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）：这是由医学博士 Jacqueline Achkar 修改后的申请，她是阿尔伯特·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，也是艾滋病患者死亡的主要原因。迫切需要对肺结核（PTB）进行早期、准确的诊断，以实现美国疾病预防控制中心消除结核病的目标，改善全球结核病控制，并在发展为晚期疾病之前识别和治疗活动性结核病。目前，还没有具有高敏感性和特异性的快速检测方法可用于诊断所有类别的活动性结核病。候选人提议检查结核分枝杆菌两种免疫显性蛋白的抗体检测对于PTB快速诊断的准确性和临床价值。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，可以相对于公认的金标准为 PTB 提供准确的血清诊断测试。该测试可以作为有用的辅助手段，提高 PBT 常规快速测试的灵敏度。本项目的具体目的是：（1）评估基于蛋白质的ELISA的敏感性、特异性和临床价值； (2) 测定两种蛋白的总免疫球蛋白（Ig）浓度以及Ig同种型和IgG亚类的滴度，并在HIV感染者和未感染HIV的PTB患者之间进行比较； (3) 测试新鉴定的结核分枝杆菌抗原是否会增强基于蛋白质的 ELISA 的敏感性而不损害其特异性。这将是一项前瞻性研究。将在两年内从纽约市的多个医院地点连续招募接受 PTB 临床评估的成年患者 (n=500)；按照金标准，预计 125/500 (25%) 的患者患有结核病，并且 40% 的入组患者预计感染 HIV。结核分枝杆菌免疫显性蛋白的血清抗体反应结果将与培养、组织学或临床证明的结核病金标准进行比较。特异性将在 200 名随机选择的培养阴性受试者中进行评估，这些受试者被诊断患有 PTB 以外的肺部疾病。