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

项目摘要 球孢子菌病是一种因吸入土壤真菌球孢子菌的孢子而引起的感染。 肺炎或波斯达氏弧菌，并可导致慢性肺部感染、脑膜炎或死亡。西南部各州 目前球孢子菌病的发病率是有记录以来最高的之一。这种疾病已经 在整个西南地区征收了大量的人力和经济负担，估计总额为22亿美元 2000-2011年，仅在加利福尼亚州就收取与球孢子菌病相关的住院费用。存在严重差距 理解阻碍了公共卫生反应，包括粉尘、病原体和个人风险 决定疾病发病率的因素相互作用，以及环境因素如何影响疾病的分布 病原体和灰尘。为了解决这些差距，该项目调查了粉尘暴露的影响， 环境变异性和球藻的社会人口学变化。扩散、扩散和 加州球孢子菌病感染率。这项研究主要集中在三个方面：1)调查 气候变化和粉尘暴露对沙眼衣原体感染时空分布的影响 &gt；从2000年到2018年的65,000个地理位置监控记录和病例交叉设计；2)确定 扰动和未扰动土壤中寄生线虫高时空分辨率的环境来源， 并确定风、降雨、土壤扰动和其他因素如何通过 空气和土壤中寄生虫的纵向采样；以及3)预测病原体密度在空间和空间上的变化 时间和估计在病原体密度和感染风险之间的暴露-反应关系 采用病例交叉方法，对事件病例进行前瞻性监测。为了追求这些目标，这项研究 将以史无前例的方式合并2000年以来加州各地的地理参考球孢子菌病病例数据 细尺度粉尘浓度估计和环境数据的空间分辨率 遥感、建模和地面监测。我们将使用新的现场和实验室方法来进行 空气和土壤中寄生线虫的纵向采样，确定微环境条件和循环 降雨和干旱的模式决定了病原体的来源动态，并确定了支持 病原体在空气中传播。通过这些活动，我们将确定特定的粉尘条件， 构成最大的感染风险，估计病原体暴露和剂量-反应关系；以及 评估这种关系在风险组和地区之间的异质性。这一结果将阐明 目前的疫情，提高了对球孢子虫分布和扩散的认识。在 环境，并确定高危区域和亚人群。所获得的知识将支持决策-- 在针对、设计和实施针对弱势群体的保护措施方面，制定者发挥了重要作用。

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.