Developing Diagnostics for Assessing Leptospirosis Burden of Disease in Sri Lanka

开发评估斯里兰卡钩端螺旋体病疾病负担的诊断方法

• 批准号: 9225180
• 负责人: Suneth Buddhika Agampodi
• 金额: $ 9.23万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-03-01 至 2020-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9225180
• 关键词: Activities of Daily Living; Acute; Address; Affect; Affinity; Agriculture; Antibodies; Antigens; Area; Attention; Awareness; Biological; Biological Assay; Blood; Canis familiaris; Carrier Proteins; Cattle; Centers for Disease Control and Prevention (U.S.); Characteristics; Clinical; Clinical Microbiology; Clinical Research; Collaborations; Collection; Communities; Country; Culture Techniques; Databases; Deposition; Detection; Development; Diagnosis; Diagnostic; Diagnostic Procedure; Diagnostic tests; Disease; Early Diagnosis; Emerging Communicable Diseases; Environment; Environmental Exposure; Enzyme-Linked Immunosorbent Assay; Epidemic; Epidemiology; Family member; Family suidae; Frequencies; Future; Genbank; Gene Family; Generations; Genome; Genomics; Geographic Locations; Geography; Goals; Gold; Hospitals; Human; I-antigen; Infection; Integration Host Factors; International; Knowledge; Laboratories; Leptospira; Leptospirosis; Letters; Lipopolysaccharides; Marsupialia; Medical; Medicine; Methods; Microarray Analysis; Molecular; Monoclonal Antibodies; Occupational; Occupations; Outcome; Outpatients; Pathogenicity; Patients; Performance; Peru; Peruvian; Prevention education; Protein Microchips; Proteins; Public Health; Publishing; Research; Risk; Risk Factors; Rodent; Rural; Sampling; Science; Sensitivity and Specificity; Serologic tests; Serum; Severities; Site; Source; Specimen; Sri Lanka; T-Lymphocyte; Techniques; Testing; Thinking; Time; Translational Research; Translations; Urine; Virulence; Water Buffalo; Work; World Health Organization; Zoonoses; base; burden of illness; clinically actionable; clinically relevant; direct application; disorder prevention; experimental study; field study; follow-up; improved; novel; novel diagnostics; novel strategies; pathogen; programs; prospective; 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）：拟议的U19 ICIDR项目侧重于钩端螺旋体的人类感染和疾病。我们的总体方针是利用基本的生物科学方法，结合秘鲁和斯里兰卡流行病学背景下的临床/实地研究，开发新的、临床可行的诊断测试。考虑到钩端螺旋体在地方、区域和国际上的多样性，拟议的研究解决了该领域迄今无法克服的差距，即获得廉价、敏感和高效的钩端螺旋体病诊断检测，但无论潜在的传播动态如何，都易于部署和有效。这些检测的准确性和效率的提高将使适当治疗的及时实施成为可能，这对改善临床结果至关重要。该规划的总体目标是开发强大的工具和方法，有效量化全球钩端螺旋体病负担，解决世界卫生组织钩端螺旋体病流行病学参考小组（LERG）阐明的国际钩端螺旋体病研究界共同的几个关键目标。1,2这些方法适用于所有钩端螺旋体病流行和容易流行的地点，总结如下：