Genetic Variation and Evolution of Artemisinin Resistance

青蒿素耐药性的遗传变异和进化

基本信息

批准号：
8439482
负责人：
Daniel L HARTL
金额：
$ 65.7万
依托单位：
HARVARD SCHOOL OF PUBLIC HEALTH
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-04-05 至 2017-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8439482
关键词：
Africa African Anti-malarial drug resistance Antimalarials Artemisinins Asia Beds Biological Biological Assay Candidate Disease Gene Cessation of life Child Chloroquine Chloroquine resistance Clinical Combined Modality Therapy Development Disease Drug Combinations Drug Exposure Drug resistance Drug usage Early Diagnosis Effectiveness Exhibits Failure Falciparum Malaria Fever Folic Acid Antagonists Gene Frequency Genes Genetic Genetic Variation Genome Genomics Geographic Locations Health Benefit In Vitro Infection Inhibitory Concentration 50 Insecticides Laboratories Location Malaria Malaria Vaccines Malaria prevention Measures Microbial Drug Resistance Modeling Molecular Monitor Mosquito Control Parasites Patients Pharmaceutical Preparations Phenotype Population Population Genetics Public Health Relative (related person)Reporting Resistance Sampling Senegal Signal Transduction Site Southeastern Asia Staging System Tail Time Transfection World Health Organization artemisinine artesunate base chemotherapy disorder control disorder prevention drug development drug testing effectiveness clinical trial follow-up gene discovery genetic evolution genetic variant pressure public health relevance resistance allele resistance mechanism response success tool transmission process

项目摘要

DESCRIPTION (provided by applicant): Genetic Variation and Evolution of Artemisinin Resistance Malaria is one of the biggest killers in the world. The 2010 World Malaria Report estimates that almost 225 million people each year become acutely ill from the disease-and approximately one million will die from malaria. In the absence of an effective malaria vaccine, chemotherapy remains the mainstay for treatment and prevention of the disease. Genetic variability of the most dangerous type of malaria, Plasmodium falciparum, underlies its transmission success and impedes efforts to control disease. Drug resistance to antimalarial drugs such as antifolates and chloroquine has spread from Asia throughout Africa and resistance to second and third line drugs is now commonplace. Using the tools of population genetics and genomics, the "Genetic Variation and Evolution of Artemisinin Resistance" project will expand our fundamental understanding of both the genetic variation of malaria and microbial drug resistance among malaria parasites by confirming artemisinin resistance phenotypes, identify the gene (or genes) involved in artemisinin drug resistance, and validate the candidate gene (or genes) involved in artemisinin resistance. Because the emergence of drug resistance threatens to outpace the development of effective new antimalarial drugs, the development of an early warning system for emerging resistance is an essential component to defeating malaria.

描述（由申请人提供）：青蒿素抗性疟疾的遗传变异和进化是世界上最大的杀手之一。 2010年世界疟疾报告估计，每年将近2.25亿人因这种疾病而严重患病，大约一百万将死于疟疾。在没有有效的疟疾疫苗的情况下，化学疗法仍然是治疗和预防该疾病的主要支柱。最危险的疟疾类型，恶性疟原虫的遗传变异性是其传播成功的基础，并阻碍了控制疾病的努力。抗疟疾药物（如抗焦酸盐和氯喹）的耐药性已从亚洲传播到整个非洲，对第二和第三行药物的抵抗力现在很普遍。使用人群遗传学和基因组学的工具，“抗疟疾的遗传变异和进化”项目将扩展我们对疟疾遗传变异和疟原虫抗微生物耐药性的基本理解，通过证实涉及遗传性的抗遗传学（或基因），并鉴定糖尿病（或对基因），并识别糖尿病（或对基因），并识别糖尿病（或对基因），并识别（或鉴定）（概念）（或者）青蒿素耐药性。由于耐药性的出现有可能超过有效的新抗疟药的发展，因此开发出一种新兴抗药性的预警系统是击败疟疾的重要组成部分。