Spatial eco-epidemiology of tick-borne rickettisal pathogens

立克次体蜱传病原体在其蜱媒中表现出广泛的流行，但这种时空异质性的驱动因素尚不清楚。通过对两个平行系统的多学科研究，我们将梳理环境、生理和微生物因素对人类蜱传立克次体感染风险的影响。这项工作的模型蜱传疾病（TBD）系统针对的是美国的斑状浅螺旋体和白氏立克次体，以及非洲的中华浅螺旋体和非洲立克次体；柏氏R.和非洲R.都属于立克次体斑疹热群，已知会引起人类疾病。在这种蜱迅速扩大的范围的前沿，在斑纹蜱中发现了帕克瑞氏蜱的高流行率，而非洲蜱在非洲南部的地方性研究很少报道。TBD风险发生在影响病原体-蜱-宿主相互作用或蜱生活史和行为的环境条件为人类接触病原体创造了新机会的地方。美国和非洲弱视/立克次体系统将比较检查同一现象的不同方面：媒介分布不同地区蜱中病原体流行的时空异质性。在这两个系统中，我们将把研究重点放在斑纹蒿和希伯来蒿分布范围的边缘和核心位置。本提案详细介绍了一个全面的方法来解决这个问题，使用一套有针对性的研究，以告知数学模型。基于实验室的传输率的经验测定将提供重要的生活史信息并确定模型结构。寄主蜱和立克次体的分子研究将为蜱的运动和种群动态、细菌菌株变异和蜱微生物群提供信息。野外生态学研究将检查蜱和立克次体病原体的自然时空变异性，以及假定的宿主群落组成的影响。地理空间分析将揭示环境因素对蜱和立克次体流行梯度和遗传结构的影响。最后，所有这些信息将在数学模型中综合，以衡量这些TBD系统中不同驱动因素的相对重要性以及TBD风险的总体重要性。疾病媒介和媒介传播病原体发生的空间异质性对TBD风险至关重要，本研究为我们提供了独特的机会，可以使用比较方法在许多理论背景下探索TBD的发生，包括宿主群落的稀释效应、对病原体流行和媒介丰度的核心边缘效应、以及起源中心对媒介和病原体种群遗传结构的影响。拟议的工作将开发蜱传立克次体感染动力学的先进数学模型，该模型将通过传播研究、微生物组分析、群体遗传学、地理信息系统和遥感提供信息，并将提供一个框架，通过该框架可以对其他病原体进行类似的研究。最终，这些努力将有助于风险评估、控制措施和教育工作，扩大蜱虫的范围和改变土地利用的区域。

Rickettsial tick-borne pathogens exhibit a wide range of prevalence in their tick vectors, yet the drivers of this spatial and temporal heterogeneity are unknown. Through a multidisciplinary study of two parallel systems, we will tease apart influences of environmental, physiological, and microbial factors on human risk of tick-borne rickettsial infection. The model tick-borne disease (TBD) systems for this work target Amblyomma maculatum and Rickettsia parkeri in the US, and Amblyomma hebraeum and Rickettsia africae in Africa; both R. parkeri and R. africae are spotted fever group Rickettsia, known to cause disease in humans. R. parkeri has been found at high prevalence in A. maculatum at the leading edge of this tick's rapidly expanding range, and R. africae is endemic in southern Africa with few reported studies. TBD risk is occurring in locations where environmental conditions that affect pathogen-tick-host interactions or tick life history and behavior create new opportunities for pathogen exposure in humans. The US and African Amblyomma/Rickettsia systems will comparatively examine different aspects of the same phenomenon: the spatiotemporal heterogeneity in pathogen prevalence in ticks in different parts of the vector's distribution. In both systems, we will focus our study at sites at the edge and core of the ranges of A. maculatum and A. hebraeum. This proposal details a comprehensive approach to this question using a suite of targeted studies to inform mathematical models. Laboratory-based empirical determination of transmission rates will provide important life history information and determine model structure. Molecular studies of both host ticks and rickettsia will generate information on tick movements and population dynamics on bacterial strain variation and tick microbiomes. Field ecology studies will examine natural temporal and spatial variability of ticks and rickettsial pathogens, as well as influences of putative host community composition. Geospatial analyses will reveal the contribution of environmental factors to prevalence gradients and genetic structuring of ticks and rickettsia. Finally, all of this information will be synthesized in mathematical models to weigh relative importance of different drivers in these TBD systems and of TBD risk in general. Spatial heterogeneity in occurrence of disease vectors and vector-borne pathogens is fundamentally important to TBD risk, and this study gives us the unique opportunity to use a comparative approach to explore TBD occurrence in a number of theoretical contexts including dilution effects of host communities, core-margin effects on pathogen prevalence and vector abundance, and center of origin impacts on vector and pathogen population genetic structure. The proposed work will develop advanced mathematical models of tick-borne rickettsial infection dynamics that will be informed by transmission studies, microbiome analyses, population genetics, GIS, and remote sensing, and will provide a framework by which similar studies may be performed for other pathogens. Ultimately, these efforts will aid in risk assessment, control measures, and education efforts, in expanding tick ranges and areas of changing land use.