Cross-immunity and geographical invasion in sylvatic T. cruzi transmission

该项目开发了在美国和墨西哥北部相互作用的克氏锥虫传播周期的详细的、空间上明确的模型，这些模型在种群水平上很少被研究。克氏锥虫引起恰加斯病。寄生虫种类、寄主和病媒物种(主要是浣熊、负鼠和林鼠，以及昆虫病媒血吸虫和沙鼠)及其特征的差异使每个周期具有不同的动态，但媒介传播将它们耦合在一起。气候变化，无论是长期的还是季节性的，都通过调节媒介行为来影响这些动态，创造了非本地菌株地理入侵的可能性，而在美国观察到的菌株之间的交叉免疫，加上每个周期特有的寄生虫适应，在菌株之间建立了竞争，可能允许本地(地方性)菌株形成这种入侵的屏障。该项目开发了详细的小规模模型(基于试剂和分析)来研究局部效应(如扩散)如何影响全球动态，详细的大规模模型来研究结果全球动态，以经典的集合种群模型(具有常微分方程和随机微分方程的动力系统)为基线，不仅可以得到更详细的模型，还可以得到可用于预测和解释数值结果的定性、分析和概率结果。该项目的四个结构阶段在地方和区域尺度上开发了低空间分辨率和高空间分辨率的相应模型，而覆盖所有模型框架的是对气候对媒介饲养、成熟、流动性和随后感染率的影响的研究。该项目的数学重点是开发一种多层次的建模方法，其中局部和全球因素相互影响，而生物学的中心是需要了解克鲁兹线虫对不同传播途径(僵尸、垂直和口腔)的进化适应之间的复杂相互作用，以响应局部媒介行为，温度和湿度差异驱动的媒介行为变化，以及传播引起的传播周期之间的通信。这项研究不仅回答了与这些模型和生物系统相关的具体问题，而且在新出现/重新出现的病媒传播疾病、多尺度建模和生态系统对气候变化的响应方面提供了一个重要的案例研究。这项工作涉及与格鲁吉亚(美国)、法国和墨西哥的合作研究人员进行多学科和国际合作，这些研究人员拥有媒介种群生物学、进化适应、土地利用和公共卫生问题的专业知识，以及建模的各个方面，以及本科生和研究生和博士后研究员，他们将在项目工作期间获得跨学科协作研究和指导技能的培训。

This project develops detailed, spatially explicit models for the several sylvatic transmission cycles of Trypanosoma cruzi, which causes Chagas' disease, interacting in the U.S. and northern Mexico, which have been little studied at the population level. Differences in parasite strain, host and vector species (primarily raccoons, opossums, and woodrats, and the insect vectors Triatoma sanguisuga and gerstaeckeri), and their characteristics give each cycle distinct dynamics, but vector dispersal couples them together. Climate changes, both long-term and seasonal, affect these dynamics by regulating vector behavior, creating a potential for geographical invasion of non-native strains, while observed cross-immunity between strains in the U.S., together with parasite adaptations particular to each cycle, set up a competition between strains that may allow native (enzootic) strains to form a barrier to such invasion.The project develops detailed small-scale models (agent-based as well as analytical) to study how local effects (like dispersal) affect global dynamics, detailed large-scale models to study the result-ing global dynamics, with classical metapopulation models (dynamical systems with both ordinary and stochastic differential equations) as a baseline from which to derive not only the more detailed models but also qualitative analytical and probabilistic results which can be used to anticipate and interpret numerical results. Four structural phases of the project develop corresponding models at low and high spatial resolution on local and regional scales, while overlaid across all model frameworks is the study of climate effects on vector feeding, maturation, mobility, and subsequent infection rates. The mathematical focus of the project is the development of a multi-level modeling approach in which local and global factors influence each other, while the biology centers around the need to understand the complex interactions between the evolutionary adaptations to different transmission avenues (stercorarian, vertical and oral) made by T. cruzi in response to local vector behavior, changes in vector behavior driven by differences in temperature and humidity, and the communications between transmission cycles caused by dispersal. The research not only answers the specific questions posed relative to these models and biological systems, but also provides an important case study in the areas of emerging/re-emerging vector-borne diseases, multiscale modeling, and ecosystem responses to climatic change.This work involves a multidisciplinary and international collaboration with cooperating researchers in Georgia (U.S.), France and Mexico with expertise in vector population biology, evolutionary adaptations, land use and public health issues, and various aspects of modeling, as well as with undergraduate and graduate students and a postdoctorate researcher who will gain training in interdisciplinary collaborative research and mentoring skills while working on the project.