Immunodiagnostic Tests for the Rapid Diagnosis of Tb

快速诊断结核病的免疫诊断测试

基本信息

批准号：
8071604
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
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-07-15 至 2012-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8071604
关键词：
Acid Fast Bacillae Staining Method Acquired Immunodeficiency Syndrome Adult Antibodies Antibody Formation Antigens Bacillus (bacterium)Biological Assay Biometry Cause of Death Centers for Disease Control and Prevention (U.S.)Clinical Clinical Research Decision Making Detection Development Development Plans Diagnosis Doctor of Medicine Early identification Enrollment Enzyme-Linked Immunosorbent Assay Epidemiology Evaluation Experimental Designs Goals Gold HIV Hospitals Immunoassay Immunoglobulin G Immunoglobulin Isotypes Immunoglobulins Immunological Diagnosis India Infection Lung diseases Malate Synthase Medicine Microscopic Microscopy Molecular Immunology Mycobacterium tuberculosis New York City Nucleic Acids Patient Isolation Patients Performance Prospective Studies Proteins Public Health Pulmonary Tuberculosis Recombinant Proteins Relative (related person)Research Methodology Research Personnel Sampling Sensitivity and Specificity Serological Serum Site Specificity Sputum Staging T-Lymphocyte Techniques Testing Time Training Translational Research Tuberculin Test Tuberculosis advanced disease base career development college improved mycobacterial professor programs rapid diagnosis research clinical testing respiratory response volunteer

项目摘要

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）：这是医学博士Jacqueline Achkar的修订申请，他是Albert Einstein医学院医学助理教授。她的长期目标是成为与结核病（TB），艾滋病毒（TB），HIV及其作为共同感染的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的深入培训。结核病是全球领先的公共卫生问题，也是艾滋病患者的主要死亡原因。迫切需要对肺结核（PTB）的早期和准确诊断，以实现美国消除结核病的目标，在全球范围内改善结核病控制，并在发展晚期疾病之前识别和治疗活跃的结核病。当前，尚无高灵敏度和特异性的快速测试，可用于诊断所有类别的活性结核病。候选人建议检查M. TB的两种免疫主导蛋白的抗体检测的准确性和临床值，以快速诊断PTB。该提案的中心假设是，对这两种蛋白质的抗体反应包含足够的信息，可为PTB提供准确的血清诊断测试，相对于公认的黄金标准。该测试可以作为提高常规快速测试对PBT的灵敏度的有用辅助。该项目的具体目的是：（1）评估基于蛋白质ELISA的灵敏度，特异性和临床价值；（2）确定Ig同种型和IgG亚类的总免疫球蛋白（Ig）浓度以及两种蛋白质的滴度，并将其在HIV感染和HIV未感染的PTB患者之间进行比较；（3）测试新鉴定的M. TB抗原是否会增强基于蛋白质的ELISA的敏感性，而不会损害其特异性。这将是一项前瞻性研究。经过PTB临床评估的连续成人患者将在纽约市的几个医院中招募PTB的临床评估。预计125/500（25％）将按黄金标准使用结核病，预计有40％的入学患者将受到HIV感染。将M. TB免疫主导蛋白的血清抗体反应性与组织学或临床证明的PTB的黄金标准进行比较。将在200名被诊断出患有PTB以外的肺部疾病的随机选择的培养基（随机选择）中评估特异性。