Dengue

Dengue is the most important mosquito-borne viral infection of humans. It represents a major problem for public health services around the world, with recent estimates indicating that 390 million infections occur each year, of which almost 100 million are symptomatic. Infection can be caused by any one of four closely related dengue viral (DENV) serotypes, transmitted between people by Aedes mosquitoes. The disease is endemic across much of Asia and Latin America, and the global footprint is expanding rapidly in parallel with the dispersal of efficient mosquito vectors across tropical and subtropical regions of the world.

Although most DENV infections are asymptomatic, a wide variety of clinical manifestations may occur, ranging from mild febrile illness to severe and fatal disease. In most cases these symptoms resolve within one week, however a small proportion of patients develop complications that may include bleeding, organ dysfunction and a capillary leak syndrome that progresses to hypovolaemic shock in severe cases, i.e. dengue shock syndrome. Currently no antivirals or other therapeutic agents have been shown to be effective and careful supportive care, with a particular focus on judicious fluid management, remains the cornerstone of good case-management. Deployment of effective vector control strategies remains an important approach in global disease prevention efforts.

Dengue Group

The Dengue Group is one of the largest research groups at OUCRU, with 28 staff including clinicians, scientists, post-doctoral and PhD students as well as research assistants and study nurses. The group has a strong international focus with expanding collaborative research networks across Southeast Asia, as well as in the UK, Australia and the USA. The group’s primary objectives are to improve diagnosis and management of dengue at a global level, and to facilitate/enhance disease prevention strategies. We have established a coordinated program of clinical research supported by a platform of enabling science focused on pathogenesis research, physiology studies, epidemiology and clinical entomology studies.

Major achievements in last 5 years

  • World leadership in therapeutic intervention trials for dengue.
  • Development of an international standard insectary in HCMC, facilitating a unique body of work around human to mosquito transmission in a dengue-endemic area
  • Completed a large multi-country study on early diagnosis and risk prediction, recruited >7000 patients across 8 countries (IDAMS) – data being used to update the WHO and IMCI guidelines.
  • Important contributions to 3 WHO dengue expert working groups/guidelines committees.
  • Leadership within the world mosquito program resulting in phased release of Wolbachia infected Aedes aegypti mosquitoes in Vietnam and other countries in Asia and Latin America.
  • Development of  strong  collaborative  links  with  a  number  of institutions  including  Imperial College London, Kings College London, University of Glasgow, University of California Berkley, DUKE-NUS Singapore, LKCM Singapore, and University of Queensland, as well as others..
  • More than 80 papers on dengue in major international journals, and >10 book chapters including NEJM, Nature, Nature Genetics, PNAS, CID etc.
  • Major external funding awards to support the IDAMS consortium (6M Euro, EU FP7 grant), and the World Mosquito program (13.6M AUD), plus >2M AUD and 1M USD in smaller grants from the Wellcome Trust, NHMRC, Sir Halley Stewart Trust and the WHO.
  • 4 WT or WT/Joint Fellowship awards to group members:
  • Successful completion of 12 PhDs (Open University, LSHTM, Imperial College London)

Current Research themes

Intervention studies
We continue to lead the field in clinical trials of novel host-directed therapeutics in partnership with the Hospital of Tropical Diseases.

Dengue biomedical Innovations
In collaboration the centre for bio-inspired technology, Imperial College London, we are developing a first-of-its-kind, non-invasive, wearable sensor tailored for real-time clinical assessment of dengue patients. In addition, through engineering collaborators at Kings College London, we are developing new imaging technology to fully automate cardiac and lung ultrasound measurements.

Dengue pathogenesis studies in high risk groups
A matched cohort study is ongoing at HTD to investigate the association of dengue severity in overweight/obese patients. Other high-risk groups that have been studied include pregnant women and we plan to start a study in elderly patients in dengue.

Vascular studies
One of the group’s main aims is to try to understand the reasons why some people get severe disease and to work out what the pathological processes are that cause these severe manifestations. One area of special interest focuses on identifying structural and/or functional changes in the microcirculation, so that we can understand how dengue infection causes blood vessels to become ‘leaky’, abnormalities that contribute to bleeding.

Fluid management studies in dengue shock syndrome
A prospective study in PICU is ongoing, investigating novel hemodynamic monitoring strategies to assess fluid responsiveness in Vietnamese children with DSS. This work will lead onto future studies using these novel devices for targeted fluid intervention trials.

Viral-Mosquito studies
These studies comprise a number of sub-projects investigating the susceptibility of mosquitoes to DENV infection under various environmental conditions and manipulated treatment. The capacity of Wolbachia to block virus infection has been a major theme of this work, with studies comparing multiple Wolbachia strains, evolution of dengue in the presence of Wolbachia, and assessing Wolbachia to block virus in vertical transmission also.

Arbovirus surveillance in Ho Chi Minh City
This community-based arbovirus surveillance study is a collaboration between PMC, HTD and OUCRU, to characterise the prevalence and distribution of arbovirus infections in mosquitoes in Ho Chi Minh City.

Dengue research locations in Viet Nam

  • Hospital for Tropical Diseases, Ho Chi Minh City
  • National Hospital for Tropical Diseases, Hanoi
  • Children Hospitals No.1 and No. 2, Ho Chi Minh City
  • Huong Vuong Hospital, Ho Chi Minh City
  • Tien Giang Hospital
  • Dong Thap Hospital
  • Binh Duong Hospital
  • Dong Nai Paediatric Hospital
  • Long An Hospital
  • Tri Nguyen Island (Eliminate Dengue Wolbachia projects)

Dengue collaborations/partnerships

  • Imperial College, London, UK
  • London School of Hygiene and Tropical Medicine, UK
  • Kings College London, UK
  • University of Glasgow, UK
  • University of Bristol, UK
  • University of California, Berkeley
  • University of Queensland, Australia
  • Monash University, Australia
  • World Mosquito Program (https://www.worldmosquitoprogram.org)
  • IDAMS (http://www.idams.eu)
  • Heidelberg University Hospital, Germany
  • The Special Programme for Research and Training in Tropical Diseases of the World Health Organization (WHO/TDR), Geneva, Switzerland
  • Pedro Kouri Tropical Medicine Institute, Havana, Cuba
  • DUKE-NUS, Singapore
  • LKCM, Singapore
  • Singapore Immunology Network