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: 10613484
• 负责人: SUNIL PARIKH
• 金额: $ 19.44万
• 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/10613484
• 关键词: Acoustics; Address; Adult; Adverse event; African; Age; Agreement; Animal Model; Area Under Curve; Biological Assay; Blood; Blood Vessels; Blood specimen; Cameroon; Cells; Characteristics; Child; Circulation; Clinical; Collection; Computer Analysis; Computer software; Coupled; Data; Detection; Development; Devices; Diagnostic Procedure; Diagnostic tests; Ensure; Evaluation; Exhibits; Falciparum Malaria; Fever; Flow Cytometry; Gene Deletion; 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 Detection; Parasitemia; Parasites; Participant; Patients; Penetration; Performance; Peripheral; Phagocytes; Pharmacodynamics; Pigmentation physiologic function; Plasmodium; Plasmodium falciparum; Plasmodium vivax; Pregnant Women; Property; Quantitative Reverse Transcriptase PCR; Rapid diagnostics; Receiver Operating Characteristics; Reverse Transcriptase Polymerase Chain Reaction; Safety; Shapes; Signal Transduction; Skin; Slide; Techniques; Testing; Undifferentiated; Variant; absorption; cell type; cost; detection limit; follow-up; hemozoin; human data; in vivo; light microscopy; malaria infection; melanoma; molecular diagnostics; mortality; novel; pathogen; point of care; portability; prospective; prototype; rapid detection; safety assessment; sample collection; screening; 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.

项目概要 疟疾仍然是撒哈拉以南地区单一病原体发病和死亡的主要原因 尽管非洲儿童在过去二十年取得了巨大进步。虽然快速诊断测试的出现 虽然这是一个重大进步，但这些测试与金标准、显微镜、 并需要血液样本进行测试。较新的分子方法提供了更高的灵敏度，但大多数都需要 与显微镜相比，实验室基础设施水平明显更高，成本更高，执行时间更长 和快速诊断测试。光声流式细胞术 (PAFC) 是一种允许非 基于激光吸收后产生的光声信号对各种细胞类型进行侵入性检测。 该设备目前正在人体黑色素瘤试验中使用，并表现出出色的安全性。我们 率先将其用于实验室环境以及动物中的疟疾非侵入性检测 模型，并在早期人体研究中使用便携式原型证明了安全性。作为后续行动，我们 建议严格评估这种便携式原型的体内分析性能，以检测 喀麦隆成人中无并发症的恶性疟原虫疟疾。 PAFC 结果将与高度 敏感且特异的分子检测以及标准诊断方法。重要的是，参与者将 进行纵向研究，并进行严格的安全评估。作为第二个目标，我们将 确定 PAFC 通过以下方法在体外和离体检测和区分人类疟疾种类的能力 使用来自受感染个体的储存血液、体外培养物和显微镜载玻片。总体而言，建议 研究旨在证明 PAFC 用于非侵入性检测的快速、安全和高度灵敏的能力 在非怀孕成人中检测疟疾。数据将为我们小组的扩展研究奠定基础 儿童、孕妇、重症疟疾患者、无症状个体筛查等 药效学研究。