Identifying inter-epizootic transmission routes of Rift Valley fever virus in Tanzania to inform targeted control strategies for outbreak response

在全球范围内，土地正在沿着城乡连续体迅速从自然向农业转变。农业地区的扩大和人类住区密度的增加对疾病风险产生了影响。土地利用变化改变了家畜、野生动物和昆虫种群的生存条件，也改变了它们传播的病原体，为人类接触动物病原体创造了新的机会。非洲的裂谷热是一种典型疾病。致病性病毒（RVFV）主要通过蚊子在牛、绵羊和山羊之间传播。人类可以通过接触受感染的动物或被传染性蚊子叮咬而被感染。当暴雨引起洪水，造成大面积的蚊子幼虫栖息地时，就会发生裂谷热大流行。在两次流行之间，裂谷热病毒被认为仅通过雌蚊将病毒传给后代而得以维持。然而，越来越多的证据表明，在两次流行病之间，特别是在城郊和农村地区，蚊子的密度始终足以传播给牲畜。在流行病之间向牲畜传播会影响局部暴发的频率、流行病开始时病原体的传播来源，从而在空间和时间上给人类带来风险。在城市周边环境中，人类活动创造了人类住区、牲畜和病媒生境的马赛克，并置在一起，这在农村或城市地区是不会发生的。我们的假设是，半城市化和作物种植正在为裂谷热病毒传播的新模式创造合适的条件，这对爆发风险和控制有影响。为了解决这一假设，我们将通过在坦桑尼亚北部的实地研究，量化蚊子媒介的数量、多样性和摄食行为在城郊和农村地区以及在草原和作物栖息地之间的差异。所产生的数据将用于裂谷热病毒传播模型，以及以下数据：1)牲畜密度、流动和周转；ii)媒介物种传播裂谷热病毒能力的变化，以确定城市周边环境和作物种植如何影响裂谷热病毒的传播途径。我们将通过检测牲畜的裂谷热病毒抗体来验证模型预测的疫区间传播风险最高的地区。利用实地数据开发和验证的由此模型将用于模拟流行病，并确定疫情开始前城郊和农村地区已确定的传播途径如何影响传播、疫情规模和对人类的风险。通过对疫情的模拟，我们将确定最佳干预措施，并调查针对高风险地区采取这些干预措施的效果。模拟干预措施将包括牲畜疫苗接种和禁止移动，以及使用室内残留喷洒或对牲畜进行杀虫剂处理的病媒控制。通过利益相关者的参与，我们还将概述一份生态干预措施的清单，或在长期内可能更具可持续性的“障碍”。我们将使用这些模型来确定这些屏障需要对以下两方面产生的影响：减少病媒数量，减少病媒与牲畜之间的接触，或减少病媒与人类之间的接触，以减少病原体传播和对人类的疾病风险。这些障碍可能包括在灌溉系统中引入蚊子幼虫捕食者，在饲养牲畜时使用蚊帐，以及人类住房调整（窗纱、屋檐管）。我们的项目将产生知识，使坦桑尼亚的决策者能够制定合理的战略来监测和控制裂谷热病毒，并确定存在裂谷热病毒风险的地区。我们的全系统方法将为人类和牲畜的其他蚊媒病原体提供一个框架。

Globally, land transformation is proceeding rapidly from natural to agricultural and along a rural-urban continuum. The expansion of agricultural areas and increasing density of human settlements have consequences for disease risk. Land use change alters conditions for livestock, wild animals, and insect populations in addition to the pathogens they transmit, creating new opportunities for exposure of people to animal pathogens.One exemplar disease is Rift valley fever (RVF) in Africa. The causative virus (RVFV) is transmitted primarily between cattle, sheep, and goats by mosquitoes. Humans can become infected either by handling an infected animal or from the bite of an infectious mosquito. Large epidemics of RVF occur when heavy rains cause floods leading to the creation of extensive mosquito larval habitats. Between epidemics, RVFV was thought to be maintained only by female mosquitoes passing virus to their offspring. However, there is emerging evidence that mosquito density is continually sufficient for transmission to livestock between epidemics, importantly in peri-urban, as well as rural areas. Transmission to livestock between epidemics has consequences for the frequency of localised outbreaks, the sources of pathogen spread at the start of an epidemic, and consequently risk to humans in space and time. In peri-urban settings, human activities create a mosaic of human settlements, livestock and vector habitats that are juxtaposed in ways that do not occur in rural or urban locations.Our hypothesis is that peri-urbanisation and crop cultivation is creating suitable conditions for new patterns of RVFV transmission, with implications for outbreak risk and control. To address this hypothesis, we will quantify how the numbers, diversity and feeding behaviour of mosquito vectors varies between peri-urban and rural areas, and between grassland and crop habitats, through field studies in northern Tanzania. The data produced will be used within models of RVFV transmission, alongside data on: i) livestock density, movement and turnover; and ii) variation in vectors species' ability to transmit RVFV, to determine how peri-urban settings and crop cultivation are affecting transmission routes for RVFV.We will validate model predictions of where inter-epidemic transmission risk is highest through testing livestock for antibodies against RVFV. The resulting model, developed and validated with field data, will be used to simulate epidemics and determine how spread, outbreak size and risk to humans is influenced by the identified transmission routes in peri-urban and rural areas prior to the start of the outbreak. Through simulations of outbreaks we will then identify optimal interventions and investigate the effect of targeting these interventions to high risk areas. Simulated interventions will include livestock vaccination and movement bans in addition to vector control using indoor residual spraying or insecticide-treated livestock.Through stakeholder engagement, we will also outline a list of ecological interventions, or 'barriers' that may be more sustainable in the long-term. We will use the models to establish the effect that these barriers would need to have on either: reducing vector numbers, contacts between vectors and livestock, or contacts between vectors and humans to reduce pathogen transmission and disease risk to humans. These barriers may include introduction of mosquito larval predators in irrigation systems, the use of nets for livestock while housed, and human housing adjustments (window screens, eave tubes).Our project will generate knowledge to enable policy makers in Tanzania to develop rational strategies to monitor and control RVFV and identify areas at risk of RVFV. Our whole-system approach will provide a framework for other mosquito-borne pathogens of humans and livestock.