Exploring Risk Factors for Sequential and Concurrent Dengue and Zika Outbreaks in a Naïve Population

Flaviviruses pose an ever increasing problem for the worldwide population. Before 1970 only 9 countries had experienced severe dengue epidemics; now dengue is endemic in over 100 countries. Similarly, before the 1980s human infection from Zika was a very rare occurrence; now 86 countries have reported mosquito-transmitted Zika outbreaks. It is challenging to predict which flaviviruses will result in the next epidemic and the dynamics between co-circulating pathogens may be responsible for increased morbidity. Antibody dependent enhancement (ADE) is known to increase the severity of dengue-related illnesses when a population is infected with different serotypes of dengue consecutively. It is believed that this mechanism may also occur between dengue and Zika owing to their near identical structures, which is particularly concerning as they share the same vectors, Aedes aegypti and A. albopictus. As a result of climate change, the habitat of these mosquitoes is expanding and in recent years persistent populations of A. albopictus have been found as far north as Southern Ontario in Canada with A. aegypti being found in previous years. Currently, there is no approved vaccine for dengue or Zika. For dengue this is in part due to the effects of ADE, which could see vaccinated individuals with no prior exposure experiencing severe side effects should they be subsequently infected. Therefore, the dynamics within dengue serotypes and between them and Zika is crucially important for any future prevention and control policies.

This project aims to elucidate the dynamics of co-circulating flaviviruses considering ADE through the use of statistical and mechanistic models. By integrating the statistical models used currently by the Public Health Care Agency of Canada (PHAC) to represent the distribution of Aedes across Canada with a mechanistic model for dengue and Zika considering ADE, we will be able to forecast the change in risk for sequential and concurrent dengue and Zika outbreaks that take into account the effect of climate change.This project will determine the number of imported cases and vectors carrying dengue and/or Zika required for sequential and concurrent outbreaks to occur and which environmental and demographic variables have the biggest impact upon future invasion risk.

Modelling infectious diseases requires an interdisciplinary approach and this project will take full advantage of the wide variety of specialists accessible through Dr Greer and her lab group. Her monthly lab group meetings are attended by individuals from PHAC which facilitates an exchange of ideas and expertise between academics and policy makers. There will be opportunities to collaborate with other academics such as Dr Heffernan who specialises in co-infection, from York University, and Dr Rob Deardon, a biostatistician at the University of Calgary. Furthermore Entomogen Inc., a company which monitors the mosquito population and carries out viral testing, is based in Ontario. Visits to this group will improve understanding of how mosquito data are gathered and elucidate any possible biases in reported data. Finally, in 2020 the American Society for Tropical Medicine and Hygiene are holding their annual conference in Toronto, which will provide an ideal opportunity to network with experts in the flavivirus research.

At the conclusion of this project we will have developed a model that can be utilised to establish the risk of outbreaks of dengue fever and Zika occurring in Canada that takes into account future climate change. The outputs of this model will be communicated directly to our collaborators at the University of Guelph and PHAC, thus informing contingency planning for outbreaks of flaviviruses in Canada in the future.