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，但这种空间和时间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，我们将梳理出环境、生理和微生物因素对人类蜱传立克次体感染风险的影响。这项工作的模式蜱传疾病（TBD）系统的目标是美国的斑点钝眼蜱和帕克立克次体，以及非洲的非洲钝眼蜱和非洲立克次体; parkeri和R.非洲斑疹热是斑点热群立克次体，已知会引起人类疾病。R. parkeri在A. maculatum在这个蜱的迅速扩大的范围的前沿，和R。Africae是南部非洲的地方病，研究报道很少。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病原体暴露创造新机会的地方。美国和非洲的Amblyomma/立克次体系统将比较研究同一现象的不同方面：在媒介分布的不同部分蜱中病原体流行的时空异质性。在这两个系统中，我们将把我们的研究集中在A的范围的边缘和核心的网站。maculatum和A.希伯来文。该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来为数学模型提供信息。基于实验的传输率的经验确定将提供重要的生命史信息，并确定模型结构。宿主蜱和立克次体的分子研究将产生蜱运动和细菌菌株变异和蜱微生物群落的种群动态信息。田间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的流行梯度和遗传结构的贡献。最后，所有这些信息将被综合在数学模型中，以衡量这些TBD系统中不同驱动因素和TBD风险的相对重要性。病媒和病媒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，可以使用比较方法探索TBD发生的理论背景，包括宿主社区的稀释效应，病原体流行和病媒丰度的核心边缘效应，以及起源中心对病媒和病原体种群遗传结构的影响。拟议的工作将开发先进的蜱传立克次体感染动态数学模型，这些模型将通过传播研究，微生物组分析，群体遗传学，GIS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，扩大蜱虫范围和改变土地利用的领域。

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.