Evaluation of a point-of-care immunochromatographic assay for enteric fever

肠热病即时免疫层析检测的评估

基本信息

批准号：
10392476
负责人：
Jason Randolph Andrews
金额：
$ 14.18万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
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：
2021-04-13 至 2024-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10392476
关键词：
Acute Africa Africa South of the Sahara Age Antibiotics Antibodies Antigens Antimicrobial Resistance Area Asia Bacteremia Bacterial Infections Bangladesh Biological Assay Blood Blood capillaries Blood specimen Cessation of life Characteristics Clinical Clinical Management Collaborations Conjugate Vaccines Country Data Dengue Diagnosis Diagnostic Diagnostic tests Disease Enrollment Enteral Enzyme-Linked Immunosorbent Assay Etiology Evaluation Fever Fingers Funding Goals Health system Hemolysin Immunoglobulin A Individual Infection Lateral Lipopolysaccharides Modeling Morbidity - disease rate Nepal Paratyphoid Fever A Participant Patients Performance Plasma Population Heterogeneity Predictive Value Rapid diagnostics Reader Reference Standards Resistance Resource-limited setting Resources Rickettsia Risk Salmonella Salmonella enterica Salmonella infections Salmonella paratyphi Salmonella typhi Sampling Scrub Typhus Sensitivity and Specificity Serodiagnoses Serotyping Serum Specificity Speed System Technology Testing Time Typhoid Fever Venipunctures Whole Blood Work acute infection antimicrobial base biobank burden of illness case control chikungunya clinical care clinical diagnosis cohort cost effective diagnostic assay diagnostic tool emerging antimicrobial resistance extensive drug resistance impression improved low and middle-income countries molecular diagnostics novel point of care point-of-care diagnostics portability programs prospective response surveillance study tool

项目摘要

PROJECT SUMMARY Enteric fever, an invasive bacterial infection caused by Salmonella enterica serotypes Typhi and Paratyphi A, B, and C, remains a major cause of illness and death globally. Timely diagnosis and treatment are critical to reducing morbidity and risk of serious complications from enteric fever. However, there are currently no diagnostics with sufficient accuracy and speed for guiding treatment decisions. Rapid serologic diagnostics have low predictive value, particularly in typhoid-endemic settings. Blood culture has high specificity, but sensitivity is estimated at 60%, and results take 2-4 days to become available. Through high-throughput immunoscreens, we found that IgA antibodies to hemolysin E (HlyE) and S. Typhi lipopolysaccharide (LPS) are robust markers of acute enteric fever, reliably distinguishing patients with enteric fever from those with other acute infections in Nepal and Bangladesh (AUC 0.95). We have further developed a point-of-care immunochromatographic assay, using Chembio's dual path platform (DPP®) technology, to quantify anti-HlyE and anti-LPS IgA responses. Our preliminary data demonstrated excellent concordance with ELISA and high accuracy in distinguishing enteric fever cases from controls. We now propose to: 1) evaluate the accuracy of the DPP Typhoid assay using biobanked plasma from patients with enteric fever and a diverse array of other febrile illnesses collected from multi-country surveillance studies in South Asia and sub-Saharan Africa; and 2) prospectively evaluate the DPP Typhoid assay with fingerstick capillary blood among individuals with acute febrile illness in a typhoid-endemic setting. These studies will leverage diverse, globally representative enteric fever surveillance platforms, investigate alternative etiologies of febrile illness, and rigorously test the novel assay performance in direct comparison with existing enteric fever diagnostics. Successful completion of this project would fill a major gap in diagnostics for enteric fever which could improve clinical management, reduce overdiagnosis and unnecessary antibiotic use, and facilitate enteric fever control initiatives.

项目概要肠热病是一种由肠沙门氏菌血清型伤寒和伤寒引起的侵袭性细菌感染甲型、乙型和丙型副伤寒仍然是全球疾病和死亡的主要原因。和治疗对于降低肠道严重并发症的发病率和风险至关重要然而，目前还没有足够准确和快速的诊断方法来指导。快速血清学诊断的预测价值较低，尤其是在治疗决策中。伤寒流行情况下，血培养具有很高的特异性，但敏感性估计为 60%，通过高通量免疫筛选，我们需要 2-4 天才能获得结果。发现溶血素 E (HlyE) 和伤寒沙门氏菌脂多糖 (LPS) 的 IgA 抗体急性肠热病的强有力标志物，可靠地区分肠热病患者尼泊尔和孟加拉国患有其他急性感染的患者（AUC 0.95）。使用 Chembio 的双路径平台开发了一种即时免疫色谱测定法 (DPP®) 技术，用于量化抗 HlyE 和抗 LPS IgA 反应我们的初步数据。与 ELISA 具有出色的一致性，并且在区分肠溶菌方面表现出较高的准确性我们现在建议： 1) 评估 DPP 伤寒的准确性。使用来自肠热病患者和各种其他疾病患者的生物库血浆进行检测从南亚和撒哈拉以南地区的多国监测研究中收集的发热性疾病非洲；2) 通过指尖毛细血管血测定前瞻性评估 DPP 伤寒测定这些研究将在伤寒流行环境中患有急性发热性疾病的个体中进行。利用多样化的、具有全球代表性的肠热病监测平台，开展调查发热性疾病的替代病因，并直接严格测试新的检测性能与现有的肠热诊断进行比较，该项目的成功完成将。填补了肠热病诊断方面的重大空白，可以改善临床管理，减少肠热病的发生。过度诊断和不必要的抗生素使用，并促进肠热控制举措。