Understanding, forecasting, and mitigating zoonotic mosquito-borne viral disease in the U.K.

在英国，有效监测和控制病媒传播疾病（VBD）需要一种综合方法。这个多学科项目结合了从医学昆虫学、病毒学到计算建模的各种专业知识，以调查与英国蚊媒疾病的理解、预测和缓解有关的领域。通过在多个机构之间建立伙伴关系，我们将解决以下问题：(i)本地传播最有可能发生的方式和地点；（ii）如何使行之有效的病媒控制战略适应联合王国的情况；（iii）研究降低风险的新方法。我们的合作涵盖学术、工业和政府组织，提供解决这些问题所需的独特能力和专业知识。第一个工作包（由Jones博士和Lord博士[早期职业研究员- ECR]领导）将通过实地研究和计算模型确定影响西尼罗河病毒传播可能性的因素。这包括不同栖息地的蚊子群落组成，这些栖息地之间的移动（Chapman博士），以及蚊子和鸟类群落是否具有维持传播的能力（STFC Hartree的Mason博士）。然后将使用西尼罗河病毒传播模型来确定在这些社区背景下控制策略的有效性。关注这些精细尺度的动态是很重要的，因为这种粒度在大规模的国家调查中可能被忽视，这里提出的问题将告知这些调查的有用性和可靠性。在工作包二（由Longbottom博士[ECR]和Lord博士[ECR]领导）中，我们将绘制潜在西尼罗河病毒载体的物种分布图。以前的估计是十多年前的，后来又有了更多的当代空间数据。此外，本工作包将探索不同空间尺度的模型预测和准确性，并研究在政策和实施中使用不同尺度的产出。该工作包的要素将利用UKHSA的伙伴关系来促进利益相关者的讨论和研究吸收。WP1和w2将以现有的西尼罗河病毒风险评估为基础，通过提供精细数据和关注蚊子群落而不是单个物种，为政府政策提供信息。在最后的工作包中，我们将探索适用于英国的新颖和经过验证的病媒控制策略。在A部分（由PI Hughes博士领导），我们将与Verily Life Sciences和Walker博士（华威大学）合作，制定基于沃尔巴克氏体的库蚊控制策略。我们将引入一种新的沃尔巴克氏体菌株进入鼠库蚊背景，并研究其改变蚊子繁殖和抑制蚊子种群的能力。此外，我们将检查沃尔巴克氏体阻断英国相关病原体的能力，包括西尼罗河病毒和Usutu病毒（USUV）。这项工作的结果将构成未来控制方法的基础，我们与Verily Life Sciences的合作使我们能够迅速将这项研究转化为英国的应用控制方法。在本最终工作包的B部分（由RCo-I Casas-Sanchez博士领导）中，我们将研究糖基化途径如何在体外和体内影响西尼罗河病毒和USUV等虫媒病毒。阻断病毒而不是针对蚊子的能力使病媒控制方法能够跨蚊子种类发挥作用，鉴于多物种群落在传播中的作用（在WP1中确定），这是一个关键因素。我们有ecr作为工作包，我们承诺在这个项目中指导这些研究人员，更广泛地说，指导他们独立。在我们朝着降低英国传播风险的目标前进的过程中，我们的OneHealth方法和对VBD的理解、预测和缓解范围将为未来的规划和研究提供关键数据。

Effective surveillance and control of vector-borne disease (VBD) in the UK requires an integrative approach. This multi-disciplinary project combines diverse expertise from medical entomology, virology to computational modelling to investigate areas related to the understanding, forecasting, and mitigation of mosquito-borne disease in the UK. By forging partnerships across several institutions, we will address questions including (i) how and where local transmission will most likely occur; (ii) how can proven vector control strategies be adapted to a UK context; and (iii) and investigate novel approaches to mitigate risk. Our collaboration spans academic, industry, and governmental organisations, providing the unique capacity and expertise needed to address these questions. The first work package (WP) (led by Co-I Dr Jones and Co-I Dr Lord [Early Career Researcher - ECR]) will determine factors that influence the potential for transmission of WNV over a fine scale using field studies and computational modelling. This includes mosquito community composition in different habitats, movement between these habitats (Dr Chapman), and whether mosquito and bird communities have the capacity to sustain transmission (Dr Mason, STFC Hartree). Models of WNV transmission will then be used to determine the efficacy of control strategies in the context of these communities. Focusing on these fine-scale dynamics is important as this granularity may be overlooked in broad scale national surveys, and the questions raised here will inform on the usefulness and reliability of these surveys. In work package two (led by RCo-I Dr Longbottom [ECR] and Co-I Dr Lord [ECR]), we will produce species distribution maps for potential WNV vectors. Previous estimates are over 10 years old and additional contemporary spatial data has since become available. Additionally, this work package will explore different spatial scales for model prediction and accuracy and investigate the use of outputs of varying scales in policy and implementation. Elements of this work package will leverage partnerships at UKHSA to facilitate stakeholder discussion and research uptake. Collectively WP1 and 2 will build on existing WNV risk assessments to inform government policy, by providing fine-scale data and a focus on communities of mosquitoes rather than individual species. In the final work package, we will explore novel and proven vector control strategies for their applicability to the UK. In part A (led by PI Dr Hughes), we will partner with Verily Life Sciences and Dr Walker (University of Warwick) to develop a Wolbachia-based control strategy for Culex mosquitoes. We will introgress a novel Wolbachia strain into the Culex molestus background and examine its capacity to alter mosquito reproduction and suppress mosquito populations. Additionally, we will examine the ability of Wolbachia to block pathogens relevant to the UK including WNV and Usutu virus (USUV). Results from this work will form the basis of future control approaches and our partnership with Verily Life Sciences uniquely places us to rapidly transition this research into an applied control approach in the UK. In part B of this final work package (led by RCo-I Dr Casas-Sanchez), we will examine how glycosylation pathways affect arboviruses such as WNV and USUV in vitro and in vivo. The ability to block the virus, rather than target the mosquito enables vector control approaches that can work across mosquito species, a critical factor given the role of multi-species communities in transmission (identified in WP1). We have ECRs as work packages leads and we commit to mentoring these researchers in this project and more generally towards their independence. Together, our OneHealth approach and spectrum of understanding, forecasting, and mitigation of VBD will provide critical data for future planning and research as we move towards the aim of reducing the risk of transmission in the UK.