Genetic Variation and Evolution of Artemisinin Resistance

青蒿素耐药性的遗传变异和进化

• 批准号: 8649014
• 负责人: Daniel L HARTL
• 金额: $ 68.32万
• 依托单位: HARVARD SCHOOL OF PUBLIC HEALTH
• 依托单位国家: 美国
• 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/8649014
• 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

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）： 青蒿素抗性的遗传变异和进化疟疾是世界上最大的杀手之一。《2010年世界疟疾报告》估计，每年有近2.25亿人患上急性疟疾，约100万人将死于疟疾。在缺乏有效疟疾疫苗的情况下，化疗仍然是治疗和预防该疾病的主要手段。恶性疟原虫是最危险的疟疾类型，其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。对抗叶酸剂和氯喹等抗疟药物的抗药性已从亚洲蔓延到整个非洲，对二线和三线药物的抗药性现已司空见惯。“青蒿素耐药性的遗传变异和进化”项目将利用群体遗传学和基因组学的工具，通过确认青蒿素耐药性表型、鉴定青蒿素耐药性相关基因和验证青蒿素耐药性相关候选基因，扩大我们对疟疾遗传变异和疟原虫微生物耐药性的基本认识。由于抗药性的出现有可能超过有效的新抗疟药物的开发速度，因此建立新抗药性预警系统是战胜疟疾的一个重要组成部分。