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

• 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
• 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

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.

项目摘要 肠道发热，一种由伤寒沙门氏菌引起的侵袭性细菌感染， 甲型、B和丙型副伤寒仍然是全球疾病和死亡的主要原因。及时诊断 和治疗对于降低肠道疾病的发病率和严重并发症的风险至关重要。 发烧然而，目前还没有足够准确和快速的诊断方法来指导 治疗决定。快速血清学诊断的预测价值较低，特别是在 伤寒流行的环境。血培养特异性高，但敏感性估计为60%， 并且结果需要2-4天才能获得。通过高通量免疫筛选，我们 发现溶血素E（HlyE）和S.伤寒脂多糖（LPS）是 强有力的急性肠热病标志物，可靠地区分肠热病患者和 尼泊尔和孟加拉国的其他急性感染者（AUC 0.95）。我们进一步 利用Chembio的双通道平台开发了一种即时免疫色谱分析方法 (DPP®）技术，以量化抗HlyE和抗LPS伊加应答。我们的初步数据 结果显示，与ELISA具有良好的一致性，并且在区分肠 对照组的发热病例。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的生物库血浆和各种其他 从南亚和撒哈拉以南非洲多国监测研究中收集的发热性疾病 非洲;和2）前瞻性评价手指针刺毛细血管血的DPP伤寒检测 在伤寒流行环境中急性发热性疾病的个体中。这些研究将 利用多样化的、具有全球代表性的肠热病监测平台， 发热性疾病的替代病因，并严格测试新的检测试剂盒性能， 与现有的伤寒诊断方法进行比较。该项目的成功完成将 填补了肠热病诊断方面的重大空白，这可以改善临床管理，减少 过度诊断和不必要的抗生素使用，并促进肠热病控制举措。