Addressing the Global Burden of Leptospirosis in Two Endemic Countries

解决两个流行国家钩端螺旋体病的全球负担

• 批准号: 9225174
• 负责人: Joseph M. Vinetz
• 金额: $ 42万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2020-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9225174
• 关键词: Acute; Address; Affect; Affinity; Agriculture; Antibodies; Antigens; Area; Attention; Biological; Blood; Canis familiaris; Case Fatality Rates; Cattle; Centers for Disease Control and Prevention (U.S.); Clinical; Clinical Microbiology; Clinical Research; Collaborations; Communicable Diseases; Communities; Country; Culture Techniques; Databases; Deposition; Detection; Development; Diagnosis; Diagnostic; Diagnostic tests; Disease; Doctor of Philosophy; Environment; Enzyme-Linked Immunosorbent Assay; Epidemic; Epidemiology; Family suidae; Genbank; Generations; Genome; Geography; Goals; Gold; Human; Infection; International; Leptospira; Leptospirosis; Letters; Lipopolysaccharides; Marsupialia; Medicine; Methods; Microarray Analysis; Military Personnel; Molecular; Monoclonal Antibodies; Outcome; Outcomes Research; Outpatients; Pathogenicity; Peru; Protein Array; Protein Microchips; Proteins; Public Health; Publishing; Research; Risk; Rodent; Rural; Sampling; Serologic tests; Serum; Site; Source; Sri Lanka; Techniques; Testing; Thinking; Time; Translating; Translational Research; Translations; Urine; Water Buffalo; Work; World Health Organization; Zoonoses; base; burden of illness; clinically actionable; clinically relevant; direct application; disorder prevention; field study; follow-up; improved; novel strategies; prevent; programs; prospective; public health relevance; tool; transmission process

 DESCRIPTION (provided by applicant): The proposed U19 ICIDR Program is focused on human infection and disease by Leptospira. Our overall approach is to use fundamental biological scientific methods combined with clinical/field studies in contrasting epidemiological contexts in Peru and Sri Lanka, to develop new, clinically actionable diagnostic tests. Taking into account the local, regional, and international diversity of Leptospira, the proposed research addresses a hitherto insurmountable gap in the field, that of obtaining diagnostic tests for leptospirosis that are inexpensive, sensitive and efficient, yet easily deployable and effective regardless of the underlying transmission dynamics. The improved accuracy and efficiency of these tests will enable timely administration of appropriate therapy, which is vital for improving clinical outcomes. The overall goal of this Program is to develop robust tools and approaches that will effectively quantify the Global Burden of Leptospirosis, addressing several key goals shared by the international leptospirosis research community as articulated by the World Health Organization's Leptospirosis Epidemiology Reference Group (LERG).1, 2 These approaches, which are applicable to all leptospirosis-endemic and epidemic-prone sites, are summarized as follows: 1. Carry out prospective, field-based clinical studies of suspected acute leptospirosis cases in known or suspected highly endemic settings in Peru (Project 1) and Sri Lanka (Project 2) where the diversity of Leptospira is high and includes the most highly pathogenic as well as less pathogenic (but still infectious) Leptospira. These sites will include contrasting urban vs. rural and seasonal vs. perennial leptospirosis risk areas in Peru and Sri Lanka. The projects will focus on both hospitalized cases (more severe disease) and outpatients (generally mild spectrum of disease) with dedicated attention to comprehensively follow up clinical and microbiological/molecular outcomes; 2. Characterize serum and urine samples from field studies with regard to leptospirosis diagnosis using conventional serology (MAT, ELISA),3, 4, 5 routine culture, our published culture-independent molecular techniques (conventional PCR,6, 7 qPCR,8 Multi Locus Sequence Typing (MLST)9, 10); 3. Test newly developed antigen-detection tests (LPS; alternatively, Leptospira proteins) and antibody- based serological tests using protein microarray technology based on our newly developed Leptospira Genome Project database (PATRIC, http://patricbrc.org; deposited in GenBank, http://www.ncbi.nlm.nih.gov/bioproject/?term=leptospira (both accessed March 7, 2014)) against conventional diagnostics (gold standard re-defined as MAT (on paired samples) plus PCR of blood/urine, given the insensitivity of current culture techniques (problems with past gold-standard diagnostics discussed in Refs.11, 12). The expected outcomes of this program are 1) New tools to diagnose leptospirosis and to identify leptospiral infection of humans; 2) Define and optimize the generalizability of these new tools in diverse and representative settings in Peru and Sri Lanka, and beyond (for example, through the U.S. Centers for Disease Control and Prevention that receives samples from all over the world; see Renee Galloway, Letter of Support); and 3) Enhancing research capacity of foreign collaborators by facilitating development of independent creative scientific thinking, hypothesis generation and testing, and new approaches to addressing clinical and translational research problems of highest priority to the endemic country. Additional benefits from this project include clear application to OneHealth medicine because human leptospirosis reflects interactions of humans with zoonotic domestic and agricultural sources such as dogs, cattle, pigs, and water buffalo, wild and peridomestic rodents and marsupials. The tools developed here will have direct application and translation to veterinary and agricultural settings but such work will be beyond the scope of the present project.

 描述（由申请人提供）：诱导的U19 ICIDR计划侧重于人类感染和疾病。 H。解决该领域的杀伤差距，获得较便宜但易于部署且有效的诊断测试，无论测试的准确性和效率如何结果。 1。在（项目1）和斯里兰卡（Project 2）中，根据已知或怀疑高度流行的环境进行钩端螺旋体病病例，进行前瞻性，基于现场的关闭，其中钩端螺旋体的多样性很高，包括最高的病态，较少，并且更少这些地点（但仍然是感染性）将包括对比的城市与季节性与季节性与多年生Rosis风险区域的对比。疾病）专用于全面跟进临床和微生物学/分子成果； 2。将血清和尿液样品场表征为使用常规血清学（MAT，ELISA）诊断为链球菌病诊断，以发行的发行的培养物分子技术（常规PCR，6，7 QPCR，8个多基因座序列序列键入（MLST）9，10）; 3。测试新开发的抗原检测试验（LPS；替代性，钩端螺旋体蛋白）和基于抗体的血清学测试，该测试基于我们新开发的leptospira基因组项目数据库（Patric，http://patricbrc.org; rocked in Genbank; rocked in Genbank; ，http：//www.ncbi.nlm.nih.gov/bioproject/?term=reptospira（均为2014年3月7日访问））针对连接器（金标准ED作为垫子（配对样品）加上血/尿液/尿液的PCR，鉴于当前窗帘技术的铭文（参考文献1，第12期讨论的过去金标准诊断问题）。 工具工具的预期结果工具诱因，并识别人类的钩端螺旋体感染；通过促进独立创造性的科学思维和测试的研究，以及针对特有国家的最高优先研究的新方法，是对人类诱发的项目的应用程序。狗，牛，猪和水牛，野生和围产的啮齿动物和有袋动物。