Development of an ELISA for serosurveillance of human hookworm

开发用于人类钩虫血清监测的 ELISA

• 批准号: 10697222
• 负责人: Andrew E. Levin
• 金额: $ 30万
• 依托单位: KEPHERA DIAGNOSTICS, LLC
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10697222
• 关键词: Address; Africa South of the Sahara; Age; Ancylostoma (genus); Anemia; Anthelmintics; Antibodies; Antigens; Area; Asia; Benchmarking; Biological Assay; Biological Markers; Biology; Child; Chronic; Chronic Disease; Cognitive; Collaborations; Communicable Diseases; Country; Detection; Development; Diagnosis; Diagnostic; Drug resistance; Effectiveness; Enzyme-Linked Immunosorbent Assay; Exposure to; Feces; Filarial Elephantiases; Friends; Future; Goals; Growth; HIV; Hamsters; Helminths; Hemorrhage; Hookworm Infections; Hookworms; Human; IgE; Immunoglobulin G; Immunoprecipitation; In Vitro; Incidence; Individual; Infection; Iron deficiency anemia; Laboratories; Letters; Liquid Chromatography; Malaria; Malnutrition; Methods; Microscopic; Microscopy; Molecular; Monitor; Morbidity - disease rate; Necator americanus; Old World Hookworm; Onchocerciasis; Outcome; Parasites; Parasitic Diseases; Peptides; Performance; Pharmaceutical Preparations; Phase; Policies; Population; Positioning Attribute; Poverty Areas; Predisposition; Pregnant Women; Prevalence; Program Evaluation; Proteins; Proteomics; Publishing; Reagent; Recombinant Proteins; Recommendation; Research; Research Personnel; Resistance; Resources; Sampling; Screening procedure; Sensitivity and Specificity; Serum; Small Intestines; Soil; South America; Specificity; Standardization; Testing; Thick; Tuberculosis; Universities; Woman; Work; World Health Organization; assay development; benzimidazole; candidate marker; cohort; cost; egg; hatching; high risk population; human model; immunoreactivity; improved; in silico; interest; manufacture; manufacturing scale-up; mortality; neglected tropical diseases; novel; poor communities; programs; prototype; reproductive; screening; screening panel; serosurveillance; stoichiometry; synthetic peptide; tandem mass spectrometry; tool; transmission process; vaccine efficacy

Hookworm infection, caused by Necator americanus, Ancylostoma duodenale, and Ancylostoma ceylanicum is a leading cause of malnutrition and stunted growth in poor communities across sub-Saharan Africa, Asia, and parts of South America. Recent studies have revealed the re-emergence of this parasite in the USA. The burden of hookworm infection is generally associated with chronic illness rather than mortality in the host. Anemia, stunted development, and intellectual and cognitive deficiencies are among the most serious outcomes of persistent hookworm infections in children and women of reproductive age. In addition, chronic low-intensity hookworm infection reduces vaccine efficacy and exacerbates other globally relevant infectious diseases such as tuberculosis, malaria, and HIV, which are co-endemic with hookworm. Current strategies to control hookworm rely primarily on the Mass Drug Administration of anthelminthic drugs. However, recent evidence calls into question the long-term effectiveness of this approach to control and eliminate hookworm in endemic populations, raising concern about the emergence of drug resistance. The current method to screen for STH infections is microscopic demonstration and quantification of eggs in the stool. For screening, WHO considers the Kato-Katz thick smear as a benchmark for diagnosing hookworm infection. This method, however, has poor sensitivity. Processing multiple smears per sample or examining multiple samples over consecutive days can increase the sensitivity of the Kato-Katz thick smear. While screening multiple samples improves sensitivity, it presents considerable logistical and financial challenges and is not practical in all settings. To address this, WHO recently published a Target Product Profile for soil-transmitted helminths to develop low-cost screening tools that meet demands, currently not met by the Kato-Katz thick smear. To address this need, in Phase I we propose the development of an ELISA to screen for human IgG against hookworm infection. In collaboration with Yale University, we will perform a combination of in-silico and in-vitro studies, to help characterize biomarkers of interest (Aim 1), which will be used in the development of an ELISA (Aim 2). We will then evaluate assay performance (Aim 2) using well-characterized cohorts of serum samples. Our goal is to achieve sensitivity and specificity as outlined in the TPP, with further improvement in Phase II. The proposed commercial ELISA kit will allow for the replacement of the existing, relatively insensitive microscopic tools, to integrate as part of monitoring and evaluation programs for hookworm infection around the world. This will directly impact future global policy and strategy for the control of hookworm infection.

钩虫感染，由美洲钩虫、十二指肠钩虫和锡兰钩虫引起 是撒哈拉以南非洲、亚洲和非洲贫困社区营养不良和生长迟缓的主要原因 南美洲部分地区。最近的研究表明这种寄生虫在美国重新出现。负担 钩虫感染通常与宿主的慢性疾病有关，而不是死亡。贫血， 发育迟缓以及智力和认知缺陷是最严重的后果之一 儿童和育龄妇女持续感染钩虫。此外，长期低强度 钩虫感染会降低疫苗功效并加剧其他全球相关传染病，例如 如结核病、疟疾和艾滋病毒，它们与钩虫共同流行。目前控制钩虫的策略 主要依靠大众药品管理局的驱虫药。然而，最近的证据表明 质疑这种方法在流行人群中控制和消除钩虫的长期有效性， 引起人们对耐药性出现的担忧。目前筛查 STH 感染的方法是 粪便中虫卵的显微镜观察和定量。对于筛查，世卫组织考虑采用 Kato-Katz 厚涂片作为诊断钩虫感染的基准。然而，该方法的灵敏度较差。 处理每个样本的多个涂片或连续几天检查多个样本可以增加 Kato-Katz 厚涂片的敏感性。虽然筛选多个样本可以提高灵敏度，但它呈现 相当大的后勤和财务挑战，并且并非在所有情况下都可行。为了解决这个问题，世界卫生组织最近 发布了土源性蠕虫目标产品简介，以开发满足以下要求的低成本筛查工具 目前，Kato-Katz 厚涂片无法满足要求。为了满足这一需求，在第一阶段，我们建议 开发 ELISA 来筛选抗钩虫感染的人类 IgG。与耶鲁大学合作 在大学，我们将进行计算机模拟和体外研究的结合，以帮助表征生物标志物 兴趣（目标 1），将用于开发 ELISA（目标 2）。然后我们将评估检测 使用特征明确的血清样本组来评估性能（目标 2）。我们的目标是实现敏感性和 TPP 中概述的特异性，并在第二阶段得到进一步改进。拟议的商业 ELISA 试剂盒将 允许替换现有的、相对不敏感的微观工具，作为监测的一部分进行集成 以及世界各地钩虫感染的评估计划。这将直接影响未来的全球政策 以及控制钩虫感染的策略。