Non-invasive detection of malaria parasites in vitro and in Cameroonian adults

体外和喀麦隆成年人体内疟原虫的无创检测

• 批准号: 10373306
• 负责人: SUNIL PARIKH
• 金额: $ 24.51万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-25 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10373306
• 关键词: Acoustics; Address; Adult; Adverse event; African; Age; Agreement; Animal Model; Area Under Curve; Biological Assay; Blood; Blood Circulation; Blood Vessels; Blood specimen; Cameroon; Cells; Characteristics; Child; Clinical; Collection; Computer Analysis; Computer software; Coupled; Crystallization; Data; Detection; Development; Devices; Diagnostic Procedure; Diagnostic tests; Ensure; Evaluation; Exhibits; Falciparum Malaria; Fever; Flow Cytometry; Gene Deletion; Gold; Heme; Human; In Vitro; Individual; Infection; Infrastructure; Investigation; Iron; Knowledge; Label; Laboratories; Lasers; Lead; Life Cycle Stages; Location; Longitudinal Studies; Malaria; Malaria Diagnosis; Malaria Diagnostic; Melanoma Cell; Metabolism; Methods; Microscopy; Molecular; Morbidity - disease rate; Mus; Non-Invasive Cancer Detection; Parasitemia; Parasites; Participant; Performance; Peripheral; Phagocytes; Pharmacodynamics; Pigmentation physiologic function; Plasmodium; Plasmodium falciparum; Plasmodium vivax; Pregnant Women; Property; Rapid diagnostics; Receiver Operating Characteristics; Reverse Transcriptase Polymerase Chain Reaction; Safety; Shapes; Signal Transduction; Skin; Slide; Techniques; Testing; Undifferentiated; Variant; absorption; base; cell type; cost; density; detection limit; follow-up; hemozoin; human data; in vivo; light microscopy; malaria infection; melanoma; molecular diagnostics; mortality; novel; pathogen; patient screening; point of care; portability; prospective; prototype; rapid detection; safety assessment; sample collection; secondary outcome; tool; ultrasound

Project Summary Malaria remains the leading infectious cause of morbidity and mortality by a single pathogen in sub-Saharan African children despite great progress in the past two decades. While the advent of rapid diagnostic tests has been a major stride, these tests suffer from similarly inadequate sensitivity as the gold standard, microscopy, and require a blood sample for testing. Newer molecular methods offer enhanced sensitivity, but most require significantly higher levels of laboratory infrastructure, cost more, and take longer to perform than microscopy and rapid diagnostic tests. Photoaccoustic flow cytometry (PAFC) is a technique that allows for the non- invasive detection of various cell types based on photoaccoustic signals generated following laser absorption. The device is being used currently in melanoma trials in humans and has demonstrated excellent safety. We have pioneered its use for the non-invasive detection of malaria in laboratory settings, as well as in animal models, and have demonstrated safety in early human studies using a portable prototype. As a follow-up, we propose to rigorously assess the in vivo analytical performance of this portable prototype for the detection of uncomplicated Plasmodium falciparum malaria in adults in Cameroon. PAFC results will be compared to highly sensitive and specific molecular assays, alongside standard diagnostic methods. Importantly, participants will be studied longitudinally, and rigorous safety assessments will be conducted. As a second aim, we will determine the ability of PAFC to detect and distinguish human malaria species in vitro and ex vivo through the use of stored blood from infected individuals, in vitro culture, and microscopy slides. Overall, the proposed studies aim to demonstrate the rapid, safe, and highly sensitive capability of PAFC for the non-invasive detection of malaria in non-pregnant adults. Data will lay the groundwork for expanded studies by our group in children, pregnant women, severe malaria patients, screening of asymptomatic individuals, and additional pharmacodynamic studies.

项目摘要 疟疾仍然是撒哈拉以下病原体发病和死亡率的主要传染病 非洲儿童尽管在过去的二十年中取得了长足的进步。快速诊断测试的出现 这些测试是主要的大步，与金标准相似的灵敏度不足，显微镜，显微镜， 并需要血液样本进行测试。较新的分子方法具有增强的灵敏度，但大多数需要 实验室基础设施的水平明显更高，成本更高，并且比显微镜需要更长的时间。 和快速诊断测试。光导流式细胞仪（PAFC）是一种允许非 - 基于激光吸收后产生的光门信号对各种细胞类型的侵入性检测。 该设备目前正在人类的黑色素瘤试验中使用，并且显示出极好的安全性。我们 在实验室环境中以及动物中的非侵入性检测率开创了其用于疟疾的无创使用 模型，并使用便携式原型证明了早期人类研究的安全性。作为后续行动，我们 建议严格评估该便携式原型的体内分析性能以检测 喀麦隆成年人的恶性疟疾疟原虫疟原虫疟原虫。 PAFC结果将与高度比较 敏感和特定的分子测定，以及标准诊断方法。重要的是，参与者会 纵向研究，将进行严格的安全评估。作为第二个目标，我们将 确定PAFC通过体外检测和区分人类疟疾物种的能力 使用感染者，体外培养和显微镜幻灯片的储存血液。总体而言，提议 研究旨在证明PAFC对于非侵入性的快速，安全和高度敏感的能力 在非妊娠成年人中检测疟疾。数据将为我们小组的扩大研究奠定基础 儿童，孕妇，严重的疟疾患者，无症状患者的筛查以及额外 药效研究。