IMPROVED ANTIGEN DETECTION TESTS FOR FILARIAL INFECTIONS

改进丝虫感染的抗原检测测试

• 批准号: 9509332
• 负责人: Philip Budge
• 金额: $ 17.34万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-01 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9509332
• 关键词: Adverse event; Adverse reactions; Africa; African; Antibodies; Antigens; Antiparasitic Agents; Applied Research; Area; Basic Science; Bedside Testings; Biological Assay; Biological Markers; Blood specimen; Central Africa; Certification; Cessation of life; Clinical Research; Communicable Diseases; Core Protein; Country; Detection; Development; Development Plans; Diagnosis; Diagnostic; Diagnostic tests; Disease; Dose; Drug usage; Encephalopathies; Environment; Epidemiology; Faculty; Filaria bancrofti; Filarial Elephantiases; Filariasis; Foundations; Funding; Future; Genes; Goals; Government; Human; Immunology; Individual; Industry; Infection; Internal Medicine; International; Interruption; Ivermectin; Knowledge; Laboratories; Loa; Loa loa; Loiasis; Mentors; Monitor; Monoclonal Antibodies; Nematoda; Onchocerciasis; Parasites; Parasitology; Patients; Persons; Pharmaceutical Preparations; Physicians; Population; Prevalence; Proteins; Public Health; Research; Research Personnel; Resources; Respiratory syncytial virus; Sampling; Scientist; Severe Adverse Event; Structure; Test Result; Testing; Time; Training; Translational Research; Universities; Washington; Work; World Health Organization; base; career; career development; cross reactivity; disability; experience; field study; global health; high risk; improved; neglected tropical diseases; novel; overtreatment; pathogen; programs; proteogenomics; public health intervention; public health research; research and development; skills; tool; transmission process; virology

PROJECT SUMMARY This project will identify and characterize biomarkers for human filarial infections and generate monoclonal antibodies against circulating filarial antigens that will be more specific than those used in current tests. The need for improved diagnostic tests is pressing at this time. The World Health Organization’s (WHO) Global Program to Eliminate Lymphatic Filariasis (GPELF) is rapidly moving towards its goal of global elimination of lymphatic filariasis (LF) by 2020. However, problems with diagnosis represent a major challenge to the program in Central Africa, where false positive results with the current filarial antigen tests may result in unnecessary and potentially harmful overtreatment of populations. Candidate I have more than 10 years of experience and training in biomedical, translational, and public health research. My doctoral studies on Respiratory Syncytial Virus gave me a broad understanding of principles of immunology, virology, and host-pathogen interactions. My more recent work in epidemiology has given me an appreciation of the scope and potential impact of global public health programs and of the critical importance of accurate diagnostic tools for public health programs and research. I am board certified in Internal Medicine with subspecialty certification as an Infectious Diseases clinician. This project supports my long-term career goal of becoming an independent investigator in the area of global infectious diseases with a focus on translational research of neglected tropical diseases; the project plan will also allow me to further develop my clinical research skills and knowledge of infectious diseases. Environment My surroundings at Washington University in St. Louis (WUSTL) are ideal for my proposed project and career development. The intellectual environment is outstanding and I intend to take advantage of this by completing a structured program of coursework focused on conducting field research in resource-poor settings. My mentor’s laboratory group has a tremendous amount of experience in basic and applied research in parasitology, and WUSTL is one of only a handful of research centers in the nation with strong expertise in filarial diseases. My mentor is the PI of the Death to Onchocerciasis and LF project (a large-scale global health project funded by the Bill and Melinda Gates Foundation), and has extensive expertise in parasitology, immunology, and international field research. This outstanding environment for filarial research was the reason I joined the WUSTL faculty in 2014. Research LF is one of the world’s leading causes of disability, and is one of a small number of infectious diseases that are potentially eradicable. WHO’s GPELF coordinates and supports the efforts of corporate, academic, governmental, and non-governmental partners to eliminate LF in 73 endemic countries through repeated cycles of mass drug administration (MDA) using industry-donated drugs. GPELF is the largest MDA-based public health intervention to date with more than 5.3 billion doses of antiparasitic medications distributed between 2000 and 2014 in 60 countries. Over 90% of the world’s LF burden (including all cases in Africa) is caused by the filarial nematode Wuchereria bancrofti (Wb), and all aspects of global elimination programs for bancroftian filariasis (mapping, MDA, surveillance, and verification) rely on diagnosis of LF using point-of-care tests that employ monoclonal antibodies to detect Wb circulating filarial antigen in blood samples. Recent studies have shown that these tests often produce falsely positive results with samples from people that are infected with Loa loa, a different filarial parasite that occurs in 11 countries in Central Africa. Inaccurate diagnostic test results can have serious or even fatal implications since drugs used in MDA for LF can cause serious adverse reactions (including encephalopathy and death) when taken by people with heavy L. loa infections. We hypothesize that falsely-positive filarial Wb antigen tests in patients with loiasis are due to the presence of a cross-reactive circulating L. loa antigen. This project aims to identify the circulating Loa antigen and develop assays that can distinguish the two infections. Improved diagnostic tests would significantly improve chances for control of loiasis and elimination of LF in the 11 Central African nations that have both of these diseases.

项目摘要 该项目将识别并表征人类丝状感染的生物标志物并产生单克隆 针对循环丝状抗原的抗体将比当前测试中使用的抗体更具体。这 此时，需要改进的诊断测试。世界卫生组织（WHO）全球 消除淋巴丝虫病（GPELF）的计划正在迅速朝着全球消除的目标迈进 到2020年，淋巴丝虫病（LF）。但是，诊断问题是对 中非的计划，在当前的丝状抗原测试中，假阳性结果可能会导致 人口的不必要且潜在的有害过度治疗。 候选人 我在生物医学，翻译和公共卫生研究方面拥有超过10年的经验和培训。 我关于呼吸综合病毒的博士研究使我对 免疫学，病毒学和宿主病原体相互作用。我最近在流行病学方面的工作给了我 对全球公共卫生计划的范围和潜在影响的欣赏以及至关重要的重要性 用于公共卫生计划和研究的准确诊断工具。我通过内科董事会认证 作为感染性疾病的亚科认证临床。这个项目支持我的长期职业目标 成为全球传染病领域的独立研究者，重点是翻译 研究被忽视的热带疾病；项目计划还可以使我进一步发展我的临床 研究技能和传染病知识。 环境 我在圣路易斯华盛顿大学（Wustl）的周围环境非常适合我拟议的项目和职业 发展。智力环境非常出色，我打算通过完成 一个结构化课程的课程，重点是在资源贫乏的环境中进行现场研究。我的 导师实验室小组在基础研究和应用研究方面具有丰富的经验 寄生虫学和Wustl是全国少数几个具有强大专业知识的研究中心之一 丝状疾病。我的心理是对OnChocerciasis和LF项目的死亡PI（全球大规模的全球健康状况 由Bill and Melinda Gates Foundation资助的项目），在寄生虫学方面拥有广泛的专业知识， 免疫学和国际现场研究。丝状研究的杰出环境是原因 我于2014年加入了Wustl教师。 研究 LF是世界上主要的主要原因之一，并且是少数传染病之一 可能是可放射的。谁的Gpelf协调并支持公司，学术， 政府和非政府合作伙伴通过反复反复消除73个内部人群的LF 大规模药物管理（MDA）的循环使用行业持有的药物。 Gpelf是最大的基于MDA的 迄今为止，分配了超过53亿剂的反寄生虫药物 在2000年至2014年之间，有60个国家 /地区。世界上有90％以上的LF伯恩（包括非洲的所有案件）是 由丝状线虫wucheria bancrofti（WB）以及全球消除计划的所有方面引起的 Bancroftian Filariasis（映射，MDA，监视和验证）依赖于LF的诊断方法 测试员工单克隆抗体以检测血液样本中循环丝状抗原的WB。最近的 研究表明，这些测试通常与来自 感染了LOA LOA，这是一种不同的丝状寄生虫，发生在中非的11个国家。不准确 诊断测试结果可能具有严重甚至是致命的影响，因为在MDA中用于LF的药物可能导致 当患有重LOA的人服用时，严重的不良反应（包括脑病和死亡） 感染。我们假设肺炎患者中错误阳性的丝质WB抗原测试是由于 存在交叉反应循环乳杆菌抗原。该项目旨在确定循环的LOA抗原 并开发可以区分两种感染的测定法。改进的诊断测试将显着 在11个具有两者 这些疾病。