Facile Detection of Soil-Transmitted Helminth Infections

描述（由申请人提供）：本项目的目标是开发一种快速准确的免疫诊断试验，用于检测土壤传播蠕虫（STH），无需实验室基础设施即可使用。来自鞭虫（鞭虫属）、蛔虫（蛔虫属）和钩虫（钩虫属和钩虫属）的人类STH感染对全世界的公共卫生造成了巨大负担。 目前的感染率令人震惊，估计有超过10亿人携带至少一种此类线虫寄生虫，导致大量发病。 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大规模给药（MDA）驱虫药。 然而，治愈往往是不完全的，有限数量的可用药物引发了对寄生虫耐药性的担忧。 为了支持这一药物管理策略，临床研究活动同时加强。 其中包括监测抗药性的出现以及蠕虫感染对儿童生长和发育的影响。 尽管有这些需求，但没有商业产品来检测这些寄生虫。 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识别寄生虫物种。 最广泛使用的方法是寄生虫卵的显微镜检测，这是一种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，而无需实验室基础设施或训练有素的人员，将提供比现有方法更大的优势。 基于与密切相关的寄生虫的广泛概念验证数据，该提案旨在开发用于检测人类STH的免疫诊断测定。 走向可行性的第一步将涉及克隆、重组表达和产生抗血清以选择蠕虫靶标，然后用寄生虫提取物和临床样品进行ELISA和Western分析（I期）。 一旦验证了提供足够灵敏度和特异性的靶标，将开始进一步的检测优化、试剂扩增和多个流行病学环境的评价（II期）。 公共卫生相关性：土壤传播蠕虫（STH，蛔虫）目前感染全球超过10亿人，造成严重的发病率和经济损失。目前用于检测这些寄生虫的显微镜方法耗时，需要实验室基础设施，并且灵敏度差。 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药物管理计划的监测。

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.