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

• 批准号: 10642906
• 负责人: ETHEL CESARMAN
• 金额: $ 61.26万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 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/10642906
• 关键词: 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; Kaposi Sarcoma; 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; Qualifying; Research; Rwanda; Sampling; Sensitivity and Specificity; Series; Site; Skin; Solid; System; Tanzania; Techniques; Technology; Time; Training; Uganda; Universities; Validation; Viral; Woman; Work; accurate diagnosis; chemotherapy; clinical efficacy; clinical research site; cost; diagnostic platform; field study; improved; low and middle-income countries; manufacture; men; mycobacterial; operation; point of care; point-of-care diagnosis; point-of-care diagnostics; prevent; professor; prototype; rapid diagnosis; skin disorder; tumor; uptake

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 我们最近在非洲进行的大规模研究表明，卡波西肉瘤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 的发展——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 这项评估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 LAMP”诊断系统。 直接 LAMP 方法极大地简化了除固相、 皮肤的胶原性质使这成为活检的一个挑战，KS-COMPLETE 将解决这个问题。 我们的“SLICER”技术将自动将打孔活检加工成更小的“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。 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。 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。 免受其他皮肤病的影响，特别是在非洲，那里受过训练的病理学家的接触机会有限， 免疫组织化学实际上是不存在的，早期和更准确的诊断将给予许多人。 对于 KS 患者来说，它消除了难以获得、缓慢且不可靠的需要。 组织病理学并允许在早期临床阶段进行检测，从而为患者带来更好的临床结果。 通过模仿者，快速排除 KS 可以及时重新调整诊断过程并防止使用 我们的直接 LAMP 诊断测试可能会产生超越化疗的重大影响。 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。