Immunology, molecular biology and control of flaviviruses (Dengue and Zika)

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The flaviviruses Dengue and Zika are endemic to much of the tropical and sub-tropical areas of the world. Spread by Aedes mosquitos, one estimate indicates 390 million dengue infections per year, of which 96 million manifest clinically (with any severity of disease). Another study, of the prevalence of dengue, estimates that 3.9 billion people, in 128 countries, are at risk of infection with dengue viruses. Although Zika virus was first identified in the 1950s it was an outbreak in 2015 in South America which brought it to global attention, during this outbreak there was a marked increase in cases of children born with birth defects. The efficiency of Dengue disease transmission can be seen in places such as Singapore, where very low numbers of these mosquitos can be found (Aedes premises index of less than 1% and virtually no infected mosquitos identified) and yet incidence rates are high (typically more than 200 cases notified per year per 100,000 residents) and in 2013 there were more than 23,000 hospitalizations (for a population of 5.5 million).Despite Dengue virus being one of the most studied viruses, some critical components of the epidemiology dynamics are unknown. For example; the mosquito typically only flies 150m in its life time of two weeks (and two feeding periods) and dengue infected patients are typically only contagious to the mosquito for 3 to 6 days (during the fever stage). Extensive recent research has concentrated on explaining mosquito numbers in relation to weather variables and correlating this to disease incidence, but further work integrating this knowledge with viral molecular epidemiology is likely to reveal more precise details of how the disease spreads from person to person.Next-generation sequencing technologies can allow phylogenetic analysis of viral outbreaks, can reveal the path of the outbreak and additionally can detect mutations that may be associated with new disease phenotypes or affect molecular diagnostics. These can be used to therefore infer transmission dynamics. This project will utilize a comprehensively monitored cohort from Vietnam to follow real time dengue outbreaks, household clusters of cases and obtain blood samples that will permit molecular typing, together with serological data. Taken together, this data will enable mathematical model testing and refinement; while also initiating a field site that could later be used for interventions.I will initially be focussing on developing and using molecular detection techniques to diagnose and sequence the virus. Data generated by this will then be used to infer routes of transmission as well as how the virus responds to immunological pressures.