Transmission and evolution of a persistent pathogen: anthrax infection dynamics comparing two natural systems

炭疽病是一种全球性的野生动物、牲畜和人类疾病。 由于对病原体生态学的地理差异以及疾病暴发的模式缺乏了解，对炭疽爆发的成功预测和反应受到限制。 该项目将调查宿主、病原体和环境的作用，以了解病原体-宿主相互作用如何演变以及导致两个研究地区之间炭疽病发生差异的原因。这两个地区都在南部非洲，有着非常不同的炭疽爆发动态，这代表了全世界炭疽系统的变化。在纳米比亚的埃托沙国家公园，每年雨季都会发生影响放牧斑马的小规模疫情。相比之下，在南非克鲁格国家公园，影响食草捻的较大爆发发生在旱季，大约有十年的规模。该项目建立在每个公园疾病和种群动态的详细记录以及存档的病原体样本的基础上，并将涉及新的数据收集和分析以及数学建模，以了解这些不同的动态。教育、培训、科学和公众宣传是这项研究的重要组成部分。来自不同背景的博士后研究人员和本科生和研究生将接受现场，实验室和定量技术的培训，强调尖端的基因组学，统计和动态建模方法。炭疽的病原体（炭疽杆菌），经常被援引为高毒性和延长环境生存进化的教科书例子。该项目将连接宿主内，宿主间和环境中的过程，以了解相互冲突的选择压力如何影响病原体多样性，宿主抗性，疾病发生率，以及最终这些过程如何驱动宿主-病原体共同进化。这个合作研究小组将比较两个野生动物系统中的炭疽动态，整合长期实地研究，宿主和病原体基因组学，微生物学以及统计和动态建模。该项目解决了三个相关的问题：（1）病原体多样性如何影响病原体传播和毒力之间的权衡？(2)宿主多样性如何影响病原体传播和毒力之间的权衡？以及（3）病毒规模的传播和宿主移动模式如何影响毒力-传播权衡和宿主-病原体种群动态？研究人员将把B的变异性联系起来。炭疽菌基因组到表型（即，病原体在环境中的存活、对宿主的毒力以及跨宿主和地理范围的传播）。研究人员将在病原体介导的选择下，在两种主要宿主物种，平原斑马（Equus quagga）和大捻（Tragelaphus strepsiceros）中识别宿主基因。研究人员将建立流行病学和种群动态的生物学水平模型，包括宿主运动，传播途径，病原体毒力和宿主抗性。 最后，研究人员将建立模型，预测炭疽在生态系统中的传播动态。从更广泛的意义上说，这项研究将促进预测工具的发展，以更好地管理公共卫生和相关政策的复杂，多宿主的人畜共患病，如炭疽。这一奖项反映了NSF的法定使命，并已被认为是值得通过评估使用基金会的知识价值和更广泛的影响审查标准的支持。

Anthrax is a globally distributed disease of wildlife, livestock, and humans. Successful prediction of and response to outbreaks of anthrax is limited by a lack of understanding of the geographic differences in the ecology of the pathogen as well as the pattern of disease outbreaks. This project will investigate the roles of host, pathogen, and environment to understand how the pathogen - host interaction evolves and contributes to the differences in anthrax occurrence between two study areas. The two areas, both in southern Africa, have very different anthrax outbreak dynamics, which are representative of variation in anthrax systems world-wide. In Etosha National Park, Namibia, there are smaller outbreaks, affecting grazing zebra, annually in wet seasons. In contrast, in Kruger National Park, South Africa, larger outbreaks affecting browsing kudu occur in dry seasons on roughly a decadal scale. The project builds on detailed records of disease and population dynamics in each park as well as archived pathogen samples and will involve new data collection and analyses and mathematical modeling to understand these different dynamics. Education, training, and scientific and public outreach are essential components of this research. Postdoctoral researchers and undergraduate and graduate students from diverse backgrounds will be trained in field, laboratory, and quantitative techniques emphasizing cutting-edge genomics, and statistical and dynamic modeling approaches. The causative agent of anthrax (the bacterium Bacillus anthracis), is often invoked as a textbook example for the evolution of high virulence and prolonged environmental survival. This project will link within-host, between-host, and in-environment processes, to understand how conflicting selective pressures impact pathogen diversity, host resistance, disease incidence, and ultimately, how these processes may drive host-pathogen co-evolution. This collaborative research team will compare anthrax dynamics in two wildlife systems, integrating long-term field studies, host and pathogen genomics, microbiology, and statistical and dynamic modeling. The project addresses three related questions: (1) how does pathogen diversity affect trade-offs between pathogen transmission and virulence? (2) how does host diversity affect trade-offs between pathogen transmission and virulence? and (3) how do landscape-scale patterns of transmission and host movement affect virulence-transmission trade-offs and host-pathogen population dynamics? Researchers will link variability in B. anthracis genomes to phenotype (i.e., pathogen survival in the environment, virulence to hosts, and transmission across host and geographic range). Researchers will identify host genes under pathogen-mediated selection in two primary host species, plains zebra (Equus quagga) and greater kudu (Tragelaphus strepsiceros). Researchers will build landscape-level models of epidemiology and population dynamics incorporating host movement, transmission routes, pathogen virulence, and host resistance. Finally, researchers will build models predicting anthrax transmission dynamics across ecosystems. In a broader sense, this research will facilitate the development of predictive tools to better manage public health and related policies for complex, multi-host zoonotic diseases such as anthrax.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.