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A strategy for point-of-care molecular detection of parasitic helminth infections

寄生虫感染的即时分子检测策略

基本信息

批准号：
8847651
负责人：
ROBERT M GREENBERG
金额：
$ 20万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-05-09 至 2016-10-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8847651
关键词：
Animal Model Anthelmintics Area Attention Biological Assay Biological Markers Culicidae DNA Detection Developing Countries Development Devices Diagnosis Diagnostic Diagnostic Procedure Disease Drug resistance Economic Development Encapsulated Environment Equipment Evaluation Failure Filariasis Funding Goals Hand Health Helminths Human Human Resources Infection Infection Control Lead Legal patent Liquid substance Mediating Membrane Methodology Methods MicroRNAs Microfluidic Microchips Molecular Molecular Diagnosis Molecular Target Monitor Nematoda Nucleic Acid Amplification Tests Nucleic Acids Parasites Parasitic infection Pharmaceutical Preparations Plastics Population Prevalence RNA RNA Sequences Reagent Research Infrastructure Research Priority Resources Reverse Transcription Sampling Schistosoma Schistosomiasis Sensitivity and Specificity Serum Site Snails Soil Specificity Staging Technology Testing Tissues Training Training and Infrastructure Translating Translations Treatment Efficacy Treatment Failure Vaccines Work World Health Organization amplification detection chemotherapy circulating microRNA disease transmission effectiveness measure health economics helicase improved neglected tropical diseases new technology nucleic acid purification point of care programs rapid diagnosis research study success tool transcriptome sequencing transmission process treatment strategy

项目摘要

DESCRIPTION (provided by applicant): Parasitic helminths such as schistosomes and filarial and soil-transmitted nematodes are estimated to infect at least a billion people worldwide, with huge impacts on human health and economic development. In the absence of vaccines, treatment and control of these neglected tropical diseases relies in large part on a small set of anthelmintic drugs. However, diagnosis and monitoring of disease transmission and efficacy of treatment depends almost entirely on methods that are inaccurate, labor-intensive, and unreliable. These limitations are amplified and take on added significance in mass drug administration programs, where measures of effectiveness depend on the ability to accurately monitor treatment success (or failure), changes in disease transmission rates, and emergence of drug resistance. Molecular methods for detection and quantitation of parasite nucleic acids in host fluids or tissues offer reliability, sensitivity, and specificity, but depend on availability f necessary infrastructure, highly-trained staff, and expensive and delicate equipment. The long-term goal of this exploratory project is to overcome these limitations. To do so, we will adapt isothermal molecular assays such as loop-mediated isothermal amplification (LAMP) to a simple, hand-held, point-of-care microfluidic device that allows sensitive and specific detection of helminth parasite nucleic acids in infected hosts. We will use animal models of parasitic helminth infection to demonstrate the feasibility of this technology and as proof of principle. Use of such a device could provide critical advancements in diagnostics, monitoring of disease prevalence and treatment efficacy in mass drug administration programs, and detection of treatment failures that might warrant attention as signs of emerging drug resistance. The specific aims are to: 1) Optimize isothermal amplification assays of helminth nucleic acids in samples from parasite-infected hosts~ and 2) Develop and demonstrate the feasibility of a simple nucleic acid amplification test for parasitic helminths in a point-of-care device format. Translation of this type of simple, inexpensive, self-contained technology for detection of parasitic helminth nucleic acids in hosts or in the environment could ultimately transform analysis of treatment and control options in the developing world.

描述（由申请人提供）：寄生蠕虫，如寄生虫、丝虫和土传线虫，估计感染全球至少10亿人，对人类健康和经济发展产生巨大影响。在没有疫苗的情况下，这些被忽视的热带疾病的治疗和控制在很大程度上依赖于一小套驱虫药物。然而，疾病传播的诊断和监测以及治疗效果几乎完全取决于不准确、劳动密集型和不可靠的方法。这些局限性在大规模药物管理计划中被放大并具有额外的意义，其中有效性的措施取决于准确监测治疗成功（或失败），疾病传播率变化和耐药性出现的能力。用于检测和定量宿主体液或组织中寄生虫核酸的分子方法提供可靠性、灵敏度和特异性，但依赖于必要的基础设施、训练有素的工作人员和昂贵且精密的设备的可用性。这个探索性项目的长期目标是克服这些限制。要做到这一点，我们将适应等温分子检测，如环介导等温扩增（LAMP），以一个简单的，手持的，即时的微流控装置，允许敏感和特异性检测蠕虫寄生虫核酸感染的主机。我们将使用寄生蠕虫感染的动物模型来证明这种技术的可行性，并作为原理的证明。使用这种设备的使用可以在诊断、监测疾病流行和大规模药物管理计划中的治疗效果以及检测可能作为新出现的耐药性迹象而值得关注的治疗失败方面提供关键的进步。具体目标是：1）优化寄生虫感染宿主样本中蠕虫核酸的等温扩增试验，2）开发并证明以即时设备形式进行寄生虫核酸扩增试验的可行性。将这种简单、廉价、独立的技术用于检测宿主或环境中的寄生蠕虫核酸，最终可能会改变发展中国家的治疗和控制选择分析。