Development of an ELISA for serosurveillance of human hookworm

钩虫感染，由美洲钩虫、十二指肠钩口线虫和锡兰钩口线虫引起 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 南美洲的部分地区。最近的研究显示，这种寄生虫在美国重新出现。负担 钩虫感染的可能性通常与慢性病有关，而不是与宿主的死亡率有关。贫血, 发育迟缓以及智力和认知缺陷是 儿童和育龄妇女持续感染钩虫。此外，慢性低强度 钩虫感染降低了疫苗的效力，并加剧了其他全球相关的传染病，如 如结核病、疟疾和艾滋病毒，它们与钩虫共同流行。当前控制钩虫的策略 主要依靠大众药监局的驱虫药。然而，最近的证据表明 质疑这种方法在控制和消灭流行人群中钩虫的长期有效性， 这引发了人们对出现抗药性的担忧。目前筛查STH感染的方法是 粪便中鸡蛋的显微镜显示和定量。对于筛查，世卫组织认为加藤卡茨 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低。 处理每个样本的多个涂片或在连续几天内检查多个样本可以增加 加藤-卡茨厚涂片的敏感性。虽然筛选多个样本可以提高灵敏度，但它提出了 这是相当大的后勤和财政挑战，并不是在所有情况下都是可行的。为了解决这个问题，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查工具 要求，目前还不能满足加藤-卡茨的厚抹黑。为了满足这一需要，在第一阶段，我们建议 钩虫感染人免疫球蛋白酶联免疫吸附试验的建立与耶鲁大学合作 ，我们将进行体内和体外研究相结合，以帮助表征生物标记物 兴趣(目标1)，将用于开发酶联免疫吸附试验(目标2)。然后我们将评估化验结果 绩效(目标2)使用具有良好特征的血清样本队列。我们的目标是实现敏感度和 TPP中概述的特异性，并在第二阶段进一步改进。拟议的商业ELISA试剂盒将 允许取代现有的、相对不敏感的显微镜工具，作为监测的一部分 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。

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.