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Assay for Detection of Loxosceles Envenomation

斜索蛇毒的检测测定

基本信息

批准号：
7405490
负责人：
WILLIAM V STOECKER
金额：
$ 11.19万
依托单位：
STOECKER & ASSOCIATES
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-09-01 至 2009-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7405490
关键词：
Accident and Emergency department Address Affinity American Animals Antibodies Antibody Formation Area Arthropod Venoms Arthropods Binding Biological Assay Bioreactors Bite Cessation of life Clinical Clinical Research Color Condition Contralateral Country Cutaneous Detection Development Device Approval Diagnosis Diagnostic Diagnostic tests Differential Diagnosis Economics Enzyme-Linked Immunosorbent Assay Facility Construction Funding Category Goals Human Hybridomas In Vitro Infectious Skin Diseases Inflammation Mediators Lateral Lesion Libraries Life Marketing Measures Modeling Monoclonal Antibodies Morbidity - disease rate Necrosis Oryctolagus cuniculus Painless Patients Phase Physicians Preparation Printing Production Proteins Public Health Reagent Research Saline Sampling Sensitivity and Specificity Site Skin Skin Cancer Source Specificity Specimen Spider Bites Spider Venoms Spiders Standards of Weights and Measures Surface Surveys Swab Techniques Testing Time Triplet Multiple Birth Tube United States United States Food and Drug Administration Venoms Week Work clinical application commercialization cross reactivity crosslink day in vivo loxosceles venom mortality polyclonal antibody prototype research clinical testing satisfaction sphingomyelin phosphodiesterase D tool wound

项目摘要

DESCRIPTION (provided by applicant): Envenomations by the brown recluse spider, Loxosceles reclusa, are a significant source of morbidity in endemic regions of the United States, and misdiagnoses are common. A survey of physicians in the endemic area has shown the economic viability of an accurate diagnostic test for these spider bites. Development and testing of an optimized Loxosceles venom assay will present significant challenges. Unlike the routine construction of ELISAs dedicated to the detection of a single protein, this ELISA will detect venom containing multiple proteins, including a unique physiologically active protein- sphingomyelinase D (SMD) abundantly present in the venom. In preliminary research, our polyclonal assay has shown good sensitivity and good in- vitro specificity. Our research shows that identifiable amounts of venom in clinical envenomations are present for at least seven days. In rabbits, our polyclonal assay allows identification of venom on the surface for as long as two weeks. The limits of sensitivity, in-vivo specificity, and the duration of detection are unknown. Phase I should allow both determination of the smallest amount of venom detectable as well as the clinical time limits for in-vivo duration of sensitivity and specificity of the assay. Monoclonal antibodies will be isotyped and quantities raised in a bioreactor to perform checkerboard analysis. This analysis will allow determination of an optimal combination of L. reclusa monoclonal and polyclonal antibodies. A kit assay will result from Phase I, allowing multi-site testing in Phase II. These clinical studies will allow development of a lateral flow assay or microtiter plate assay, with the goal of FDA device approval and marketing. Clinical application of an optimized assay would save the morbidity and expense due to inappropriate diagnosis and treatment of various skin conditions with presentations similar to Loxosceles envenomations. Techniques used in the successful detection of this spider venom are directly applicable to bites from S. American Loxosceles species, responsible for additional deaths each year. The swab venom assay technique could be applicable to envenomations from numerous species. PUBLIC HEALTH RELEVANCE: Bite of the brown recluse spider Loxosceles recluse, cause considerable morbidity and occasional mortality in the Midwest. Many lesions can appear similar and mimic spider bites, including bacterial and fungal skin infections as well as skin cancer. The goal of this project is to develop a commercially viable test for brown recluse spider bites using a painless and simple swab test for the spider venom on the surface of the skin.

描述(由申请人提供)：棕色隐居蜘蛛的毒液是美国流行地区发病率的重要来源，误诊很常见。对疫区医生的调查表明，对这些蜘蛛叮咬进行准确的诊断测试在经济上是可行的。开发和测试一种优化的毒液检测方法将带来巨大的挑战。与用于检测单一蛋白质的常规ELISA构建不同，该ELISA将检测包含多种蛋白质的蛇毒，包括丰富存在于蛇毒中的一种独特的生理活性蛋白质-鞘磷脂酶D(SMD)。在初步研究中，我们的多克隆试验显示了良好的敏感性和体外特异性。我们的研究表明，临床毒液中可识别的毒液数量至少存在七天。在兔子身上，我们的多克隆检测方法可以在长达两周的时间内鉴定出表面的毒液。敏感度、体内特异度和检测时间的界限尚不清楚。第一阶段应允许确定可检测到的最小毒液数量以及体内检测灵敏度和特异度的临床时限。将对单抗进行同型，并在生物反应器中培养数量以进行棋盘分析。通过这种分析，可以确定雷氏乳杆菌单抗和多克隆抗体的最佳组合。第一阶段将产生试剂盒测试，允许在第二阶段进行多点测试。这些临床研究将允许开发侧向流动测试或微滴定板测试，目标是FDA设备批准和上市。临床应用一种优化的检测方法将节省由于对各种皮肤疾病不适当的诊断和治疗而导致的发病率和费用，这些皮肤疾病的表现类似于粘液中毒。成功检测这种蜘蛛毒液所用的技术直接适用于被美洲毒液杆菌叮咬的物种，这种毒液每年造成额外的死亡。拭子毒液检测技术可适用于多种种类的毒液。与公共卫生相关：被棕色隐士蜘蛛咬伤，在中西部地区会导致相当大的发病率和偶尔的死亡。许多皮损看起来与蜘蛛咬伤相似，包括细菌和真菌皮肤感染以及皮肤癌。该项目的目标是开发一种商业上可行的棕色隐士蜘蛛叮咬测试，使用一种无痛和简单的拭子测试皮肤表面的蜘蛛毒液。

项目成果

期刊论文数量（5）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Extreme pain from brown recluse spider bites: model for cytokine-driven pain.

棕色隐士蜘蛛咬伤引起的极度疼痛：细胞因子驱动的疼痛模型。

DOI：
10.1001/jamadermatol.2014.605
发表时间：
2014
期刊：
JAMA dermatology
影响因子：
10.9
作者：
Payne,KatieS;Schilli,Karen;Meier,Katlyn;Rader,RyanK;Dyer,JonathanA;Mold,JamesW;Green,JonathanA;Stoecker,WilliamV
通讯作者：
Stoecker,WilliamV

Diagnosis of loxoscelism in a child confirmed with an enzyme-linked immunosorbent assay and noninvasive tissue sampling.

通过酶联免疫吸附测定和非侵入性组织取样证实了一名儿童的异侧弯曲症的诊断。