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.

钩虫感染是由necator Americanus，Ancylostoma duodenale和Ancylostoma Ceylanicum引起的 撒哈拉以南非洲，亚洲和 南美部分地区。最近的研究揭示了该寄生虫在美国的重新出现。负担 钩虫感染通常与慢性疾病有关，而不是宿主中的死亡率。贫血， 发育不良的发展，智力和认知缺陷是最严重的结果之一 生殖年龄的儿童和妇女的持续性钩虫感染。另外，慢性低强度 钩虫感染可降低疫苗功效，并加剧其他全球相关的感染疾病 作为结核病，疟疾和艾滋病毒，与钩虫共同流行。当前控制钩虫的策略 主要依靠大规模药物管理驱虫药物。但是，最近的证据呼吁 质疑这种方法控制和消除流行人群中的钩虫的长期有效性， 引起人们对耐药性出现的关注。当前筛查STH感染的方法是 粪便中卵的微观演示和定量。为了筛选，考虑了加藤 - 卡茨 厚厚的涂片作为诊断钩虫感染的基准。但是，这种方法的敏感性差。 每个样品处理多个涂片或连续检查多个样品可以增加 Kato-Katz厚涂片的灵敏度。在筛选多个样品提高灵敏度时，它表示 巨大的后勤和财务挑战，在所有情况下都不是实际的。解决这个问题，最近 发布了针对土壤传播的舵机的目标产品概况，以开发低成本筛查工具来满足 需求，目前尚未满足Kato-Katz厚涂片。为了满足这一需求，在第一阶段，我们提出了 开发ELISA以筛选人类IgG针对钩虫感染。与耶鲁大学合作 大学，我们将共同执行silico和维特罗研究的结合，以帮助表征生物标志物 兴趣（AIM 1），将用于开发ELISA（AIM 2）。然后我们将评估测定 性能（AIM 2）使用良好的血清样品群体。我们的目标是实现灵敏度和 TPP中概述的特异性，II阶段进一步改善。拟议的商业Elisa套件将 允许更换现有的，相对不敏感的微观工具，以作为监视的一部分集成 以及全球钩虫感染的评估计划。这将直接影响未来的全球政策 和控制钩虫感染的策略。