Facile Detection of Soil-Transmitted Helminth Infections

描述（由申请人提供）：该项目的目标是开发一种快速准确的检测土壤传播蠕虫（STHs）的免疫诊断测试，可以在没有实验室基础设施的情况下使用。鞭虫（Trichuris）、蛔虫（Ascaris）和钩虫（Necator和anylostoma）引起的人类STH感染对全球公共卫生造成了重大负担。目前的感染率令人震惊，估计有超过10亿人至少携带其中一种线虫寄生虫，造成大量发病率。目前控制STH感染的全球战略涉及在没有事先诊断的情况下大量给药驱虫药。然而，治愈往往是不完全的，而且可用药物的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策略，临床研究活动也随之加强。其中包括监测耐药性的出现以及蠕虫感染对儿童生长发育的影响。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。目前所有的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识别寄生虫。最广泛使用的方法是显微镜检测寄生虫卵，这是一种劳动密集型技术，灵敏度和特异性不足。因此，在没有实验室基础设施或训练有素的人员的情况下，一种快速、敏感、特异和廉价的检测寄生虫感染的方法将比现有方法具有巨大的优势。基于密切相关寄生虫的广泛概念验证数据，本提案旨在开发一种检测人类STHs的免疫诊断方法。可行性的第一步将包括克隆、重组表达和生成抗血清来选择寄生虫靶点，随后是ELISA和寄生虫提取物和临床样本的western分析（第一阶段）。一旦提供足够敏感性和特异性的靶标得到验证，将开始进一步的分析优化、试剂扩展和多种流行病学环境评估（II期）。

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.