Integrating Epidemiologic and Environmental Approaches to Understand and Predict Coccidioides Exposure and Coccidioidomycosis Emergence

项目摘要 球孢子菌病是一种感染所造成的吸入孢子从土壤居住的真菌球孢子 immitis或C. posadasii，并可能导致慢性肺部感染，脑膜炎或死亡。西南部各州是 目前正在经历有史以来最高的球孢子菌病发病率。这种疾病已经 在整个西南地区造成了巨大的人力和经济负担，估计总共有22亿美元。 仅在加州就有2000-2011年球孢子菌病相关住院治疗的费用。中的关键差距 了解阻碍了公共卫生反应，包括灰尘，病原体和个人风险 因素相互作用，以确定疾病的发病率，以及环境因素如何影响分布 病原体和灰尘的混合物为了解决这些差距，该项目调查了粉尘暴露的影响， 环境变异性和社会人口变化对球孢子菌属的影响。扩散、扩散和 球孢子菌感染率在加州。本研究主要有三个目的：1）调查 气候变化和粉尘暴露对球菌发病率时空分布的影响 从2000年到2018年的65，000个地理定位监测记录和病例交叉设计; 2）识别 C.环境来源在扰动和未扰动土壤中的高空间和时间分辨率下， 并确定风、降雨、土壤扰动和其他因素如何影响孢子传播， C.纵向取样在空气和土壤中的传染病;和3）预测病原体密度在空间上的变化， 时间和估计病原体密度和感染风险之间的因果关系， 病例交叉方法，对事件病例进行前瞻性监测。为了实现这些目标，研究 将联合收割机结合地理参考的球孢子菌病病例数据自2000年以来在加州在一个前所未有的 空间分辨率与细尺度粉尘浓度估计和环境数据的组合， 遥感、建模和地面监测。我们将使用新的现场和实验室方法进行 C.纵向取样immitis在空气和土壤中，确定如何微环境条件和循环 降雨和干旱模式决定病原体源动态，并确定支持 病原体通过空气传播。通过这些活动，我们将确定具体的粉尘条件， 造成感染的最大风险，估计病原体暴露和剂量反应关系，以及 评估风险群体和区域之间这种关系的异质性。研究结果将阐明 当前的流行，提高对球孢子菌属的分布和扩散的认识。在 环境，并确定高风险地区和亚群。获得的知识将支持决策- 在制定、设计和实施针对弱势群体的保护措施方面，

Project Summary Coccidioidomycosis is an infection caused by inhalation of spores from the soil-dwelling fungi Coccidioides immitis or C. posadasii, and can lead to chronic lung infection, meningitis, or death. Southwestern states are currently experiencing among the highest incidence rates of coccidioidomycosis ever recorded. The disease has levied a substantial human and economic burden throughout the southwest, totaling an estimated $2.2 billion in charges in California alone for coccidioidomycosis-associated hospitalizations from 2000-2011. Critical gaps in understanding have hindered the public health response, including how dust, pathogen, and individual risk factors interact to determine disease incidence, as well as how environmental factors influence the distribution of the pathogen and dust. To address these gaps, this project investigates the impacts of dust exposure, environmental variability, and sociodemographic change on Coccidioides spp. proliferation, dispersion, and coccidioidomycosis infection rates in California. The research focuses on three main aims: 1) investigate the influence of climate variation and dust exposure on the spatiotemporal distribution of cocci incidence using >65,000 geolocated surveillance records from 2000 to 2018 and a case-crossover design; 2) identify environmental sources of C. immitis at high spatial and temporal resolution in disturbed and undisturbed soil, and determine how wind, rainfall, soil disturbance and other factors influence spore dispersion through longitudinal sampling of C. immitis in air and soil; and 3) predict changes in pathogen density over space and time and estimate the exposure-response relationship between pathogen density and risk of infection using a case-crossover approach with prospective surveillance for incident cases. In pursuit of these aims, the research will combine georeferenced coccidioidomycosis case data across California since 2000 at an unprecedented spatial resolution with fine-scale dust concentration estimates and environmental data from a combination of remote sensing, modeling and ground monitors. We will use novel field and laboratory methods to conduct longitudinal sampling of C. immitis in air and soil, determining how microenvironmental conditions and cyclical patterns of rainfall and drought determine pathogen source dynamics, and identifying conditions that support pathogen dispersion through the air. Through these activities, we will identify the specific dust conditions that pose the greatest risk for infection, estimate pathogen exposure and the dose-response relationship, and evaluate heterogeneity in this relationship across risk groups and regions. The results will elucidate drivers of the current epidemic, enhance understanding of the distribution and dispersion of Coccidioides spp. in the environment, and identify high risk regions and subpopulations. The knowledge gained will support decision- makers in targeting, designing and implementing protective measures for vulnerable populations.