Professor Annelies Wilder-Smith’s research focus over the past 15 years has been dengue. She was the Principal Investigator for the adult cohort in a Phase 2b trial for the chimeric dengue vaccine in Singapore. Furthermore, she is the Lead Principal Investigator of DengueTools, a large international research consortium funded by the European Commission (www.denguetools.net). With a career spanning over two decades, she has led and co-led various clinical trials, published more than 150 scientific papers in international peer reviewed journals, edited and co-edited textbooks and travel medicine books, served on various editorial boards and scientific committees, including being editorial consultant to The Lancet.
Since 2006, she has been consultant to the World Health Organization and co-editor of the annual WHO publication “International travel and Health”. An expert in travel and tropical medicine, she is the President-elect of the International Society of Travel Medicine (ISTM), Past-President of the Asia Pacific Society of Travel Medicine, and was Chair of the Regional Conference of the ISTM in Singapore in 2012.
Her awards include the Myrone Levine Vaccinology Prize, the shared Honor Award for exemplary leadership and coordination in determining and communicating global yellow fever risk presented at the CDC Award Ceremony, the Mercator Professorship award by the German Research Foundation and the Ashdown Oration Award by the Australian College of Travel Medicine.
Prof Wilder-Smith, Umea University is the coordinating body for the DENGUETOOLS project supported by the European Union under the Health Cooperation Work Programme of the 7th Framework programme. Can you tell us a bit about the research that is being conducted in this project?
WS: DengueTools has set out to conduct research in three main areas. The first research area focuses on dengue surveillance. We lack understanding of individual or combined roles of viral, entomological, ecological, environmental and climate factors that influence dengue transmission dynamics and their respective outbreak predictive capability and the most cost-effective approach for surveillance and early warning systems. For surveillance to effectively provide early warning for epidemic transmission, it must be active, laboratorybased, and comprehensive in its coverage of the spectrum of clinical illness and the factors that influence transmission dynamics. We have set out to establish a laboratory enhanced surveillance system in Sri Lanka to study individual and combined factors including cost-effectiveness of surveillance. Furthermore, we have added research on improving entomological surveillance, and point of care diagnostic assays.
The second research area focuses on how to prevent dengue in children in endemic countries. Effective control strategies to protect children are lacking, in particular simple, cost-effective and scalable strategies. We hypothesize that insecticide treated school uniforms may be a target for school based intervention to reduce the incidence of dengue in school children. To test the hypothesis, we have designed a school based randomized controlled trial in Thailand.
Lastly, gaps in understanding the risk of introduction of dengue to non-infected areas, including Europe, hampers effective preventive strategies. We currently have insufficient data on the magnitude and trends of importation and virus evolution over time and by geographic origin. We also only have a poor understanding of vector density, preferred breeding sites, and vectorial capacity of Aedes in temperate climates that are needed for predictive models under changing climate conditions. The third research area hence was set up to address those shortcomings and includes the development of predictive risk modelling and maps under different future climate scenarios in Europe.
Prof Wilder-Smith, the project unites partners from several countries. Can you introduce the consortium members to us and tell us how the cooperation came about?
WS: To achieve the research objectives within these three research areas, we have created 12 work packages where we bring together the expertise, skills and leadership of 14 partners from around the world. The European Commission stipulates that partners have to come from at least 3 European countries, and this specific grant call also asked for partners from developing countries and from small to medium size research enterprises (SME). When preparing for the grant application, I carefully selected relevant partners from around the world who would fit into the overall research theme and bring in the relevant expertise to strengthen the consortium. We have 9 partners from Europe, 4 partners from Asia and 1 partner from South America, including 2 SME. I am fortunate to now be working with a highly talented group of expert. Their skill sets range from epidemiology, economics, laboratory diagnostics, entomology, environmental science, mathematical modelling to clinical. The highlight of the year is when we all come together for our annual consortium meeting!
Prof AbuBakar, your laboratory is participating in the DENGUETOOLS project. Can you tell us a bit about your team and your role as part of the project?
AB: The DENGUETOOLS team at TIDREC (Tropical Infectious Diseases Research and Education Center), University of Malaya, Malaysia, comprises of one principal investigator (PI), four research scientists and three technical support staffs. Our team worked closely with the other partner in the consortium, TwistDx, a UK-based company, to develop, evaluate and fieldtested a simple, rapid and cost effective method for detecting dengue virus in suspected dengue patients using a novel platform technology known as recombinant polymerase amplification (RPA). The team at TIDREC has vast experience in working with arboviruses including dengue virus and our affiliation with the WHO Collaborating Center for Arbovirus Research and Reference (DF/DHF) and the University Malaya Medical Center (UMMC) enabled us to work closely with clinicians and other dengue researchers.
Prof AbuBakar, what motivated your decision to become part of this international research consortium?
AB: DENGUETOOLS fits within our research interest at TIDREC and the opportunity to collaborate with counterparts from the EU is one that we valued. In addition, dengue is a major health concern to Malaysia. We envisaged that findings from the study would have immediate direct benefit to Malaysia and the surrounding dengue endemic regions.
Prof Wilder-Smith, how important is this international cooperation to the success of the project?
WS: The international cooperation is critical to the success of this project; the international nature is in fact the hallmark of our consortium. Because of our international partners, we have field sites in Sri Lanka, Thailand and Malaysia. Our partners from dengue endemic countries also provide insights and advice that we would otherwise not have access to.
Prof Wilder-Smith and Prof AbuBakar, how does the work conducted by the DENGUETOOLS project team benefit the population here in Southeast Asia? Which applications are planned?
WS: In Sri Lanka for example, we were able to enhance an already existing sentinel surveillance in the Colombo district by adding laboratory capacity to diagnose dengue. The Ministry of Health of Sri Lanka was so impressed when he paid us a visit! DengueTools was even featured on national TV. In Thailand, we conducted a large school based study, and hope to provide advice on policy issues to the Thai Ministry of Health in due course.
AB: Dengue affects over 300 million people living in Southeast Asia. Understanding how the disease-spread can be mitigated is of paramount important. Introduction of the RPA detection method for dengue would significantly improve detection of dengue. Rapid diagnosis of dengue would help clinicians differentiate dengue against other potential infections common in the region. Infections such as leptospirosis and chikungunya are common and the early symptoms of these infections are indifferent from dengue. With early diagnosis, dengue patients can be better managed to reduce mortality and immediate public health measures can be taken to limit the spread of the disease.
Prof Wilder-Smith, the project is supported under the Health Cooperation Work Programme of the 7th EU Framework programme. What does the grant application involve? Do you see room for improvement?
WS: The grant application is very time-consuming and complex. I was fortunate to work together with a very capable research manager from Umea University who was able to guide me through the complex requirements of this grant application. Nevertheless, I was probably the most sleep-deprived person by the end of the grant submission, having worked 18-20 hours flat every day in the weeks preceding the submission.
Prof AbuBakar, how would you describe the research collaboration with the European partners?
AB: The collaboration is immensely beneficial to us as it gives us opportunities to participate in an important global research endeavour. Apart from the scientific exposure, we benefitted in learning how to undertake interdisciplinary and multi-institutional international research collaborations.
Prof Wilder-Smith, what advice would you give to European researchers planning to apply for EU research funding?
WS: Firstly, have at least one face to face meeting with all the partners during the submission process in order to polish the research objectives, align the expertise and iron out early on any potential misunderstandings. Secondly, start early!
Dr AbuBakar, and what advice would you give to Southeast Asian researchers seeking closer collaboration with Europe?
AB: Researchers in the Southeast Asia should actively seek participation in the EU supported research consortia. Experience gained from the participation is invaluable and it helped to network with many other international researchers.
Prof Wilder-Smith and Prof AbuBakar, as scientists which goals are you still hoping to achieve?
WS: Dengue vaccine development has come a long way, but we are not there yet. The recently released results of the multi-centre Phase 3 efficacy trial in Asia for the live-attenuated, recombinant dengue fever vaccine (chimeric, with 17D yellow fever virus as the backbone) have yet again shown that an optimal dengue vaccine remains a scientific challenge. Successful roll out of a vaccine that induces high levels of tetravalent protection may hinge on detailed understanding of dengue pathogenesis and immunity. Addressing the gaps in knowledge in these fields must thus be our top priority.
AB: Preventing and reducing deaths due to dengue remains an important goal.
Thank you very much for this interview!