Alain Townsend MD PhD FRS FRCP

Professor of Molecular Immunology, Investigative Medicine Division, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK

Plans for making Humans MAbs during the current Ebola outbreak

15.35: Refreshment Break

Session 5: EVD Modelling and Transmission

15.55: Mr David Pigott

Spatial Ecology and Epidemiology Group, Department of Zoology, University of Oxford, Oxford, UK

Mapping the zoonotic niche of Ebola virus disease in Africa (view abstract)

16.15: Dr Peter D Walsh PhD

University Lecturer, Department of Biological Anthropology, University of Cambridge, UK

Modelling of Ebola wave spread: The current EVD outbreak could have been predicted! (view abstract)

16.30: Dr Simon Cauchemez PhD

Head, Mathematical Modelling of Infectious Diseases Unit, Institut Pasteur, Paris, France

Chains of transmission and control of Ebola Virus Disease in Conakry, Guinea in 2014 (view abstract)

Session 6: Containment and Risk Assessment (debate)

16.50: Debate

Professor David Mabey DM FRCP FMedSci CBE

Professor of Communicable Diseases, London School of Hygiene & Tropical Medicine, London, UK

Proposing: Port screening in the UK/Europe is not a useful public health intervention

Dr Jenny Harries PhD

Regional Director, South of England, Public Health England, UK

Proposing: Port screening in the UK is a useful public health intervention

Discussion from the floor

17.30: Closing remarks by Professors Hayden & Zambon

Posters

Analysis of Requirements for Hospital Utilisation/Resources-From Afghanistan to Africa. Modelling bed requirements for Healthcare Workers in Sierra Leone

Jordan S Low, Charlotte F Vallily, Samantha Rose

Defence Science and Technology Laboratory (Dstl), Portsdown West, Portsdown Hill Road, Fareham, Hampshire, PO17 6AD, UK

The UK response to Ebola is predicated on providing treatment, isolation and triage of infected people in Sierra Leone. Healthcare Workers have been found to be at increased risk for infection in outbreaks of Ebola Virus Disease (EVD). As part of the UK MOD commitment to support Sierra Leone EVD treatment centres have been built including a facility to treat infected Healthcare Workers. In order to estimate the required size of such a facility a model previously developed by Dstl analysts to assist military planners assess hospital capacities in Afghanistan was modified to take into account the nuances of the Sierra Leone situation. The Analysis of Requirements for Hospital utilisation and resources (ARTHUR) model takes estimated healthcare worker infection rates, calculated mortality rates, and population sizes of the different eligible populations and uses statistical distributions to account for the uncertainty involved in likely presentation, mortality rate and bed stay length. Appropriate distributions and rates were determined from the data available through the World Health Organisation, open source reporting and literature. Output from the model has influenced decision making within the MOD as to the size of the facility and the medical rules of eligibility.

A cross-sectional study of Ebola virus disease preparedness and the challenges faced by NHS Trusts across England

Anna Aryee^1,2, Patrick Bogue¹, Posy Stoller³, David Mabey⁴, Sam D Douthwaite¹, Nicholas D Price¹, Thomas CS Martin^1,2

¹ Guy’s and St Thomas’ NHS Foundation Trust, UK

² King’s College London, UK

³La Jolla Country Day, USA

⁴ London School of Hygiene and Tropical Medicine, UK

There is a sustained outbreak of Ebola virus disease (EVD) in West Africa. While the unknowing import of a suspected case is unlikely, travel data modelling suggests that outside West Africa, the UK is among the countries most likely to import a case. As a result, the Chief Medical Officer and Public Health England advised NHS acute trusts in England to prepare for the assessment and early management of suspected cases. We undertook a cross-sectional study, using semi-structured telephone interviews and online surveys, of 150 NHS acute trusts in England to evaluate the level of preparedness of trusts and describe the challenges faced. Outcome measures were designed to assess the degree to which trusts had considered the entire patient pathway, infection control and laboratory processes. Challenges faced were identified through open questions and discussion. Of the 150 Trusts contacted, 112 (75%) responded. All interviewed trusts reported undertaking preparedness activities for suspected EVD cases. Most had considered scenarios involving A&E (97%); however, fewer had considered obstetric (61%) and paediatric scenarios (79%) or prospective clinical decisions including intubation/haemofiltration (75%), treatment ceilings (56%), and cardiac arrest (56%). Challenges encountered included the choice, use, and procurement of PPE (71%), national guidance (62%) and resource allocation/management support (38%). Most trusts (97%) reported being ready to assess suspected cases with 71% having assessed at least one case. We conclude that acute care NHS trusts in England have engaged well with preparedness activities. There was, however, some uncertainty regarding preparations for cases in obstetrics, paediatrics and critical care as well as difficulties with PPE guidance implementation. Planning for future infectious epidemics should ensure generic preparedness is maintained within trusts between infection events, and is supported by early, evidence-based, practical guidance.

Modelling West Africa Ebola Virus Disease Outbreak

Eva Santermans¹, Tapiwa Ganyani¹, Christel Faes¹, Niel Hens^1,2, Diamantis Plachouras³, Chantal Quinten³, Emmanuel Robesyn³, Bertrand Sudre³, Wim Van Bortel³

¹Interuniversity Institute for Biostatistics and statistical Bioinformatics, Hasselt University, Diepenbeek, Belgium

²Centre for Health Economics Research and Modelling Infectious Diseases, Vaccine & Infectious Disease Institute, University of Antwerp, Antwerp, Belgium

³Surveillance and Response Support Unit, European Centre for Disease Prevention and Control

On 22 March 2014, the Guinea Ministry of Health notified WHO about an outbreak of Ebola virus disease (EVD) in Guinea, on the border with Sierra Leone and Liberia. Investigations indicated that the first cases occurred in December 2013. Despite the initial efforts to control it, this outbreak developed to be unprecedented in magnitude and extent and largely exceeds the number of all previous outbreaks since the discovery of the disease in 1976. It is essential to understand and predict the evolution of the outbreak, in order to assess the risks of further spread, and to support the most efficient allocation of resources locally and globally. Up to now, a number of modelling approaches have been used. These models mainly used data at country level, as this was the only publicly available information during the first months. We present the results of modelling based on publicly available sub-country (county) level data, with specific focus on recent hotspots in the affected countries. In our analysis, we used a SEIR compartmental model expressed by a set of ordinary differential equations. Parameter estimates are obtained via Markov Chain Monte Carlo methods. The analysis shows that the evolution of the outbreak is not uniform in the affected region, as there are counties with ongoing exponential increase of cases, while in other counties the disease appears to be under control. Our results demonstrate the high variability among the regions and highlight those where the situation is deteriorating at a faster speed and therefore more in need for control measures. The results will help to prioritize and better target the control measures needed to efficiently use scarce available resources.

Development and lyophilisation of influenza, rabies and filovirus lentiviral pseudotypes for use in neutralisation assay-based diagnostic kits

Stuart Mather (1), Emma Bentley (2), Edward Wright (2), Simon Scott (1) and Nigel Temperton (1)

(1) Viral Pseudotype Unit (Medway), School of Pharmacy, University of Kent, Chatham Maritime, Kent, UK

(2) Viral Pseudotype Unit (Fitzrovia), Faculty of Science and Technology, University of Westminster, London, UK

Pseudotype viruses (PVs) are chimeric, replication-deficient virions that mimic wild-type virus entry mechanisms and can be safely employed in neutralisation assays, bypassing the need for high biosafety requirements and performing comparably to established serological assays. However, PV supernatant necessitates −80◦C long-term storage and cold-chain maintenance during transport, which limits the scope of dissemination and application throughout resource-limited laboratories. We therefore investigated the effects of lyophilisation on influenza, rabies and Marburg PV stability, with a view to developing a pseudotype virus neutralisation assay (PVNA) based kit suitable for affordable global distribution. Infectivity of each PV was calculated after lyophilisation and immediate reconstitution, as well as subsequent to incubation of freeze-dried pellets at varying temperatures, humidities and timepoints. Integrity of glycoprotein structure following treatment was also assessed by employing lyophilised PVs in downstream PVNAs. In the presence of 0.5 M sucrose–PBS cryoprotectant, each freeze-dried pseudotype was stably stored for 4 weeks at up to 37◦C and could be neutralised to the same potency as unlyophilised PVs when employed in PVNAs. Further to this, the ongoing outbreak of Ebola virus in West Africa has exacerbated the need for assays that will permit the virus to be studied more widely in low containment laboratories. To address this we have generated a panel of Ebolavirus PVs and shown them to be sensitive to neutralisation by monoclonal antibodies. These results confirm the viability of a freeze-dried PVNA-based kit and suggest filovirus PV are a suitable source of antigen for neutralisation assays. This could significantly facilitate low-cost, widely applicable serology for a wide portfolio of emerging infectious viruses (www.viralpseudotypeunit.info).

Iminosugars against haemorrhagic fever viruses

Joanna L Miller^1*, Simon G Spiro^1*, Stuart D Dowall², Irene Taylor², Andrew C Sayce¹, Raymond A Dwek¹, Roger Hewson², Nicole Zitzmann¹

^*Equal contributions

¹Antiviral Research Unit, Oxford Glycobiology Institute, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK

²Public Health England, Porton Down, Salisbury, UK

Iminosugars are antiviral against a range of viruses in vitro and in small animal models. This includes viruses that cause chronic disease such as hepatitis B and C, and HIV, as well as viruses which cause acute infections such as influenza A and dengue virus. The antiviral mechanisms of action of iminosugars are manifold and include inhibition of ER alpha glucosidases (host enzymes crucial for correct viral envelope glycoprotein folding), of ion channels (such as the HCV p7 channel) and of host glycolipid biosynthesis, which can impact lipid domains important in the life cycles of some viruses. Iminosugars also have a direct and dampening effect on cytokines that are up-regulated excessively in some viral diseases such as dengue haemorrhagic fever. At least two of these iminosugar targets, i.e. viral envelope glycoproteins and pathological cytokine involvement, are present during ebolavirus infection. We therefore tested the iminosugar N-butyl-deoxynojirimycin (NB-DNJ) for safety in uninfected guinea pigs, and for efficacy in animals infected with a 100% lethal dose of guinea pig adapted ebolavirus (strain Zaire). Guinea pigs were treated with 1850 mg/kg/day (t.i.d.) NB-DNJ. A pilot study was promising with 1 of 4 infected NB-DNJ treated animals surviving and the remaining three showing improved clinical signs, however, a second study could not confirm drug-associated benefits. Details of these studies and insights into antiviral mechanisms of actions of iminosugars will be presented.