Development of Coccidioides Cytokine Release Assay

球孢子菌细胞因子释放测定的发展

基本信息

批准号：
10760131
负责人：
Eric Holbrook
金额：
$ 99.92万
依托单位：
MIRAVISTA DIAGNOSTICS, LLC
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-08-01 至 2026-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10760131
关键词：
Academic Medical Centers Acute Antibodies Antifungal Therapy Antigens Area Arizona Biological Assay Blood specimen Cell Survival Cellular Immunity Characteristics Clinical Coccidioides Coccidioides immitis Coccidioides posadasii Coccidioidomycosis Data Dedications Delayed Hypersensitivity Detection Development Diagnosis Diagnostic Diagnostic tests Disease Epidemiology Evaluation Future Geographic Locations Goals Grant Health Care Costs Hour Hypersensitivity skin testing Immune response Immunity Immunocompromised Host Immunosuppression Incidence Individual Infection Interferons Laboratories Life Marketing Measures Methods Monitor Morbidity - disease rate North America Occupations Organ Transplantation Outcome Patient Care Patients Performance Persons Phase Physicians Population Predictive Value Prevalence Preventive Public Health ROC Curve Reaction Recombinants Risk Screening procedure Serodiagnoses Serology test Serum Shipping Solid Source South America Specificity Standardization Stratification Stress T-Lymphocyte Temperature Testing Therapeutic immunosuppression Travel Tuberculosis United States Universities Vaccines Whole Blood acute infection care costs climate change clinical care community acquired pneumonia cost cytokine desert fever detection assay fungus geographic population high risk immunological status immunosuppressed latent infection mortality novel novel diagnostics pathogen post-market predictive modeling prognostic prognostic value prototype recruit response risk mitigation risk stratification screening stem cells tool vaccine trial

Academic Medical Centers Acute Antibodies Antifungal Therapy Antigens Area Arizona Biological Assay Blood specimen Cell Survival Cellular Immunity Characteristics Clinical Coccidioides Coccidioides immitis Coccidioides posadasii Coccidioidomycosis Data Dedications Delayed Hypersensitivity Detection Development Diagnosis Diagnostic Diagnostic tests Disease Epidemiology Evaluation Future Geographic Locations Goals Grant Health Care Costs Hour Hypersensitivity skin testing Immune response Immunity Immunocompromised Host Immunosuppression Incidence Individual Infection Interferons Laboratories Life Marketing Measures Methods Monitor Morbidity - disease rate North America Occupations Organ Transplantation Outcome Patient Care Patients Performance Persons Phase Physicians Population Predictive Value Prevalence Preventive Public Health ROC Curve Reaction Recombinants Risk Screening procedure Serodiagnoses Serology test Serum Shipping Solid Source South America Specificity Standardization Stratification Stress T-Lymphocyte Temperature Testing Therapeutic immunosuppression Travel Tuberculosis United States Universities Vaccines Whole Blood acute infection care costs climate change clinical care community acquired pneumonia cost cytokine desert fever detection assay fungus geographic population high risk immunological status immunosuppressed latent infection mortality novel novel diagnostics pathogen post-market predictive modeling prognostic prognostic value prototype recruit response risk mitigation risk stratification screening stem cells tool vaccine trial

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项目摘要

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 CRA 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 II grant will seek to establish and define the prototype assay for clinical use.

球霉菌病（CM）是由真菌球虫炎和球虫下posadasii，原产于北美和南美的干旱地区。这是估计每年在美国发生多达350,000次感染，最高三分之一社区在这些地区获得的肺炎病例被认为是CM的结果。与CM相关的发病率很大，中位疾病持续时间为120天。这与CM相关的成本很高，估计的年度直接医疗保健成本几乎为 2亿美元。当前，CM的诊断主要基于检测抗coccidioides抗体的检测。一旦感染清除，抗体最终就变得无法检测到确定是否有以前的曝光。经典，延迟型超敏反应使用皮肤测试已用于评估细胞免疫反应，这表明过去的感染。市售的球菌素皮肤测试的性能均高于最佳性能特征，不经常用于临床护理。使用离体细胞因子释放测定法（CRA）避免了与皮肤相关的局限性测试同时允许检测通过病原体刺激产生的细胞因子特异性抗原。类似于肺结核的市售CRA，Coccidioides CRA将是患者护理和评估CM患病率的重大进步地理区域和人口。我们的数据表明，CM的CRA将很有价值检测急性CM患者并分层患有潜伏CM的工具（有风险的患者如果免疫抑制）。气候变化和发病率建模预测流行性从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以建立不断变化的界限和分层以实现高风险职业和未来的疫苗试验，该应用的目的是开发CRA来协助诊断，管理和 CM的流行病学，越来越多地困扰着生活在或旅行的人这是地方性的。该第二阶段赠款将寻求建立和定义临床原型测定法使用。