Digital serology for parallel parasitic disease detection

用于并行寄生虫病检测的数字血清学

• 批准号: 9255416
• 负责人: Patrick S Daugherty
• 金额: $ 22.5万
• 依托单位: SERIMMUNE, INC.
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-01-01 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9255416
• 关键词: Acanthamoeba; Acute Disease; Address; Americas; Angiostrongylus cantonensis; Antibodies; Antibody Repertoire; Antibody Specificity; Antigen Targeting; Antigens; Archives; Autoimmune Diseases; Balamuthia mandrillaris; Bar Codes; Binding; Bioinformatics; Biological Assay; Blinded; Blood Cells; Blood Tests; Cardiac; Celiac Disease; Centers for Disease Control and Prevention (U.S.); Chagas Disease; Chronic; Chronic Disease; Clinical; Collection; Communicable Diseases; Computer software; Consensus; Custom; Data; Data Set; Databases; Detection; Diagnosis; Diagnostic; Diagnostic Sensitivity; Diagnostic Specificity; Diagnostic tests; Disease; Echinococcus granulosus; Entamoeba histolytica; Enzyme-Linked Immunosorbent Assay; Epitopes; Exhibits; Family; Gold; Heart Diseases; Human; Immunoassay; Individual; Infection; Knowledge; Laboratories; Lead; Leishmania; Measures; Methodology; Methods; Microscopic; Naegleria fowleri; Outcome; Parasites; Parasitic Diseases; Parasitic infection; Peptide Library; Peptides; Phase; Populations at Risk; Preparation; Process; Randomized; Reproducibility; Sampling; Sensitivity and Specificity; Serodiagnoses; Serologic tests; Serological; Specificity; Specimen; Taenia solium; Technology; Test Result; Testing; Time; Toxocara; Toxoplasma gondii; Trypanosoma cruzi; United States; Validation; accurate diagnosis; base; biomarker discovery; cost; diagnostic accuracy; diagnostic panel; digital; gastrointestinal; improved; molecular diagnostics; neglect; next generation sequencing; novel; pathogen; performance tests; prevent; specific biomarkers

The proposed project aims to build a diagnostic test for chronic T. cruzi infection and Chagas disease that not only improves testing performance but that can be readily integrated with similarly developed tests for most clinically important parasitoses. Current assays for Chagas disease, and other parasitic infections, lack desired levels of specificity, and require multiple independent assays and testing formats. Consequently, testing a single specimen for several different clinically important parasitic diseases becomes cost prohibitive and time consuming, delaying disease detection and treatment. We propose to address this problem by creating a single, all-in-one diagnostic test able to detect ten or more different clinically important parasitic diseases. Importantly, the proposed strategy could be expanded to a nearly arbitrary number of infectious diseases without resultant increases in final test cost. Towards a multiplexed parasitic disease test, we will first create an improved test for Chagas disease, that impacts about 350,000 individuals in the US, and 8 million in the Americas. To accomplish this, we will apply bacterial display peptide libraries, next-generation sequencing, and computational bioinformatics to identify a set of motifs and consensus peptides corresponding to antigenic peptide epitopes that when combined yield optimal sensitivity and specificity values in the discovery set. The motif and peptide panels will be validated using an independent specimen set. Assay reproducibility and stability will be measured. This project may thus lead to clinically useful tests to improve the rates of detection parasitic diseases their resultant complications.

该项目的目的是建立一个诊断测试慢性T。克氏锥虫病和南美锥虫病，这不仅提高了测试性能，但可以很容易地与类似开发的测试最临床上重要的寄生虫病。目前用于恰加斯病和其他寄生虫感染的测定缺乏期望水平的特异性，并且需要多个独立的测定和测试形式。因此，针对几种不同的临床上重要的寄生虫病测试单个样本变得成本高昂且耗时，从而延迟疾病检测和治疗。我们建议通过创建能够检测十种或更多种不同的临床重要寄生虫病的单一、多合一诊断测试来解决这个问题。重要的是，所提出的策略可以扩展到几乎任意数量的传染病，而不会导致最终测试成本的增加。 为了实现多重寄生虫病测试，我们将首先创建一种改进的查加斯病测试，该测试影响了美国约35万人，美洲约800万人。为了实现这一点，我们将应用细菌展示肽库，下一代测序和计算生物信息学来鉴定一组对应于抗原肽表位的基序和共有肽，当组合时，在发现集中产生最佳灵敏度和特异性值。将使用独立的标本集验证基序和肽组。将测量试验重现性和稳定性。因此，该项目可能导致临床上有用的测试，以提高寄生虫病及其并发症的检测率。