Surveillance to track and characterize antimalarial resistance trends in Ugandan Plasmodium falciparum parasites (STARTUP)

监测追踪和表征乌干达恶性疟原虫寄生虫的抗疟药耐药性趋势（STARTUP）

• 批准号: 10567404
• 负责人: Melissa D Conrad
• 金额: $ 78.91万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-12-20 至 2027-11-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10567404
• 关键词: Address; Africa; Age; Anti-malarial drug resistance; Antimalarials; Artemisinins; Automobile Driving; Biological Assay; Blood; CRISPR/Cas technology; Cessation of life; Clinical; Collection; Combined Modality Therapy; Communication; Country; Detection; Drug Exposure; Drug resistance; Epidemiologic Factors; Epidemiology; Evolution; Fright; Genetic; Genetic Polymorphism; Genotype; Geography; Goals; Growth; Hot Spot; Household; Immunity; In Vitro; Incidence; Individual; Infection; Infrastructure; Intervention; Laboratories; Malaria; Maps; Mediating; Metadata; Modernization; Molecular; Molecular Epidemiology; Mutation; Parasite resistance; Parasites; Parasitology; Pharmaceutical Preparations; Phenotype; Plasmodium falciparum; Policies; Policy Maker; Population; Population Genetics; Positioning Attribute; Predisposition; Prevalence; Public Health; Reporting; Research Activity; Resistance; Resolution; Rwanda; Site; Testing; Time; Uganda; Urbanicity; Validation; candidate validation; deep sequencing; fitness; improved; molecular marker; novel; novel therapeutics; response; transmission process; trend

PROJECT SUMMARY/ABSTRACT: New studies in Uganda and Rwanda have reported increasing prevalence of mutations in pfkelch13 (K13) associated with delayed parasite clearance following clinical or in vitro treatment with artemisinins, suggesting that fears that resistance of Plasmodium falciparum to artemisinins will emerge in Africa, where >90% of malaria cases and deaths occur, have been realized. However, the extent of resistance to components of artemisinin-based combination therapies (ACTs) is not well understood. Our ongoing research activities and well-established infrastructure in Uganda put us in a unique position to rapidly address urgent needs for improved surveillance and characterization of resistance to artemisinins and partner drugs in Uganda. Benefitting from a network of 80 surveillance sites across the country and modern laboratories in Kampala and Tororo, we will use molecular, parasitological and epidemiological approaches a) to evaluate the origins, prevalence and distribution of known markers of artemisinin and ACT partner drug resistance and to characterize the genetic background(s) that facilitate the establishment and spread of resistance phenotypes, b) assess associations between genotypes and drug susceptibility/fitness phenotypes, and c) assess ecological and epidemiological factors that facilitate the evolution of resistance. With resistance to important drugs still geographically focal, our goal is to identify key drivers of its emergence and spread, and then to promptly inform public health leaders on the best means of blunting the spread of resistance across Africa.

项目概要/摘要： 乌干达和卢旺达的新研究报告 pfkelch13 (K13) 突变的患病率不断增加 与青蒿素临床或体外治疗后寄生虫清除延迟有关，表明 担心非洲会出现恶性疟原虫对青蒿素的耐药性，该地区超过 90% 的疟原虫 疟疾病例和死亡的发生，已经成为现实。然而，对组件的抵抗程度 基于青蒿素的联合疗法（ACT）尚不清楚。我们正在进行的研究活动和 乌干达完善的基础设施使我们处于独特的地位，可以迅速满足紧急需求 改善乌干达青蒿素及其伙伴药物耐药性的监测和特征描述。 受益于由全国 80 个监测点组成的网络以及坎帕拉和坎帕拉的现代化实验室 托罗罗，我们将使用分子、寄生虫学和流行病学方法 a) 来评估起源， 青蒿素和 ACT 伙伴耐药性已知标志物的流行率和分布 描述促进抗性表型建立和传播的遗传背景， b) 评估基因型和药物敏感性/适应性表型之间的关联，以及 c) 评估 促进耐药性进化的生态和流行病学因素。具有重要的抵抗力 毒品在地理上仍然是焦点，我们的目标是确定其出现和传播的关键驱动因素，然后 及时向公共卫生领导人通报遏制耐药性在非洲蔓延的最佳方法。