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Rapid Sample-to-Answer Diagnosis of Kaposi's Sarcoma Across Sub-Saharan Africa using KS-COMPLETE

使用 KS-COMPLETE 对撒哈拉以南非洲地区的卡波西肉瘤进行快速样本到答案诊断

基本信息

批准号：
10416778
负责人：
ETHEL CESARMAN
金额：
$ 65.74万
依托单位：
CORNELL UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-06-10 至 2027-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10416778
关键词：
Address Adoption Africa Africa South of the Sahara African Biopsy Clinical Communicable Diseases DNA Dermatology Detection Development Diagnosis Diagnostic Diagnostic Procedure Diagnostic tests Discipline Early Diagnosis Engineering Enrollment Epidemiology Evaluation Exclusion Genes Goals Histopathology Hour Human Human Herpesvirus 8 Immunohistochemistry Indiana Infrastructure Institutes Kaposi Sarcoma Lead Malignant Neoplasms Manuals Medicine Methods Multi-Institutional Clinical Trial Nature Nucleic Acids Outcome Pathologist Pathology Patient-Focused Outcomes Patients Phase Physicians Point of Care Technology Point-of-Care Systems Positioning Attribute Process Punch Biopsy Research Rwanda Sampling Sensitivity and Specificity Series Site Skin Solid System Tanzania Techniques Technology Time Training Uganda Universities Validation Viral Woman Work accurate diagnosis base chemotherapy clinical efficacy clinical research site cost diagnostic platform field study improved low and middle-income countries men mycobacterial operation point of care point-of-care diagnosis point-of-care diagnostics prevent professor prototype rapid diagnosis skin disorder tumor uptake

项目摘要

Abstract In this proposal, we will develop, manufacture, and perform a multi-site sub-Saharan African clinical validation of KS-COMPLETE — the first true point-of-care sample-to-answer diagnostic system for Kaposi's sarcoma (KS). Our recent large-scale studies in Africa have shown that KS can be diagnosed through quantification of Kaposi's sarcoma herpesvirus (KSHV) DNA in a skin biopsy with high sensitivity and specificity. These efforts have also resulted in the development of TINY — a robust, easy-to-use, infrastructure-free, point- of-care (PoC) technology for KSHV DNA quantification — which is being currently deployed in a multi-site evaluation. The work has also revealed that the key challenge to widespread adoption of skin biopsy-based PoC systems is the time and manual steps required to extract DNA from a skin biopsy — which can be up to 4 hours. KS-COMPLETE will be the first “direct-to-LAMP” diagnostic system for skin punch biopsies. Similar direct-to-LAMP methods have greatly simplified PoC diagnostics for other sample matrices but the solid-phase, collagenous nature of skin has made this a challenge for biopsies. KS-COMPLETE will address this issue with our “SLICER” technology that will automatically process a punch biopsy into smaller “micro-cores” on which we can directly perform DNA quantification in TINY through our “direct-to-LAMP” approach. This approach will reduce the time to result to around 60 minutes, eliminate all the current manual and intensive sample processing steps, and is compatible with cost, robustness, infrastructure, and simplicity requirements for operation in LMICs. Clinical validation of the system will be done through our established network of KS clinical sites in Africa. By the end of the project, we will deliver 12 KS-Complete systems and conduct a multi-site clinical validation. KS is one of the most common cancers in men and women in sub-Saharan Africa. KS is difficult to distinguish from other skin conditions, particularly in Africa where access to trained pathologists is limited and immunohistochemistry is practically non-existent. Early-stage and more accurate diagnosis would confer many clinical benefits. For patients who have KS, it obviates the need for the difficult to obtain, slow, and unreliable histopathology and allows for detection at earlier clinical stages resulting in better clinical outcomes. For patients with mimickers, rapid exclusion of KS allows for timely re-orienting of the diagnostic process and prevents use of potentially toxic chemotherapy. Our direct-to-LAMP diagnostic test could have significant impact beyond the diagnosis of KS as multiple other viral, mycobacterial and fungal-related skin diseases currently diagnosed through traditional pathology could be transitioned to this method and ultimately the point of care.

抽象的在本提案中，我们将开发、制造和执行撒哈拉以南非洲的多地点临床 KS-COMPLETE 的验证——第一个真正的现场护理样本到答案诊断系统卡波西肉瘤（KS）。我们最近在非洲进行的大规模研究表明，KS 可以通过以下方式诊断：以高灵敏度和特异性对皮肤活检中的卡波西肉瘤疱疹病毒 (KSHV) DNA 进行定量。这些努力还导致了 TINY 的开发——一个强大的、易于使用的、无基础设施的、点对点的用于 KSHV DNA 定量的护理 (PoC) 技术 — 目前正在多个站点部署评估。这项工作还揭示了广泛采用基于皮肤活检的 PoC 的关键挑战系统是从皮肤活检中提取 DNA 所需的时间和手动步骤 - 可能长达 4 小时。 KS-COMPLETE 将是第一个用于皮肤穿刺活检的“直接到 LAMP”诊断系统。相似的直接 LAMP 方法极大地简化了其他样品基质的 PoC 诊断，但固相、皮肤的胶原性质使得这对活检来说是一个挑战。 KS-COMPLETE 将解决这个问题我们的“SLICER”技术将自动将打孔活检处理成更小的“微核”，我们可以在其上可以通过我们的“direct-to-LAMP”方法直接在 TINY 中进行 DNA 定量。这种方法将将获得结果的时间缩短至 60 分钟左右，消除当前所有手动和密集的样品处理步骤，并且符合中低收入国家运营的成本、稳健性、基础设施和简单性要求。该系统的临床验证将通过我们在非洲建立的 KS 临床站点网络进行。经过项目结束时，我们将交付 12 个 KS-Complete 系统并进行多站点临床验证。 KS 是撒哈拉以南非洲地区男性和女性最常见的癌症之一。 KS很难区分来自其他皮肤状况，特别是在非洲，那里受过训练的病理学家的接触机会有限，免疫组织化学几乎不存在。早期和更准确的诊断将赋予许多临床益处。对于患有 KS 的患者来说，它消除了对难以获得、缓慢且不可靠的需求组织病理学，并允许在早期临床阶段进行检测，从而获得更好的临床结果。对于患者通过模仿者，快速排除 KS 可以及时重新定位诊断过程并防止使用潜在有毒的化疗。我们的直接 LAMP 诊断测试可能会产生超出预期的重大影响将 KS 诊断为目前诊断的多种其他病毒、分枝杆菌和真菌相关皮肤病通过传统病理学可以过渡到这种方法并最终过渡到护理点。