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，土地的转变正在迅速进行，从自然土地转变为农业土地，并沿着农村-城市的连续体。农业面积的扩大和人类住区密度的增加对疾病风险产生了影响。土地使用的变化改变了牲畜、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，非洲的裂谷热就是一个典型的疾病。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感染。裂谷热的大规模流行发生在暴雨引发洪水，从而造成大量蚊子幼虫栖息地的时候。在两次流行之间，RVFV被认为只通过雌性蚊子将病毒传给它们的后代来维持。然而，有新的证据表明，蚊子密度仍然足以在流行病之间传播给牲畜，特别是在城市周边地区和农村地区。在两次流行病之间传播给牲畜会影响局部暴发的频率、病原体在流行病开始时传播的来源，从而在空间和时间上对人类造成风险。在城市周边环境中，人类活动创造了一个马赛克的人类住区，牲畜和病媒栖息地，并以农村或城市地区所没有的方式并列，我们的假设是，城市周边地区和作物种植正在为RVFV的新传播模式创造合适的条件，对暴发风险和控制产生影响。为了解决这一假设，我们将量化蚊子媒介的数量，多样性和喂养行为之间的城市周边和农村地区，草原和作物栖息地，通过在坦桑尼亚北方的实地研究。产生的数据将用于RVFV传播模型中，以及以下数据：i）牲畜密度，运动和周转; ii）媒介物种传播RVFV能力的变化，以确定城市周边环境和作物种植如何影响RVFV的传播途径。我们将通过测试牲畜对RVFV的抗体来验证模型预测的流行病间传播风险最高的地方。由此产生的模型，开发和验证现场数据，将用于模拟流行病，并确定如何传播，爆发规模和人类的风险是由确定的传播途径在城市周边和农村地区爆发之前开始的影响。通过对疫情的模拟，我们将确定最佳干预措施，并调查将这些干预措施针对高风险地区的效果。模拟干预措施将包括牲畜接种疫苗和禁止迁徙，以及使用室内滞留喷洒或经杀虫剂处理的牲畜进行病媒控制。通过利益相关者的参与，我们还将概述一系列生态干预措施，或长期可持续性更高的“障碍”。我们将使用这些模型来确定这些屏障需要在以下方面产生的影响：减少病媒数量，病媒与牲畜之间的接触，或病媒与人类之间的接触，以减少病原体传播和疾病对人类的风险。这些障碍可能包括引进蚊子幼虫捕食者的灌溉系统，使用蚊帐的牲畜，而住房，和人类住房的调整（窗纱，屋檐管）。我们的项目将产生的知识，使坦桑尼亚的决策者制定合理的战略，以监测和控制RVFV，并确定在RVFV的风险领域。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.