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Serological Biomarkers for Coccidioidomycosis

球孢子菌病的血清学生物标志物

基本信息

批准号：
10296008
负责人：
DOUGLAS F. LAKE
金额：
$ 38.12万
依托单位：
ARIZONA STATE UNIVERSITY-TEMPE CAMPUS
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-06-07 至 2025-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10296008
关键词：
Activities of Daily Living Acute Acute Disease Aerosols American Antibiotics Antibodies Antibody Response Antibody titer measurement Antigens Area Arizona Bacterial Pneumonia Biological Assay Biological Markers Blastomycosis Blood Tests Bronchoalveolar Lavage California Categories Centers for Disease Control and Prevention (U.S.)Chronic Cloning Coccidioides Coccidioidomycosis Complement Coughing Data Development Diagnosis Diagnostic Diagnostic tests Disease Elderly Ensure Enzyme Immunoassay Enzyme-Linked Immunosorbent Assay Evaluation Fungal Spores Gold Growth Health Personnel Histoplasmosis Illness Days Immunoassay Immunocompetent Immunodiffusion Immunoglobulin G Immunoglobulin M Incidence Individual Infection Inhalation Laboratories Laboratory Diagnosis Learning Life Lung Measures Medical Meninges Morbidity - disease rate Nucleic Acids Patient Monitoring Patients Performance Phase Plasmids Pneumonia Population Precipitins Preparation Printing Procedures Production Prognosis Protein Array Protein Microchips Proteins Proteome Publishing Recombinants Reporting Reproducibility Reproduction spores Resources Sampling Schools Sensitivity and Specificity Serodiagnoses Serology Serology test Serum Sick Leave Site Skin Soil Specificity Sputum Standardization Surveys Symptoms System Testing Time Translating Tube Tuberculosis Validation Viral Viral Pneumonia Work accurate diagnosis antibody detection antigen detection bone clinical Diagnosis community acquired pneumonia cross reactivity desert fever diagnosis standard economic impact experience follow-up fungus immunoreactivity improved mortality performance tests prevent programs response retiree sample fixation screening seropositive success

项目摘要

PROJECT SUMMARY As of 2017, coccidioidomycosis (Cocci) also known as Valley Fever (VF) was designated a reportable disease in 22 states (1). The majority of the cases in the US occur in southern Arizona and California where the population is increasing with influx of naïve individuals, in particular, elderly retirees. Since Coccidioides sp, can cause significant morbidity and mortality in fully immunocompetent hosts, this represents an important threat to these regions where >10% percent of the US population resides, not including substantial tourist or part-time resident populations in Arizona and California. Importantly, the reporting criteria require a positive laboratory test for inclusion, yet ~50% of patients–who will eventually test positive–test negative while acutely ill (2). Testing has low sensitivity and specificity leaving sick patients and their health care providers without an accurate diagnosis. Thus, there is a profound need for better diagnostic approaches to properly identify Cocci patients to ensure appropriate follow-up and therapy ensues. Coccidioides spp. grow as mycelia in the desert soils and produce spores (arthroconidia) to survive during times of adverse growth conditions. When this soil is disturbed, arthroconidia aerosolize and are inhaled to initiate infection. Inside the host, the spores transform into spherules containing endospores which grow in the lung. When spherules burst, endospores, are released and can each disseminate to form a new spherule. Clinical diagnosis is difficult because patients’ symptoms resemble other bacterial and viral pneumonias. Laboratory diagnosis often relies solely on serology, but ~50% of patients do not test positive while they are acutely ill which results in inaccurate diagnosis an inappropriate treatment. We propose that it is time for a re- evaluation of seroreactive coccidioidal antigens. For the past six decades, serologic diagnosis of coccidioidomycosis has relied on IgM responses to tube precipitin (TP) and IgG responses to complement fixation (CF) antigens. Since these antigens are primarily expressed in mycelia, not in spherules which is the fungal form that grows in the host, it is not surprising that many patients are seronegative because they have not yet generated antibodies to spherule antigens during acute pulmonary illness. The GOAL of this proposal is to identify new coccidioidal antigens that react with acutely infected patient sera. The objectives are to utilize the recently published Coccidioides spp. proteome to create a nucleic acid programmable protein array (NAPPA) in which every coccidioidal protein is screened for reactivity with VF patient sera. Our hypothesis is that this survey of the Coccidioides proteome will reveal new spherule-phase antigens that are reactive with more patients, especially acutely ill patients who are seronegative for TP and/or CF antigens. Once we identify a small panel of seroreactive antigens, they can be incorporated into existing antigen preparations or a separate reliable, consistent, accurate test that will increase the number of positive diagnoses in acutely ill patients with early disease.

项目总结