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Rigorous Assessment of P. vivax Relapses and Primaquine Efficacy for Radical Cure

严格评估间日疟原虫复发和伯氨喹根治疗效

基本信息

批准号：
10219069
负责人：
David Serre
金额：
$ 63.96万
依托单位：
UNIVERSITY OF MARYLAND BALTIMORE
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-07-17 至 2025-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10219069
关键词：
Address Adherence Africa Alleles Area Biology Blood Blood specimen CYP2D6 gene Cambodia Chloroguanide Collaborations Collection Country Detection Development Dose Drug Kinetics Enrollment Erythropoiesis Falciparum Malaria Fingers Frequencies G6PD gene Gene Expression Genes Genetic Polymorphism Genome Genomic approach Genomics Genotype Human In Vitro Incidence Individual Infection Inflammation Laboratories Liver Malaria Metabolism Modernization Morbidity - disease rate Parasites Patients Pattern Pharmaceutical Preparations Plasmodium falciparum Plasmodium vivax Population Predisposition Primaquine Primary Infection Proteins Proxy Recrudescences Regimen Relapse Retreatment Sepsis Serology Sporozoites Testing Time Variant Vivax Malaria Work atovaquone clinically relevant design efficacy evaluation field study genome sequencing improved insight patient subsets response side effect transmission process whole genome

项目摘要

Plasmodium vivax threatens half of the world’s population. While on-going malaria elimination efforts are successfully reducing the burden of falciparum malaria worldwide, the situation is much less promising for P. vivax. In particular, the unique ability of P. vivax parasites to remain dormant in the liver and cause relapse infections weeks or months later greatly complicates malaria elimination campaigns. Here we propose to conduct a tightly-controlled field study in Cambodia, specifically designed to support and empower state-of-the-art genomic analyses, to determine the frequency of relapse and the factors associated with hypnozoite reactivation, as well as to rigorously evaluate the efficacy of different doses of primaquine for radical cure treatment. Our studies will provide a unique perspective on P. vivax relapse and will contribute to better understand how to successfully eliminate this understudied parasite.

间日疟原虫威胁着世界上一半的人口。虽然正在进行的消灭疟疾的努力是虽然成功地减少了全球恶性疟疾的负担，但P. 间日疟原虫特别是间日疟原虫在肝脏中保持休眠并导致复发的独特能力感染数周或数月后，疟疾消除运动变得非常复杂。在这里，我们建议进行在柬埔寨进行严格控制的实地研究，专门用于支持和授权最先进的基因组分析，以确定复发的频率和与催眠子再激活相关的因素，以及严格评估不同剂量伯氨喹用于根治治疗的功效。我们研究将为间日疟原虫复发提供一个独特的视角，并将有助于更好地了解如何成功地消灭了这种未被充分研究的寄生虫