UCL DEPARTMENT OF INFECTION AND
POPULATION HEALTH
Report of UCL GRAND CHALLENGE DENGUE WORKSHOP
Date: 15th May 2012
Venue: Gordon House 106 UCL
Participants:
Hector Altamirano (UCL Energy Institute, Barlett Faculty of Architecture, Building, Environmental
Design and Planning, and Archive), Phil Astley (UCL Bartlett School of Construction & Project
Management), Julio Davila (UCL Development Planning Unit, Barlett Faculty ), Andrew Hayward
(Centre for Infectious Disease Epidemiology, UCL Royal Free Hospital Campus), Helen Hopkins
(UCL Grand Challenge of Global Health), Michael Jacobs (Division of Infection and Immunity, UCL
Royal Free Hospital Campus) Michela Mazzon (Division of Infection and Immunity, UCL Royal Free
Hospital Campus), David Napier (Professor of Medical Anthropology, Dept of Anthropology, Faculty
of Social & Historical Sciences, UCL), Adriana Pacheco-Coral (Centre for Infectious Disease
Epidemiology, UCL Royal Free Hospital Campus), Ian Scott (UCL Grand Challenges Programme),
Dave Moore (London School of Tropical Medicine and Hygiene), and Henry Stephens (Centre for
Nephrology Anthony Nolan Laboratories, UCL Royal Free Hospital Campus).
Note-takers: Laura Diaz-Alvarez, Natasha Lelijveld
Apologies: Cordelia Cortart, Snezana Djordjevic, Jay Halbert, Sophie Jacobs, Anne Johnson, Paul
Kellam, Maria Kett, Ka-man Lai, Mark Marsh, John Martin, Pablo Mateos, James Paskins, Catherine
Roberts.
Aim of workshop: The Grand Challenge of Global health dengue workshop aimed to stimulate
multidisciplinary research collaborations in Dengue by bringing together UCL researchers currently
working on Dengue with those who are interested in applying their disciplinary perspective to the
problem.
Potential participants for the meeting were identified by the co-applicant team working with the Grand
Challenges office through
a) Co-applicants in the Global Challenge bid providing details of potentially interested parties.
b) Search of UCL website for those conducting Dengue research or research into other vector
borne diseases.
c) Search of the Infectious Disease Research Network Database of expertise.
UCL Department of Infection and Population Health
Centre for Infectious Diseases Epidemiology
University College London Hampstead Campus Rowland Hill Street London NW3 2PF
Tel: +44 (0)20 7472 6777
www.ucl.ac.uk
d) Identification of key academics with interest in impact of climate change, urbanization, and
global health.
e) The Lancet Healthy cities commission group.
Presentations:
Grand Challenge of Global Health
Ian Scott PhD (Principal Facilitator UCL, Grand Challenges Office)
The presentation covered the role of at UCL in facilitating cross-disciplinary work addressing major
Global Health issues and the added value that might be achieved through cross-disciplinary working;
the importance of Dengue and global changes that might impact its control such as climate change,
urbanization and increased global travel. He suggested the possibility of working towards published
report on Dengue.
Dengue & disease pathogenesis: the need of new strategies
Dr Michael Jacobs (Consultant & Senior Lecturer in Infectious Diseases, UCL, Royal Free Hospital)
The presentation covered the global burden of Dengue (currently, an average of 100 million cases
have occurred annually since 2000). The size of the population at risk of Dengue has increased to
approximately 3.5 billion people worldwide due to geographical expansion of Aedes aegypti and the
co-circulation of the four serotypes in the same region); the global distribution of disease (Dengue is
distributed across tropical regions especially Americas, Africa and Asia), transmission of Dengue via
Aedes Aegypti (the vector requires clean water to breed, biting habits etc), the viral subtypes (there
are 4 major subtypes), the spectrum of clinical illness caused by dengue (dengue infection can range
from asymptomatic infection through to a febrile illness with rash, headache, severe pain behind the
eyes, stomach ache, exhaustion and muscle and joint pain, and in some cases causes dengue
hemorrhagic fever characterized by usually have bleedings, haemorrhages, shock or death), the
importance of second infections in the development of severe disease (dengue hemorrhagic fever
only occurs in individuals who are subsequently infected with a different strain of Dengue than their
primary infection), the difficulties in development of an effective and safe vaccine (vaccine
development is hindered by concerns that stimulation of an immune response to vaccination may
reproduce the same immunological pathways that predispose to severe dengue infection), the
development of antivirals (Dr Jacobs outlined an international collaboration on Dengue antiviral
development, in which he is involved: the Yale/UCL/Queensland tripartite collaboration). Problems
include the fact that the potential time-window for effective use of antivirals to minimize viral
replication and reduce clinical symptoms is very short, and that costs are likely to be too high for
many endemic countries. Thus the use of antivirals may have minimal population level impact. The
potential importance of vector control to reduce disease burden is recognised, but past failures in
eradication of Aedes aegypti highlight the difficulties of this approach. Dr Jacobs concluded that there
is a need for new strategies to tackle Dengue.
Immunogenic Associations with Dengue
Dr Henry Stephens, (Consultant Clinical Scientist & Honorary Senior Lecturer in Immunogenetics,
UCL Centre for Nephrology and Anthony Nolan Laboratories, Royal Free Hospital.
Recently published genome-wide association studies for Dengue shock syndrome (Nature Genetics
43:1139, 2011) and a range of HLA/MHC association studies (Stephens H, Curr.Top. Microbiol.
Immunol. 338: 99-114, 2010) suggest great potential for immunigenetics research in primary and
secondary dengue infection. The Anthony Nolan Research Institute hosts the international
ImMunoGeneTics project/HLA Database (IMGT/HLA Database http://www.ebi.ac.uk/imgt/hla/) placing
UCL in a strong position to lead research on genetic associations with Dengue. Dr Stephenson
outlined existing UCL collaborations in Thailand investigating immunogenetic associations with
primary and secondary dengue, associations with disease severity and immunogenetic associations
with serotype.
The presentation led to discussions of the importance of such studies having access to wellcharacterised genetic material from across the infection and severity spectrum and from different
geographical areas/ethnic groups. The need for research understanding the role of T cells in Dengue
protection and pathogenesis was also highlighted.
Community participation control, social factors and Dengue
Dr Adriana Pacheco-Coral (MPhil/PhD Research Student Department Infection & Population Health,
UCL, Royal Free Hospital)
Dr Pacheco-Coral gave an overview of the history of international guidance on Dengue control and
the increasing recognition of the need for community participation as a key part of integrated vector
control strategies alongside environmental sanitation, chemical control of adults and larvae and
biological control. Community participation includes activities to encourage covering of artificial water
containers, washing of water tanks, collection of garbage that can contain water, information and
education and leadership activities. International research has demonstrated the ability of a range of
community based strategies to impact on vector counts (Heintze, C., Garrido, M. V., & Kroeger, A.
2007. What do community-based dengue control programmes achieve? A systematic review of
published evaluations. Transactions of the Royal Society of Tropical Medicine and Hygiene, 101, 317325); but have not demonstrated reductions in levels of infection or disease. Dr Pacheco-Coral
outlined her research in Columbia aimed at understanding community knowledge, attitudes and
behaviour towards Dengue control and linking this vector counts within household water tanks
(Pacheco-Coral, A.D.P., Rivas-Muñoz, F. A., Quiñonez Pinzón M. L., Serrato- Pomar I. M. and
Hernandez-Neuta G. E. Evaluation of information, education and communication (iec) strategy for
dengue control in La Dorada, Caldas, Colombia. Trop Med Int Health 2009; 14(Supl. 2):98-274). The
study found that vector counts were higher in households where water tanks were cleaned
infrequently, where men were responsible for household cleaning and where knowledge of the vector
was poor.
The urbanization process and local government: the physical and institutional context of
Dengue
Dr Julio D Davila (Senior Lecturer, UCL Development Planning Unit, and Bartlett Faculty of the Built
Environment)
The need for Aedes Aegypti to breed in clean water collections means that the vector is well adapted
to urban environments and that the global process of urbanization is therefore an important influence
on Dengue. Dr Davila outlined the key drivers of urbanization and the particular problems of
unplanned urbanization with inadequate municipal services and infrastructure. He noted that small
cities tend to grow the fastest and the near doubling of populations living in informal “slum” settings
since 1990. The importance of thinking about urbanization at different geographical levels including
at the scale of the house (e.g. building design, location and water storage – but highlighting that most
buildings are not designed by professionals), neighbourhood (e.g. communal water storage and
rubbish dumps) and city/region (e.g. overall water supply and frequency and availability of sanitation).
The work highlighted how understanding of water usage was critical to understanding of Dengue
control. Other issues such as the transcience of some settlements and the social vulnerability of some
displaced or newly urban populations were also highlighted.
Round table discussions:
Participants split into 2 groups for round table discussions, with one group focusing on biological
factors and the second on environmental/social perspectives before reconvening to explore potential
for further UCL involvement in Dengue research.
The Biomedical perspectives group noted that there are a number of established research groups
internationally already conducting research into the basic science of Dengue, pathogenesis, vaccine
and antiviral development. These include programmes of research funded by Bill and Melinda Gates
foundation (led by John Hopkins University), MRC research on Immunopathogenesis of dengue
haemorrhagic fever (involving collaborators at Imperial and Bristol), NIH funding and WHO Tropical
Disease Research Programme led by University of Melbourne. Much of this work is being conducted
in Asia with comparatively little work in Central and South Americas. Although UCL researchers are
making important contributions to some Dengue collaborations notably in antiviral development and
immunogenetics there does not appear to currently be sufficient “critical mass” of biomedical
researchers with an interest in Dengue for UCL to be a major player in this area.
The environmental/behavioural perspectives group noted that the relative lack of promising
biomedical solutions heighted the need for alternative approaches. The link between Dengue and
increasing global urbanization provides a potentially fruitful area for further research. UCL has major
strengths in Urbanisation Science through the Grand Challenge of Sustainable Cities “Healthy Cities
Group”. Also through the Barlett Faculty, which engages in multidisciplinary research on the built
environment incorporating the Development Planning Unit, the School of Construction and Project
Management and the Centre for Advanced Spatial Analysis. The Department of Geography also has
groups working on urbanization and migration, environmental change and environmental modelling.
UCL also has strong expertise in behavioural sciences and anthropology. All of these were felt to be
highly relevant areas but it was noted that these groups had not as yet applied their work to Dengue.
Examples of suggested potential areas for research included
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Community mobilization strategies interventions
Understanding barriers to community participation in Dengue control
The link between urbanization and Dengue
Urban water supplies and Dengue
The role of migration and displacement in Dengue
The design of households
The mapping of Dengue cases and vectors and relationship with migration
Funding opportunities:
It was noted that whilst international funders were interested in Dengue UCL were not yet ready to
initiate large scale multidisciplinary work in this area. Most funding opportunities are currently biomedically focused. It was felt that working in under-researched Dengue endemic areas such as
Burma or South America might be more attractive to funders. The use of small-scale funding
opportunities such as funds for foreign expertise to visit UCL could be considered.
Next Steps:
It was agreed that the Grand Challenge Dengue group should continue to seek to engage UCL
expertise particularly in environmental and behavioural sciences.
Action - small core group of interested parties to convene to discuss how to take wider engagement
forward.
It was also agreed that a valuable mechanism to encourage collaborative research would be to
collaborate over the refinement of proposed field work in Columbia investigating the impact of
displacement and urbanisation of Dengue control as part of Dr Pacheco-Coral’s PhD.
Action – core group to advice on relevant expertise to input into design and conduct of proposal.
Andrew Hayward
Adriana Pacheco-Coral