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.

黄病毒对全世界人口构成日益严重的问题。在1970年之前，只有9个国家经历过严重的登革热流行;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;现在有86个国家报告了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是具有挑战性的，并且共循环病原体之间的动态可能是导致发病率增加的原因。当人群连续感染不同血清型登革热时，已知抗体依赖性增强（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之间，因为它们的结构几乎相同，这特别令人担忧，因为它们共享相同的载体，埃及伊蚊和A.白纹伊蚊由于气候变化，这些蚊子的栖息地正在扩大，近年来A。白纹伊蚊在加拿大北至南安大略都有发现，埃及人在过去几年中被发现。目前，还没有批准的登革热或寨卡疫苗。对于登革热，这在一定程度上是由于ADE的影响，ADE可能会导致先前没有接触过疫苗的人在随后感染时出现严重的副作用。因此，登革热血清型内以及它们与寨卡之间的动态对于未来的任何预防和控制政策都至关重要。该项目旨在通过使用统计和机制模型阐明考虑ADE的共循环黄病毒的动力学。通过整合加拿大公共卫生保健局（PHAC）目前使用的统计模型，以代表加拿大境内伊蚊的分布，并考虑ADE的登革热和寨卡的机械模型，我们将能够预测考虑到气候变化影响的登革热和寨卡疫情连续和同时爆发的风险变化。该项目将确定携带登革热和寨卡病毒的输入病例和病媒的数量。登革热和/或寨卡病毒需要连续和同时爆发，以及环境和人口变量对未来入侵风险的影响最大。传染病建模需要跨学科的方法，该项目将充分利用Greer博士及其实验室团队提供的各种专家。她每月的实验室小组会议由PHAC的个人参加，这有助于学术界和政策制定者之间的思想和专业知识的交流。将有机会与其他学者合作，如约克大学专门研究共同感染的Hynnan博士和卡尔加里大学生物统计学家Rob Deardon博士。此外，Entomogen Inc.，位于安大略的一家公司负责监测蚊子数量并进行病毒检测。对该小组的访问将增进对蚊子数据收集方式的了解，并阐明报告数据中任何可能的偏差。最后，在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，我们将开发出一个模型，可以用来确定登革热和寨卡病毒在加拿大爆发的风险，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，从而为加拿大未来爆发黄病毒的应急计划提供信息。