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: 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
• 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

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.

摘要