Biomarkers to predict severity in dengue infection

Lead Research Organisation: Imperial College London
Department Name: Dept of Medicine

Abstract

Dengue is a mosquito bourne viral infection of the tropics and subtropics. It can lead to a severe haemorrhagic fever that can be fatal unless treated in hospital. At the early stages it is impossible to judge which patients are going to suffer the more severe symptoms and should be admitted to hospital. During epidemics literally thousands of cases can occur at the same time and completely overwhelm the hospital systems. This research aims to develop a simple predictor of disease severity which would allow the high risk patients to be admitted to hospital whilst those at lower risk could be managed at home.

Technical Summary

Dengue virus is an emerging infectious disease the incidence of which is still increasing alarmingly. Most dengue infections are either asymptomatic or mild referred to as dengue fever (DF). However 1-5% of infections can lead to dengue haemorrhagic fever (DHF) that is characterised by a severe vascular leak that can lead to hypovolaemic shock haemorrhage and death. Untreated this condition can be fatal in about 20% whilst expert hospital treatment which consists mainly of careful fluid replacement and monitoring reduces mortality to well below 1%. Dengue puts a huge stress on the healthcare systems in developing countries where explosive outbreaks can literally overwhelm the hospital systems. An effective early test which would stratify patients into high and low risk of developing haemorrhagic fever would be very useful to target the high risk group for hospital admission. It may also have future utility in directing antiviral drug therapy should the current anti-dengue drug programmes come to fruition. At present there is no such early test before the relatively abrupt onset of the vascular leak and shock.

Publications

10 25 50
 
Description HVBD DART 2013 First International Symposium on Human Vector-Borne Diseases Satellite Symposium
Geographic Reach Multiple continents/international 
Policy Influence Type Influenced training of practitioners or researchers
 
Description Wellcome Centre for Clinical Tropical Medicine/Global Health Research annual meeting 2013
Geographic Reach Multiple continents/international 
Policy Influence Type Influenced training of practitioners or researchers
Impact Understanding Dengue pathogenesis and prospects for vaccine
 
Description World Innovation Summit for Health
Geographic Reach Multiple continents/international 
Policy Influence Type Participation in a national consultation
 
Description Biomarkers grant
Amount £700,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 07/2009 
End 06/2012
 
Description DENFREE - Dengue research framework for resisting epidemics in Europe
Amount £494,207 (GBP)
Funding ID 282378 
Organisation European Commission 
Department Seventh Framework Programme (FP7)
Sector Public
Country European Union (EU)
Start 07/2012 
End 06/2016
 
Description Project grants
Amount £300,000 (GBP)
Organisation Cancer Research UK 
Sector Charity/Non Profit
Country United Kingdom
Start 04/2004 
End 04/2007
 
Description Wellcome Trust Enhancement Fund
Amount £192,740 (GBP)
Funding ID 203158/Z/16/Z 
Organisation Wellcome Trust 
Department Wellcome Trust Bloomsbury Centre
Sector Academic/University
Country United Kingdom
Start 06/2016 
End 06/2018
 
Description Wellcome Trust Senior Investigator
Amount £2,800,000 (GBP)
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 10/2012 
End 09/2019
 
Description Dengue clinical centres 
Organisation Mahidol University
Department Siriraj Hospital
Country Thailand 
Sector Hospitals 
PI Contribution We get our samples from Thailand to measure biomarkers
Collaborator Contribution Sample collection and processing
Impact publications
 
Description Felix Rey 
Organisation Pasteur Institute, Paris
Country France 
Sector Academic/University 
PI Contribution We make monoclonal antibodies
Collaborator Contribution Felix Rey at Pasteur solves the structures of antibodies bound to dengue antigens
Impact None yet
Start Year 2011
 
Description Staff Rounds 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Type Of Presentation Paper Presentation
Geographic Reach Local
Primary Audience Health professionals
Results and Impact About 80 health professionals attend these rounds weekly. The presentations are given by different divisions each week and highlight the latest trends in medicine.

Keeping abrest with the latest in medicine and continued professional development.
Year(s) Of Engagement Activity 2006,2007,2008,2009,2010
 
Description 33rd Annual Meeting of the Nordic Society of Clinical Microbiology and Infectious Diseases in Finland 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact I was invited to present my work by the The Nordic Society of Clinical Microbiology and Infectious Diseases.the main topic was to discuss ways to tackle anti-microbial resistance. The first part of the discussion was focused on increased resistance and decreased option and how we can tackle this global issue. I gave my talk on human anti-body responses.
Year(s) Of Engagement Activity 2016
 
Description ASID 2016 Annual Scientific Meeting 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact I was invited to speak at the meeting on my work and also chair a session which I did.I gave my presentation on 'The Antibody Response in Dengue Virus Infection' and chaired the session on 'Antibiotics & Sepsis'. Many professional practitioners, medical students and policy makes alike attended this meeting. As did researchers which was great for further research networking and collaboration.
Year(s) Of Engagement Activity 2016
 
Description Association of Physicians annual meeting 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? Yes
Geographic Reach National
Primary Audience Participants in your research and patient groups
Results and Impact Latest trends in medicine

knowledge of latest trends in medicine
Year(s) Of Engagement Activity 2014
 
Description British Society for Immunology Congress 2013 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Paper Presentation
Geographic Reach National
Primary Audience Health professionals
Results and Impact British Society for Immunology Congress 2013 in Liverpool from 2nd to 5th December. Title was "Protective and pathogenic immunity in dengue virus infection".

Generated interest.
Year(s) Of Engagement Activity 2013
URL http://www.bsicongress.com
 
Description CIDRI Meeting 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? Yes
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Meeting with Prof Bongani M. Mayosi, Head, DoM , UCT
Meeting with Prof Willem (Wim) de Villiers, Dean of Health Sciences, UCT
Meeting with Valerie Mizrahi, Director of IDM (Inst. of ID & Molecular Med)
Talks sparked questions and there were extensive discussions
better understanding of Research Entry awards available to scientists

Improvement of clinical and laboratory facilities for patients and staff.
Further work on co-ordinate research meetings within Africa and facilitate international networking for the benefit of all researchers especially the awardees has been initiated.
Year(s) Of Engagement Activity 2014
URL http://www.cidri.uct.ac.za/
 
Description Chain Florey Workshop 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? Yes
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact the seminars brought latest trends to light

Views on personalised medicine the future
Year(s) Of Engagement Activity 2014
 
Description Co-Chair the MRC Newton Fund, UK-Indonesia: Joint Health Research Call Panel - Research Call on Infectious Diseases 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact This was a meeting to review funding.
Year(s) Of Engagement Activity 2016
 
Description Division of Infectious Diseases Symposium 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Piecing together the Puzzle of Severe Malaria
Keynote presentation: Prof David Salisbury, Head of Immunisation, Public Health England
Latest trends in Infectious diseases

Better understanding of latest trends in Infectious diseases
Year(s) Of Engagement Activity 2014
 
Description GSK Vaccines conference 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact I co-presented my research on vaccine development with one of my collaborators, Prof Felix Rey from Institut Pasteur in Paris. We did a joint a joint seminar on "Certain antibodies isolated from dengue patients not only neutralise all four dengue serotypes, but also Zika virus, providing a structural basis for an epitope-focused vaccine design against both viruses", and met some key people regarding discussion on further vaccine development.
Year(s) Of Engagement Activity 2016
 
Description Grand Challenges conference 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Grand Challenges conference in Beijing, China. I was invited on behalf of the Bill & Melinda Gates Foundation as a speaker to present my work. The Forum was a convening of over 750 key leaders from across the global community to share best practices, encourage collaboration and seek solutions for common challenges. The meeting aimed to build momentum for global health and development innovation and foster scientific collaboration among international groups and researchers. It was co-hosted by the Ministry of Science & Technology, Grand Challenges Canada, the United States Agency for International Development (USAID), Wellcome Trust, the Bill & Melinda Gates Foundation, along with others.
Year(s) Of Engagement Activity 2015
 
Description Guest Lecturer at the UK Society for Microbiology 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Postgraduate students
Results and Impact I was invited to present my work as a guest lecturer at the UK Society for Microbiology in Liverpool. The focus of the conference was Viral haemorrhagic fevers such as Ebola, Zika and Dengue and I presented my work on the Broadly-neutralising antibodies to dengue virus to inform research and policy making.
Year(s) Of Engagement Activity 2016
 
Description International Congress on Medical Virology 2014 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact I lectured on protective and pathogenic immunity in dengue virus infection and it sparked questions.

N.A.
Year(s) Of Engagement Activity 2014
URL http://www.icmv2014.com/
 
Description Interview With BBC 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach Regional
Primary Audience Media (as a channel to the public)
Results and Impact Spread of Knowledge on Dengue

Higher interest Dengue Virus and more awareness
Year(s) Of Engagement Activity 2012
 
Description Multiscale Dynamics Dengue and Zika Virus Conference 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact I was invited to speak and present my research at this conference which was organised by Shee-­Mei Lok and Paul Matsudaira,jointly supported by the Centre for BioImaging Sciences in NUS, the Duke-­NUS Medical School and the Singapore Ministry of Education. Topics ranged fro control and detection to immunity, genome and structural studies.
Year(s) Of Engagement Activity 2016
 
Description Nature Conference Viral Infection and Immune Response 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact I was invited by Wuhan university who held a talk in partnership with Nature Communications to give a talk on my research in immune responses and viral infection. Presentation covered a wide range of topics from Epidemiology of emerging viral disease, Immune intervention and prevention of disease, Persistent viral infection and immune dysregulation to Induction of systemic adaptive immunity. There were also key note speeches given by leading researchers and poster sessions - all of which was very informative.
Year(s) Of Engagement Activity 2016
 
Description Participated in a workshop on immune correlates for dengue 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact I participated in the immune correlates for dengue workshop organised by the PDC - Partnership for Dengue Control and presented on The role of highly neutralizing, cross-reactive antibodies/epitopes. The overall objective was to generate consensus on the current understanding of the immune response to and protection from dengue virus infection, identify key unanswered questions, and address how to improve measurement of efficacy in vaccine trials.
Year(s) Of Engagement Activity 2016
 
Description Presentation at the British Society of Immunology Annual Meeting 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact The purpose was to present my research, meet other researchers and share information and best practice and forge further collaborations.
Year(s) Of Engagement Activity 2015
 
Description Presentation at the Courage Fund for Infectious Diseases 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact This was a conference where I presented on the human antibody response in dengue virus infection. it sparked questions afterwards and let to networking.
Year(s) Of Engagement Activity 2015
 
Description Presentation at the International meeting on Arboviruses and Their Vectors 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact This was a meeting organised by the Society for General Microbiology and the focus of the meeting was on arboviruses and their vectors. Topics such as Interactions of flaviviruses with mosquito vectors and Arboviruses in the conquest of Europe were discussed and spoken about. I presented my work on The human antibody response to dengue virus infection.
Year(s) Of Engagement Activity 2015
 
Description Presented and participated in the Zika Virus Conference in Recife, Barzil 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact I was invited on behalf of CPqAM/Fiocruz, Recife Pernambuco, to participate in the Workshop (ABCDE do Zika Virus). They had put together experts in epidemiology, basic science,
entomologist and other related areas to discuss the recent epidemic of Zika vírus in Brazil which was threatening to become an international health problem.
Year(s) Of Engagement Activity 2016
 
Description Presented at the 3rd Annual DENFREE Meeting 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact I presented my work at the 3rd Annual DENFREE Meeting. This was co-hosted by Pasteur Institute, Paris and DENFREE - Dengue Research Framework for resisting epidemics in Europe. It highlighted the trends in immunology, spoke about what had been achieved so far and what was in store for the future, looked at viral genetic markers, studied the impact on various countries like Bangkok, Cuba and even the US Dengue challenge.
Year(s) Of Engagement Activity 2015
 
Description Presented at the International Symposium on Flaviviruses 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact This was an international symposium on Flaviviruses - Structure and Immunity. There were both oral presentations as well as poster sessions. Many national and international researchers presented their work as did I.
Year(s) Of Engagement Activity 2015
 
Description Royal College of Physicians Advance Medicine Conference - Key Note Speaker and chaired an session 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact The conference was on advance medicine.Topics revolved around Infectious Disease: Chronic Viral Infection, Advances in Hepatitis C , Tuberculosis, Clinical Implications of the Global MDR TB epidemic, Diagnosis and treatment of HIV associated TB, The worldwide threat of emerging infections: update on Dengue Haemorrhagic Fever and other topics replated to Infectious diseases.
Year(s) Of Engagement Activity 2015
 
Description Science Uncovered - Natural History Museum (September 2013) 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? Yes
Geographic Reach National
Primary Audience Schools
Results and Impact Science Uncovered is a widely-advertised and well-attended public outreach event hosted at the Natural History Museum in London, where scientist engage with the public face-to-face basis to discuss their research and its implications in an informal setting. I represented Imperial College London, accompanied by two PhD students, and discussed my group's work, which included the current grant, under the general theme of ecological responses and alterations to energy flux in food webs due to environmental stressors. At our stall we spoke to several hundred visitors throughout the day.

See description above.
Year(s) Of Engagement Activity 2013
 
Description Talk at the Virology Seminar Series at University College London 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact I gave a talk at UCL on my research in Dengue and Zika viruses.
Year(s) Of Engagement Activity 2015
 
Description WHO and NIAID Consultation on Zika Virus Vaccine Development 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact I was invited to USA by the World Health Organisation to present my work on Immune Responses is Dengue and Zika Viruses.
Year(s) Of Engagement Activity 2017
 
Description Wellcome Trust Global Heath Research annual meeting 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? Yes
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Annual update of the centre and progress
Collaboration and capacity development
Research into health problems of the Southern African Region
Global Health Issues

Public Health benefits and research benefits
Year(s) Of Engagement Activity 2014
URL http://www3.imperial.ac.uk/newsandeventspggrp/imperialcollege/centres/globalhealth/eventssummary/eve...
 
Description Wellcome Trust Researchers' meeting: Immunology & Infectious Diseases 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact This is an annual meeting for all PIs and I presented my work and progress at this meeting. Other researchers and professional practitioners were also present and it aided with research trends, making informed decisions and reporting progress as well a further collaboration and funding opportunities.
Year(s) Of Engagement Activity 2016
 
Description Wellcome Trust: Researcher Meeting: Public Health and Tropical Diseases 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? Yes
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact I gave a talk on Dengue Virus which sparked questions afterwards and I have been invited for further conferences.

I have been invited for further conferences
Year(s) Of Engagement Activity 2014