Development of an ELISA for serosurveillance of human hookworm

钩虫感染，由美洲钩虫，钩口线虫和锡兰钩口线虫引起， 这是撒哈拉以南非洲、亚洲和非洲贫困社区营养不良和生长迟缓的主要原因， 南美洲的部分地区。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，智力和认知缺陷是最严重的后果之一， 儿童和育龄妇女的持续钩虫感染。此外，慢性低强度 钩虫感染降低了疫苗的效力并使其它全球相关的传染病恶化， 如肺结核、疟疾和艾滋病，这些疾病与钩虫共同流行。当前控制钩虫的策略 主要依靠大众药物管理局的驱虫药。然而，最近的证据表明， 质疑这种方法在控制和消除地方性人群中钩虫病方面的长期有效性， 引起了人们对抗药性出现的担忧。目前筛查STH感染的方法是 粪便中虫卵的显微镜显示和定量。对于筛查，世卫组织认为Kato-Katz 厚涂片作为诊断钩虫感染的基准。然而，这种方法的灵敏度很差。 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厚涂片的灵敏度。虽然筛选多个样本提高了灵敏度，但它提出了 在后勤和财政方面面临相当大的挑战，并不是在所有情况下都切实可行。为此，世卫组织最近 发布了土传蠕虫的目标产品简介，以开发符合以下要求的低成本筛选工具： 要求，目前没有满足加藤-卡茨厚抹黑。为了满足这一需求，在第一阶段，我们建议 开发ELISA以筛选抗钩虫感染的人IgG。与耶鲁大学合作 大学，我们将进行计算机和体外研究的组合，以帮助表征生物标志物的 目标1），其将用于ELISA的开发（目标2）。然后，我们将评估分析 使用良好表征的血清样品队列进行性能（目的2）。我们的目标是实现敏感性和 TPP中概述的特异性，在第二阶段进一步改进。拟议的商业ELISA试剂盒将 允许替换现有的、相对不敏感的显微镜工具，以集成为监测的一部分。 以及世界各地钩虫感染的评估项目。这将直接影响未来的全球政策 和控制钩虫感染的策略。

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.