Enhancing detection and mobile monitoring of schistosomiasis with urine-based analyte pre-concentration technology

利用基于尿液的分析物预浓缩技术加强血吸虫病的检测和移动监测

基本信息

批准号：
10697011
负责人：
Cody Carrell
金额：
$ 27.55万
依托单位：
SALUS DISCOVERY, LLC
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-04-01 至 2025-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10697011
关键词：
Academic Medical Centers Address Adult Antigens Area Biological Assay Blood Buffers Centrifugation Cessation of life Chronic Disease Clinical Clinical Research Clinical Sensitivity Clinical Trials Communicable Diseases Communities Consumption Data Detection Devices Diagnostic Diagnostic Sensitivity Diagnostic Specificity Diagnostic tests Disease Feces Friends Goals HIV HIV/AIDS Human Immunoassay Improve Access Individual Infection Infrastructure Interruption Laboratories Lateral Malaria Maps Measures Methods Microscopy Monitor Morbidity - disease rate Parasitic Diseases Patients Performance Persons Pharmaceutical Preparations Phase Pilot Projects Population Prevalence Process Reproducibility Research Resources Sampling Schistosoma Schistosoma mansoni Schistosomiasis Serum Site Small Business Innovation Research Grant Snails Specificity Techniques Technology Testing Time Training Treatment Efficacy Urine Water World Health Organization antigen detection burden of illness commercialization cross reactivity detection limit detection method disability-adjusted life years disorder control egg experience field study first-in-human global health health organization human study improved interest lateral flow assay new technology performance tests point of care prototype response success transmission process treatment response vector

项目摘要

ABSTRACT Schistosomiasis is a debilitating parasitic disease that infects over 230 million people and causes 280,000 deaths per year. New estimates of global disease burden rank schistosomiasis as the third most impactful infectious disease behind only HIV/AIDS and malaria. Therefore, over the past decade, global health organizations have renewed interest in schistosomiasis control and elimination. Efforts to reduce schistosomiasis-associated morbidities primarily involve mass drug administration (MDA) and measures for interrupting transmission (e.g., via improved access to safe water and snail (vector) control). Critical to both disease control strategies is the ability to detect infected individuals; however, because highly endemic areas often lack basic laboratory infrastructure, it is vital that monitoring be performed in the field or at the point-of-care (POC) to address the vast numbers of sites and individuals needing testing. Current disease monitoring largely depends upon microscopy techniques to identify/quantify eggs that are sporadically shed by adult worms in stool or urine. While highly specific, microscopy methods are laborious, time-consuming, inconsistent, and often have clinical sensitivities under 5%. Alternatives to microscopy include immunoassays that detect schistosome- specific antigens, such as the circulating cathodic antigen (CCA), or the circulating anodic antigen (CAA), from human urine. A POC CCA urine assay has been commercialized and used in surveillance and mapping studies, but is not sensitive enough to detect low-intensity infections, and is only reliably produced by one of the six common Schistosoma species, which limits its use to certain regions. In contrast, CAA is produced by all Schistosoma species and, unlike microscopy, is directly correlated to total worm burden for monitoring therapy response. Therefore, a CAA immunoassay is expected to significantly enhance diagnostic monitoring of schistosomiasis, but no commercially available POC-CAA assay exists. To address this unmet need, we will integrate two complementary technologies that enable ultra-sensitive POC field-testing for schistosomiasis from urine. Our collaborator, Dr. Paul Corstjens, a globally recognized schistosomiasis expert at Leiden University Medical Center, has developed an ultrasensitive Up-Converting Phosphor Lateral Flow Assay (UCP-LFA) for CAA detection. The assay has shown tremendous promise in several studies and clinical trials but still requires time- consuming and resource-intensive sample pre-concentration to reach the sensitivity required to detect the lowest-intensity infections. In parallel, Salus Discovery has developed a new technology, termed FLOW™, that expands upon the operational concepts of LFAs by enabling pre-concentration of analytes from 20 mL of urine into 100 µL prior to detection on an LFA. Recently, Salus and Dr. Corstjens' group developed the first prototype of a device that integrates FLOW urine pre-concentration with a UCP-LFA readout (FLOW-S). The FLOW-S prototype was preliminarily evaluated with a set of 30 clinical samples where it achieved 79% sensitivity and 100% specificity, demonstrating its use as a fundamentally new, POC-friendly, ultra-sensitive CAA-based assay for schistosomiasis. In this SBIR Phase 1 proposal we will build upon our success by optimizing the FLOW-S device to achieve a detection limit of 0.1 pg/mL, enabling detection of even the lowest intensity (i.e., single-worm) infections (Aim 1), and performing a clinical study with fresh urine samples (Aim 2).

抽象的血吸虫病是一种使人衰弱的寄生虫病，每年感染超过 2.3 亿人，并导致 28 万人死亡。对全球疾病负担的新估计将血吸虫病列为第三大影响最大的传染病，仅次于因此，在过去十年中，全球卫生组织对艾滋病毒/艾滋病和疟疾重新产生了兴趣。控制和消除血吸虫病减少血吸虫病相关发病率的努力主要涉及群众。药物管理 (MDA) 和阻断传播的措施（例如，通过改善获得安全水和蜗牛的机会）（媒介）控制）然而，这两种疾病控制策略的关键是检测受感染个体的能力；高流行地区往往缺乏基本的实验室基础设施，因此在现场或现场进行监测至关重要护理点 (POC) 来满足大量需要检测的场所和个人的需求。当前的疾病监测很大程度上依赖于显微镜技术来识别/量化零星脱落的虫卵粪便或尿液中的成虫虽然具有高度特异性，但显微镜方法费力、耗时且不一致，临床敏感性通常低于 5% 显微镜检查的替代方法包括检测血吸虫的免疫测定法。来自人类的特定抗原，例如循环阴极抗原（CCA）或循环阳极抗原（CAA） POC CCA 尿液已商业化并用于监测和绘图研究，但不是敏感的检测方法。足以检测低强度感染，并且仅由六种常见血吸虫物种之一可靠地产生，相比之下，CAA 是由所有血吸虫属物种产生的，并且与显微镜检查不同。与监测治疗反应的总蠕虫负荷直接相关，因此，CAA 免疫测定有望发挥作用。显着增强了血吸虫病的诊断监测，但尚无商业化的 POC-CAA 检测方法。为了解决这一未满足的需求，我们将集成两种互补技术，以实现超灵敏的 POC 现场测试我们的合作者 Paul Corstjens 博士是莱顿大学全球公认的血吸虫病专家。大学医学中心开发了一种超灵敏上转换荧光粉横向流动测定 (UCP-LFA) CAA 检测在多项研究和临床试验中显示出巨大的前景，但仍需要时间。消耗和资源密集型样品预浓缩，以达到检测最低强度所需的灵敏度与此同时，Salus Discovery 开发了一项名为 FLOW™ 的新技术，该技术扩展了 LFA 的操作概念，在检测前将 20 mL 尿液中的分析物预浓缩至 100 µL 最近，Salus 和 Corstjens 博士的团队开发了第一个集成 FLOW 尿液的设备原型。使用 UCP-LFA 读数器 (FLOW-S) 进行预浓缩 FLOW-S 原型通过一组进行了初步评估。在 30 个临床样本中，它实现了 79% 的敏感性和 100% 的特异性，证明了它作为一种全新的、 POC 友好型、超灵敏的基于 CAA 的血吸虫病检测方法在本 SBIR 第一阶段提案中，我们将基于我们的研究成果。通过优化 FLOW-S 设备，成功实现了 0.1 pg/mL 的检测限，甚至能够检测最低的强度（即单蠕虫）感染（目标 1），并使用新鲜尿液样本进行临床研究（目标 2）。