Facile Detection of Soil-Transmitted Helminth Infections

描述(申请人提供)：该项目的目标是开发一种快速和准确的免疫诊断测试，用于检测土传蠕虫(STH)，无需实验室基础设施即可使用。鞭虫(鞭虫)、蛔虫(蛔虫)和钩虫(死虫和钩虫)对人类STH的感染给全球公共卫生造成了巨大的负担。目前的感染率令人震惊，估计有超过10亿人携带至少一种线虫寄生虫，导致相当大的发病率。目前控制STH感染的全球战略包括在没有事先诊断的情况下对驱虫药进行大规模给药(MDA)。然而，治愈往往并不完全，可用的药物数量有限加剧了人们对寄生虫耐药性的担忧。为了支持这一药物管理战略，临床研究活动同时加强。这些措施包括监测耐药性的出现和蠕虫感染对儿童生长和发育的影响。尽管有这些需求，但目前还没有检测这些寄生虫的商业产品。目前的所有诊断方法都需要使用实验室设备和经过临床培训的人员来鉴定寄生虫物种。最广泛使用的方法是寄生虫卵的显微检测，这是一项灵敏度和特异性不足的劳动密集型技术。因此，一种快速、灵敏、特异和廉价的方法来检测寄生虫感染，而不需要实验室基础设施或训练有素的人员，将比目前的方法提供巨大的优势。基于大量与寄生虫密切相关的概念验证数据，这项建议旨在开发一种检测人类STH的免疫诊断方法。迈向可行性的第一步将包括克隆、重组表达和产生抗血清以选择蠕虫靶标，然后是用寄生虫提取物和临床样本进行ELISA法和蛋白质分析(第一阶段)。一旦提供足够灵敏度和特异度的靶标得到验证，将开始进一步的分析优化、试剂扩展和对多种流行病学环境的评估(第二阶段)。 公共卫生相关性：土壤传播的蠕虫(性传播蠕虫、蛔虫)目前感染全球10多亿人，造成大量发病率和经济损失。目前用于检测这些寄生虫的显微镜方法耗时长，需要实验室基础设施，而且灵敏度较低。该项目的目标是开发一种快速、准确的STH感染免疫诊断测试，以支持患者管理、流行病学研究和大规模用药项目的监测。

DESCRIPTION (provided by applicant): The goal of this project is to develop a rapid and accurate immunodiagnostic test for detection of soil- transmitted helminths (STHs) that can be used without laboratory infrastructure. Human STH infections from whipworm (Trichuris), roundworm (Ascaris), and hookworms (Necator and Ancylostoma) create a substantial burden to worldwide public health. Current infection rates are staggering, with well over one billion people estimated to be harboring at least one of these nematode parasites, causing substantial morbidity. The current global strategy to control STH infections involves mass drug administration (MDA) of anthelmintic medicines without prior diagnosis. However, cure is often not complete and the limited number of available drugs has fueled concerns of parasite resistance. To support this drug administration strategy, clinical research activities have concurrently intensified. These include monitoring for the emergence of drug resistance and the effects of worm infection on childhood growth and development. Despite these needs, no commercial product to detect these parasites is available. All current diagnostic methods require the use of laboratory equipment and clinically trained personnel to identify parasitic species. The most widely-used method is the microscopic detection of parasite eggs, a labor-intensive technique with inadequate sensitivity and specificity. Therefore a rapid, sensitive, specific, and inexpensive method to detect parasitic worm infections without laboratory infrastructure or trained personnel would offer enormous advantages over current methods. Building upon extensive proof-of-concept data with closely related parasites, this proposal aims to develop an immunodiagnostic assay for detection of human STHs. The first step toward feasibility will involve cloning, recombinant expression, and generation of antiserum to select helminth targets, followed by ELISA and western analyses with parasite extracts and clinical samples (Phase I). Once targets providing adequate sensitivity and specificity are validated, further assay optimization, expansion of reagents, and evaluation of multiple epidemiologic settings will commence (Phase II). PUBLIC HEALTH RELEVANCE: Soil-transmitted helminths (STHs, roundworms) currently infect over one billion people globally, causing substantial morbidity and economic loss. The current microscopic method for detecting these parasites is time-consuming, requires laboratory infrastructure, and suffers from poor sensitivity. The goal of this project is to develop a rapid and accurate immunodiagnostic test for STH infections in support of patient management, epidemiologic studies, and surveillance of mass drug administration programs.