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

探索未接触过登革热和寨卡病毒的人群中连续和同时爆发的风险因素

• 批准号: NE/T014687/1
• 负责人: Michael Tildesley
• 金额: $ 1.62万
• 依托单位: University of Warwick
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=NE%2FT014687%2F1
• 关键词: Exploring; Risk; Factors; Sequential; Concurrent

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.

黄病毒给全世界人口带来了日益严重的问题。 1970年之前，只有9个国家经历过严重的登革热疫情；现在登革热在 100 多个国家流行。同样，在 20 世纪 80 年代之前，人类感染寨卡病毒的情况非常罕见。目前已有 86 个国家报告了由蚊子传播的寨卡病毒疫情。预测哪些黄病毒将导致下一次流行病是具有挑战性的，并且共同循环的病原体之间的动态可能是导致发病率增加的原因。众所周知，当人群连续感染不同血清型的登革热时，抗体依赖性增强（ADE）会增加登革热相关疾病的严重程度。据信，这种机制也可能发生在登革热和寨卡病毒之间，因为它们的结构几乎相同，这一点尤其令人担忧，因为它们共享相同的载体：埃及伊蚊和白纹伊蚊。由于气候变化，这些蚊子的栖息地不断扩大，近年来，远至加拿大安大略省南部的北部地区都发现了白纹伊蚊的持续种群，前几年还发现了埃及伊蚊。目前，还没有批准的登革热或寨卡疫苗。对于登革热，这部分是由于 ADE 的影响，如果先前没有接触过 ADE，接种疫苗的个体如果随后被感染，可能会出现严重的副作用。因此，登革热血清型内部以及它们与寨卡病毒之间的动态变化对于未来的预防和控制政策至关重要。该项目旨在通过使用统计和机械模型来阐明考虑 ADE 的共同循环黄病毒的动态。通过将加拿大公共卫生保健机构 (PHAC) 目前使用的代表加拿大各地伊蚊分布的统计模型与考虑到 ADE 的登革热和寨卡病毒机制模型相结合，我们将能够预测顺序和风险的变化。登革热和寨卡病毒同时爆发，考虑到气候变化的影响。该项目将确定连续和同时爆发所需的携带登革热和/或寨卡病毒的输入病例和媒介数量，以及哪些环境和人口变量影响最大在未来入侵风险。对传染病进行建模需要采用跨学科方法，该项目将充分利用格里尔博士和她的实验室小组可以接触到的各种专家。她每月举行的实验室小组会议都有来自 PHAC 的人员参加，这促进了学者和政策制定者之间的思想和专业知识的交流。我们将有机会与其他学者合作，例如约克大学专门研究混合感染的 Heffernan 博士和卡尔加里大学生物统计学家 Rob Deardon 博士。此外，Entomogen Inc. 是一家监测蚊子数量并进行病毒检测的公司，总部位于安大略省。访问该小组将增进对如何收集蚊子数据的理解，并阐明报告数据中任何可能的偏差。最后，2020 年，美国热带医学和卫生学会将在多伦多举行年会，这将提供一个与黄病毒研究专家建立联系的理想机会。在这个项目结束时，我们将开发一个模型，可以用于用于确定加拿大爆发登革热和寨卡病毒的风险，并考虑到未来的气候变化。该模型的输出将直接传达给我们在圭尔夫大学和 PHAC 的合作者，从而为未来加拿大黄病毒爆发的应急计划提供信息。