Multiple Antigen Point-of-Care Device for Improved Syphilis Diagnosis

描述（由申请人提供）：Precision Photonics Corporation的mBio Diagnostics部门（mBio/PPC）正在开发一种低成本、床旁（POC）、组合密螺旋体/非密螺旋体梅毒诊断器械。该检测将建立在mBio SnapEsiTM多重血清学系统上，该系统通过同时测量针对多种抗原的抗体来进行血清学疾病诊断。梅毒仍然是一个主要的公共卫生问题。它是一种由梅毒螺旋体引起的性传播和先天性疾病。当正确诊断时，它很容易用相对便宜的抗菌疗法治疗。在地球仪范围内，每年梅毒感染的统计数字是严峻的，有1200万人感染。先天性梅毒每年导致100多万婴儿死亡。梅毒感染在艾滋病毒感染的情况下特别严重，因为活动性梅毒的生殖器溃疡增加了艾滋病毒传播的风险。与此同时，梅毒疾病的进展大大加快免疫功能低下的个人。大多数目前的梅毒检测是基于几十年的历史，实验室为基础的，非梅毒螺旋体测试（RPR和VDRL）与多测试算法中的验证性测试一起使用。密螺旋体快速检测已在全球市场推出，并提供即时结果的优势。然而，快速检测不能提供非密螺旋体检测所提供的活动性疾病定量滴度信息。改进的护理点梅毒检测将导致更好的个体患者结果，减少疾病传播，并可能降低整体医疗保健系统成本。在这里，我们建议开发简单，低成本，组合密螺旋体/非密螺旋体床旁梅毒诊断系统，称为SnapEsiTM Syphony T/NT。mBio/PPC目前在其SnapEsi POC诊断系统上进行了初步的密螺旋体血清学检测。SnapEsi是一种基于生物标志物面板的最小仪器化、基于微阵列的检测设备。拟议研究的第一阶段将侧重于开发定量非密螺旋体检测和选择最终的密螺旋体抗原。与加州大学圣地亚哥分校的传染病临床医生合作，将采集100份临床样本并进行表征，作为第一阶段的一部分，为初步的灵敏度和特异性计算提供基础。第一阶段将该技术定位于第二阶段更大的测试开发和流行病学工作。第二阶段将侧重于艾滋病毒合并感染背景下的临床检测、检测经济学和疾病流行病学。拟议的系统填补了改善POC梅毒检测的一个重要的未满足的需求，同时建立了一个平台，最终多病原体测试推出。长期愿景是梅毒快速检测，在同一个测试盒中进行平行的HIV检测。这种系统提供了在资源有限的情况下节省大量成本的机会，在这种情况下，多种人工、单一病原体的快速检测将变得昂贵和笨重。

DESCRIPTION (provided by applicant): The mBio Diagnostics division of Precision Photonics Corporation (mBio/PPC) is developing a low-cost, point-of-care (POC), combination Treponemal/Nontreponemal Syphilis diagnostic device. The Syphilis test will be built on the mBio SnapEsiTM multiplexed serology system, which performs serological disease diagnosis by simultaneously measuring antibodies against multiple antigens. Syphilis remains a major public health concern. It is a sexually transmitted and congenital disease caused by the bacterium Treponema pallidum. When properly diagnosed, it is readily treatable with relatively inexpensive antimicrobial therapies. Around the globe, annual syphilis infection statistics are grim, with 12 million people infected. Congenital syphilis kills more than one million infants per year. Syphilis infection is particularly grave in the context of HIV infection, as genital ulcers in active syphilis increase the risk of HIV transmission. At the same time, syphilis disease progression is greatly accelerated in immunocompromised individuals. Most current syphilis testing is based on decades-old, laboratory-based, nontreponemal tests (RPR & VDRL) utilized with confirmatory testing in multi-test algorithms. Treponemal rapid tests have been introduced in global markets and offer the advantage of a point-of-care result. The rapid tests, however, do not deliver the active disease quantitative titer information provided by the nontreponemal tests. Improved point-of-care syphilis testing will lead to better individual patient outcomes, reduced disease spread, and will potentially reduce overall healthcare system costs. Here we propose development of simple, low-cost, combination Treponemal / Nontreponemal point-of-care syphilis diagnostic system called the SnapEsiTM Syphilis T/NT. mBio/PPC currently has a preliminary Treponemal serology assay working on its SnapEsi POC diagnostic system. SnapEsi is a minimally instrumented, cartridge-based device for assays based on panels of biomarkers. Phase I of the proposed research will focus on development of a quantitative nontreponemal assay and selection of the final set of Treponemal antigens. Working with infectious disease clinicians at the University of California, San Diego, 100 clinical samples will be sourced and characterized as part of Phase I, providing the basis for preliminary sensitivity and specificity calculations. Phase I positions the technology for a larger test development and epidemiology effort in Phase II. Phase II will focus on clinical testing, testing economics, and disease epidemiology in the context of HIV co-infection. The proposed system fills an important unmet need for improved POC syphilis testing, while at the same time establishing a platform for eventual multi-pathogen test rollout. The long term vision is a syphilis rapid test with parallel HIV testing in the same test cartridge. Such a system presents an opportunity for enormous cost savings in limited resource settings, where a multiplicity of manual, single-pathogen rapid tests will become costly and unwieldy.