Spatial eco-epidemiology of tick-borne rickettisal pathogens

立克次体硬质媒介病原体的流行范围很广，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硬体传播立克次体感染风险的影响。这项工作的模式壁虱传播疾病(TBD)系统的目标是美国的斑点钝圆线虫和帕氏立克次体，以及非洲的赫布卢玛念珠菌和非洲立克次体；帕氏杆菌和非洲立克次体都是斑点热群立克次体，已知会在人类中引起疾病。帕氏锥虫在斑纹伊蚊中发现了很高的流行率，在这一快速扩大的范围的前沿，非洲锥虫在南部非洲是地方性的，几乎没有报道的研究。待定疾病风险发生在影响病原体-扁虱-宿主相互作用的环境条件或扁虱生活史和行为为人类接触病原体创造新机会的地方。美国和非洲的Amblyomma/Rickettsia系统将对同一现象的不同方面进行比较研究：病原体在媒介分布的不同部分在扁虱中流行的时空异质性。在这两个系统中，我们将重点研究斑点木兰和黑线木兰山脉的边缘和核心位置。这项提案详细说明了这个问题的综合方法，使用一套有针对性的研究来为数学模型提供信息。基于实验室的传播率的经验确定将提供重要的生活史信息并确定模型结构。对寄主硬体和立克次体的分子研究将产生有关硬体移动的信息，以及细菌菌株变异和硬体微生物群的种群动态信息。现场生态学研究将检查硬蜱和立克次体病原体的自然时空变异性，以及假定宿主群落组成的影响。地理空间分析将揭示环境因素对扁虱和立克次体流行梯度和遗传结构的影响。最后，所有这些信息将被综合在数学模型中，以权衡不同驱动因素在这些待定发展系统中的相对重要性和总体待定发展风险。病媒和病媒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，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，对病原体流行率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。这项拟议的工作将开发由硬质立克次体传播的立克次体感染动态的高级数学模型，这些模型将得到传播研究、微生物组分析、种群遗传学、地理信息系统和遥感的信息，并将提供一个框架，可用于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、控制措施和教育努力，扩大滴答范围和土地使用变化的领域。

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.