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.

钩虫感染是由美洲钩虫、十二指肠钩虫和蓝球钩虫引起的