Triple-D Targets: The UK-Philippines Dengue Diagnostic and Drug Targets Research Consortium

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Dengue is the most important mosquito-borne disease of humans and is constantly spread in the Philippines, which has the 4th largest dengue disease burden of all Southeast Asian countries. Infection with dengue virus (DENV) causes a spectrum of clinical illnesses, ranging from dengue fever, a debilitating but self-limited condition to the more severe and potentially fatal dengue haemorrhagic fever. Dengue has a major impact on the health and economy of the Philippines as epidemics occur every 2-3 years. Over 500 000 confirmed cases occurred from 2008 - 2012 with > 3000 deaths. Although most dengue cases could be managed at home, the lack of a diagnostic test to predict those individuals who progress from mild to severe disease forces patients and healthcare providers to seek hospital admissions for "safety purposes", saturating an already overwhelmed healthcare system.The overall objective of this collaboration between academic institutes in the Philippines and the UK is to create a state-of-the-art infrastructure that that will allow better diagnosis of patients who develop severe disease after infection with DENV. In order to achieve our objective we will establish a very well characterised biobank of patient samples, collected from patients with different dengue disease outcomes as the disease progresses. We will use sophisticated methods to look at the strains of DENV that are circulating in the Philippines and also identify any changes in patient RNA or proteins which we can detect in blood that might be linked to serious disease associated with DENV infection. The methods will be both high throughput and very sensitive so that even changes in the abundance of low-level transcripts or proteins will be detected. We will also be able to detect the frequency of minor changes in the virus and investigate whether these may be linked to disease. This technology will be transferred to the Philippines so that they can monitor the virus infections, which are circulating in the country. The results will produce large amounts of data that will be brought together using computational methods, either available or be developed by the Filipino and UK groups. The UK partners have particular experience with the bioinformatics tools needed and will provide these to their Filipino counterparts. These skills and those for detecting mutations in DENV will be transferred to the Philippines through short-term scientific exchange visits, regular real-time cyber-mentoring sessions as well as joint workshops throughout the project. Computational analysis of the datasets will allow us to identify biomarkers in patients, which will be validated with additional samples. After validation, any biomarkers can then be used to develop diagnostic tests to predict those individuals at risk of progressing to severe disease and to monitor DENV variability and detect other infections associated with febrile disease. We will also identify cell pathways in infected patients which can be targeted with existing drugs, potentially to prevent severe disease. Overall, the project will significantly support the building of research capacity in the Philippines. Critically, the training and technology transfer provided by the UK partners will help to establish an adaptable technological framework that is also relevant to many other infectious disease areas in the Philippines.