Immunodiagnostic Tests for the Rapid Diagnosis of Tb

快速诊断结核病的免疫诊断测试

• 批准号: 7460834
• 负责人: Jacqueline Michele Achkar
• 金额: $ 13.31万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-15 至 2012-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7460834
• 关键词: Abbreviations; Acid Fast Bacillae Staining Method; Acquired Immunodeficiency Syndrome; Adult; Advanced Development; Anti-Retroviral Agents; Antibodies; Antibody Formation; Antigens; Bacillus (bacterium); Biological Assay; Biometry; Calmette-Guerin Bacillus; Cause of Death; Centers for Disease Control and Prevention (U.S.); Class; Clinical; Clinical Research; Decision Making; Depth; Detection; Development Plans; Diagnosis; Directly Observed Therapy; Disease; Doctor of Medicine; Early identification; Enrollment; Enzyme-Linked Immunosorbent Assay; Epidemiology; Evaluation; Experimental Designs; Genus Mycobacterium; Goals; Gold; HIV; Health; Highly Active Antiretroviral Therapy; Hospitals; Hypersensitivity skin testing; Immunoassay; Immunoglobulin G; Immunoglobulins; Immunological Diagnosis; India; Infection; Interferons; Lung; Lung diseases; Malate Synthase; Medicine; Microscopic; Microscopy; Molecular Immunology; Monoclonal Antibodies; Mycobacterium tuberculosis; Negative Skin Test; New York; New York City; Nucleic Acids; Optics; Patient Isolation; Patients; Performance; Predictive Value; Prospective Studies; Proteins; Public Health; Pulmonary Tuberculosis; Recombinant Proteins; Recombinants; Relative (related person); Research Methodology; Research Personnel; Sampling; Sensitivity and Specificity; Serological; Serum; Site; Specificity; Sputum; Staging; Standards of Weights and Measures; T-Lymphocyte; Techniques; Testing; Thoracic Radiography; Time; Today; Training; Translational Research; Tuberculin; Tuberculosis; United States Food and Drug Administration; Universities; Viral Load result; Week; Whole Blood; base; career; clinical Diagnosis; college; density; improved; medical schools; mycobacterial; professor; programs; rapid diagnosis; research clinical testing; respiratory; response; tuberculin purified protein derivative; volunteer

DESCRIPTION (provided by applicant): This is a revised application from Jacqueline Achkar, M.D., who is an Assistant Professor in Medicine at the Albert Einstein College of Medicine. Her long-term goal is to become an independent investigator in clinical translational research related to tuberculosis (TB), HIV, and their occurrence as co-infections. The proposed career development plan will provide her with in-depth training in clinical research methods, immunology, molecular techniques, epidemiology, decision-making analysis and biostatistics. TB is a global leading public health problem and the leading cause of death in people with AIDS. There is an urgent need for early and accurate diagnosis of pulmonary TB (PTB) to achieve the CDC goal of elimination of TB in the US, improve TB control worldwide, and identify and treat active TB before development of advanced disease. Currently, there are no rapid tests with high sensitivity and specificity available for the diagnosis of all classes of active TB. The candidate proposes to examine the accuracy and clinical value of antibody detection to two immunodominant proteins of M. tb for the rapid diagnosis of PTB. The central hypothesis of this proposal is that antibody responses to these two proteins contain sufficient information to provide an accurate serodiagnostic test for PTB relative to an accepted gold standard. This test can serve as an useful adjunct to enhance the sensitivity of conventional rapid tests for PBT. The specific aims of this project are: (1) To assess the sensitivity, specificity and clinical value of the protein-based ELISA; (2) To determine total immunoglobulin (Ig) concentrations and titers of Ig isotypes and IgG subclasses to the two proteins, and compare them between HIV-infected and HIV-uninfected PTB patients; and (3) To test whether newly identified antigens of M. tb will enhance the sensitivity of the protein-based ELISA without compromising its specificity. This will be a prospective study. Consecutive adult patients (n=500) undergoing clinical evaluation for PTB will be enrolled from several hospital sites in New York City over a period of two years; 125/500 (25%) are expected to have TB by gold standard, and 40% of the enrolled patients are expected to be HIV-infected. The results of serum antibody reactivity to the immunodominant proteins of M. tb will be compared to the gold standard of culture, histological or clinically proven PTB. Specificity will be assessed in 200 randomly selected culture-negative subjects who are diagnosed with a pulmonary disease other than PTB.

描述（由申请人提供）：这是Jacqueline Achkar，M.D.的修订申请，他是阿尔伯特·爱因斯坦医学院的医学助理教授。她的长期目标是成为结核病（TB），艾滋病毒及其合并感染相关临床转化研究的独立研究者。拟议的职业发展计划将为她提供临床研究方法、免疫学、分子技术、流行病学、决策分析和生物统计学方面的深入培训。结核病是全球主要的公共卫生问题，也是艾滋病患者的主要死因。迫切需要对肺结核（PTB）进行早期和准确的诊断，以实现CDC在美国消除结核病的目标，改善全球结核病控制，并在晚期疾病发展之前识别和治疗活动性结核病。目前，没有高灵敏度和特异性的快速检测方法可用于诊断所有类型的活动性结核病。候选人建议检查抗体检测的准确性和临床价值的两个免疫显性蛋白的M。结核杆菌的快速诊断。该建议的中心假设是，对这两种蛋白质的抗体应答包含足够的信息，以提供相对于可接受的金标准的PTB的准确血清学诊断测试。此测试可以作为一个有用的辅助，以提高传统的快速测试PBT的灵敏度。本项目的具体目的是：（1）评价蛋白酶联免疫吸附试验（ELISA）的敏感性、特异性和临床应用价值;（2）测定两种蛋白的总免疫球蛋白（IG）浓度、IG亚型和IgG亚类的滴度，并比较HIV感染和未感染PTB患者的滴度;（3）检测新鉴定的结核分枝杆菌抗原是否为结核分枝杆菌抗原。结核杆菌将增强基于蛋白质的ELISA的灵敏度而不损害其特异性。这将是一项前瞻性研究。在为期两年的时间内，将从纽约市的几家医院入组接受PTB临床评价的连续性成人患者（n=500）;根据金标准，预计125/500（25%）患有TB，预计40%的入组患者为HIV感染者。血清抗体对M.结核病将与培养、组织学或临床证实的PTB的金标准进行比较。将在200例随机选择的培养阴性受试者中评估特异性，这些受试者被诊断患有除PTB以外的肺部疾病。