Development of Coccidioides Cytokine Release Assay

球孢子菌病（CM）是一种由粗球孢子菌引起的地方性真菌病， 球孢子菌属Posadasii，原产于北美和南美的干旱地区。是 据估计，美国每年有多达35万人感染艾滋病毒。 这些地区的社区获得性肺炎病例被认为是CM的结果。 与CM相关的死亡率很高，中位病程为120天。的 与CM相关的成本很高，估计每年的直接医疗保健成本接近 两亿美元 目前，CM的诊断主要基于抗球孢子菌抗体的检测。 一旦感染清除，抗体最终变得不可检测，使其难以检测。 确定之前是否接触过典型的迟发型超敏反应 使用皮肤试验已被用于评估细胞免疫应答，这表明 过去的感染。市售球孢子菌皮试的性能不佳 这是一个很大的问题，在临床护理中不经常使用。 使用离体细胞因子释放测定（CRA）避免了与皮肤相关的局限性， 测试，同时允许检测由病原体刺激产生的细胞因子， 特异性抗原类似于市售的用于结核病的CRA， CRA将是患者护理和评估CM患病率的一个重大进步， 地理区域和人口。我们的数据表明，CM的CRA将作为一个有价值的 检测急性CM患者并对潜伏性CM患者进行分层的工具（处于 如果免疫抑制则重新激活）。气候变化和发病率模型预测地方性 从12个州扩大到18个州，发病率增加50%，强调需要 公共卫生筛查工具，为高风险建立不断变化的边界和分层 职业和未来的疫苗试验。 该应用程序的目标是开发一种测试，以帮助诊断，管理和 CM的流行病学，越来越多的人生活在或旅行通过的地区， 它是地方病。第一阶段赠款将利用技术进步和预测建模， 产生具有刺激细胞免疫的最高可能性的重组抗原 反应这些抗原将被用于开发一种管内CRA，这是第一种 帮助管理真菌疾病。

Coccidioidomycosis (CM) is an endemic mycosis caused by the fungi Coccidioides immitis and Coccidioides posadasii, which is native to arid regions of North and South America. It is estimated that up to 350,000 infections occur annually in the U.S. Additionally, up to a third of community acquired pneumonia cases in these areas are thought to be a result of CM. Morbidity associated with CM is substantial with a median illness duration of 120 days. The costs associated with CM are high, with an estimated annual direct healthcare cost of nearly $200 million. Currently, the diagnosis of CM is primarily based on detection of anti-Coccidioides antibodies. Once infection clears, the antibody eventually becomes undetectable making it difficult to determine if there was previous exposure. Classically, delayed-type hypersensitivity reactions using skin tests have been used to evaluate the cellular immune response, which is indicative of past infection. The commercially available Coccidioides skin test has suboptimal performance characteristics and is not utilized often in clinical care. The use of an ex vivo cytokine release assay (CRA) avoids the limitations associated with skin testing while allowing for the detection of cytokines produced by stimulation with a pathogen- specific antigen. Analogous to the commercially available CRA for tuberculosis, a Coccidioides CRA would be a major advance for patient care and for evaluation of CM prevalence within geographical regions and populations. Our data suggests a CRA for CM will be valuable as a tool to detect patients with acute CM and stratify those with latent CM (those at risk for reactivation if immunosuppressed). Climate change and incidence modelling predict endemicity to expand from 12 to 18 states and incidence to increase by 50%, stressing the need for a public health screening tool to establish changing boundaries and stratification for high risk occupations and future vaccine trials., The goal of this application is to develop a test to assist in the diagnosis, management, and epidemiology of CM, which increasingly afflicts people living in or travelling through areas where it is endemic. This phase 1 grant will utilize technological advances and prediction modeling to produce recombinant antigens with the highest likelihood of stimulating a cellular immune response. These antigens will then be used to develop an in-tube CRA, the first of its kind to assist in the management of a fungal disease.