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Clinical Evaluation of Direct LDMS for Malaria Diagnosis in Humans

机译:人类疟疾疟疾诊断的临床评价

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Rapid and high throughput methods for detection of malaria in blood have become indispensable for the effective treatment and control of this disease. While optical microscopy of blood smears is still the "gold standard", new diagnostic tools are being developed to improve repeatability in the field, to improve sensitivity and to produce higher-throughput capability. Direct LDMS was utilized recently for quantitative detection of malaria parasites in blood, both in vitro and in vivo [1-5]. The method is based on detection of heme as malaria-specific biomarker [1]. In infected erythrocytes, the malaria parasite sequesters heme (iron protoporphyrin IX) from digested hemoglobin in a molecular crystal called hemozoin (Hz), a unique evolutionary feature of Plasmodium designed to counter the toxic effects of the unbound heme. Thus, the parasite itself creates a volume of highly concentrated and purified biomarker molecules (the end product of the parasite's intraerythrocytic metabolism), uniquely suited for sensitive and specific detection of malaria by LDMS. The assay is easy to perform: diluted peripheral blood is deposited on a slide and then automatically analyzed in a LDMS TOF instrument. Here LDMS results from several blind clinical studies involving human patients are presented and compared to microscopy and PCR-based diagnosis.
机译:用于检测血液中疟疾的快速和高通量方法对于这种疾病的有效治疗和控制具有必不可少的方法。虽然血液涂片的光学显微镜仍然是“黄金标准”,但正在开发新的诊断工具以提高现场的可重复性,以提高灵敏度并产生更高通量的能力。最近利用直接LDMS用于定量检测血液中的疟疾寄生虫,体外和体内[1-5]。该方法基于血红素作为疟疾特异性生物标志物的检测[1]。在受感染的红细胞中,疟疾寄生虫寄生术中的血红素(铁原卟啉IX),其中分子晶体中被消化的血红蛋白(Hz),疟原虫的独特进化特征,设计用于对抗未结血红素的毒性作用。因此,寄生虫本身产生高度浓缩和纯化的生物标志物分子(寄生虫的嗜鼻细胞新代谢的最终产物),唯一适用于LDMS的敏感和特异性检测疟疾。测定易于表现:稀释的外周血沉积在载玻片上,然后在LDMS TOF仪器中自动分析。此处提出了涉及人类患者的几项盲临床研究的LDM,并与显微镜和基于PCR的诊断相比。

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