Molecular epidemiology of drug resistance and population genetic structure of Pla

Pla耐药分子流行病学及群体遗传结构

• 批准号: 8333855
• 负责人: Fangli Lu
• 金额: $ 5.03万
• 依托单位: SUN YAT-SEN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8333855
• 关键词: Africa; Antimalarials; Attention; Biochemistry; Cessation of life; Characteristics; China; Chloroquine; Chloroquine resistance; Country; Data; Development; Dihydrofolate Reductase; Dihydropteroate Synthase; Drug resistance; Economic Development; Epidemiology; Evolution; Folic Acid Antagonists; Genes; Genetic Markers; Genetic Polymorphism; Genetic Population Study; Genetic Variation; Genotype; Geographic Distribution; Goals; Haplotypes; Health Benefit; Human; In Vitro; Individual; Infection; Intervention; Island; Lead; Life; Longevity; Malaria; Measures; Methods; Microsatellite Repeats; Molecular; Molecular Epidemiology; Monitor; Morbidity - disease rate; Morphology; Mutation; Parasites; Patients; Pattern; Pharmaceutical Preparations; Phenotype; Plasmodium falciparum; Point Mutation; Policies; Population; Prevalence; Province; Public Health; Pyrimethamine; Pyrimethamine-Sulfadoxine; Relapse; Reporting; Research; Resistance; Risk; Single Nucleotide Polymorphism; Southeastern Asia; Structure; Sulfadoxine; Sulfadoxine-pyrimethamine resistance; Suspension substance; Suspensions; Variant; Vivax Malaria; abstracting; base; combat; disorder control; geographic population; in vivo; population genetic structure; programs; public health priorities; resistance mutation; resistant strain; transmission process

Project Summary/Abstract Malaria remains a serious public health problem in China. In the subtropical Yunnan Province and the tropical Hainan Island of China, malaria has been the most endemic with high transmission of both Plasmodium falciparum and P. vivax. However, most of the attention in terms of research and interventions have been focused in Africa and Southeast Asia, very few studies of malaria in China have been conducted. Because of extensive use, chloroquine (CQ) has now lost its efficacy due to the emergence of resistant strains in most parts of the world. Meanwhile, suspension of the use of CQ has resulted in reappearance of CQ sensitivity. However, there were differences in the evolution of CQ resistance between parasites from Yunnan and Hainan, the exact mechanism needs to be investigated. Sulfadoxine-pyrimethamine (SP) targets the dhfr and dhps genes of P. falciparum, and point mutations that confer resistance have been widely reported worldwide. Documenting the identity and extent of SP resistance is also critical for policy decisions regarding antimalarial drugs. In addition, P. vivax causes a large burden of morbidity in the world including China but traditionally has been understudied. Based on these, our long-term goal of this proposal is 1) to identify single-nucleotide polymorphism (SNP) and characterize the geographic distribution of genetic diversity, population structure, and haplotype variability at drug resistant loci of P. falciparum from Yunnan and Hainan, China, 2) to examine the geographic population structure, levels of genetic diversity of P. vivax using microsatellite and SNP, and 3) to yield valuable information for making more effective malaria control policies in China. In the past several years we have developed the molecular methods to study the genetics, population diversity, and evolution of malaria parasites, and have done some preliminary studies on malaria field isolates from Yunnan and Hainan using genetic markers, thus enabling us to study the molecular epidemiology of these important malaria parasites in this proposal. The specific aims are to: 1. Determine genetic polymorphisms associated with CQ resistance (CQR) in P. falciparum field isolates from Yunnan and Hainan provinces, China. 2. Determine the point mutation prevalence in the dhfr (pyrimethamine drug resistance) and dhps (sulfadoxine drug resistance) genes associated with SP resistance in P. falciparum field isolates from Yunnan and Hainan provinces, China. 3. Assess the changes of P. vivax genotypes using pvcsp, pvmsp1, pvmsp3-¿ genes, and microsatellite markers and determine the geographic structure and specific epidemiological characteristics of P. vivax transmission in Yunnan and Hainan, China. 1

项目摘要/摘要 在中国，疟疾仍然是一个严重的公共卫生问题。在亚热带中 云南省和热带海南中国岛，疟疾是最多的 内细胞和疟原虫的高传播和疟原虫的传播。然而， 在研究和干预措施方面的大多数关注都集中在 非洲和东南亚，在中国很少有关于疟疾的研究。 由于广泛使用，氯喹（CQ）现在由于 世界大部分地区的抗性菌株出现。平均暂停 CQ的使用导致CQ灵敏度的重新出现。但是，有 云南寄生虫与寄生虫之间CQ抗性演变的差异 海南，需要研究确切的机制。亚磺氧胺 - 甲胺 （sp）针对恶性疟原虫的DHFR和DHP基因，并点突变。 阻力已在全球范围内广泛报道。记录身份和范围 SP抗性对于有关抗疟药的政策决策也至关重要。在 此外，维瓦克斯（P. vivax）在包括中国在内的世界上引起了大量发病率 传统上已经被理解了。基于这些，我们的长期目标 建议是1）识别单核苷酸多态性（SNP）并表征 遗传多样性，种群结构和单倍型的地理分布 来自中国云南和海南的恶性疟原虫的耐药性位置的可变性，2） 检查地理种群结构，植物假单胞菌的遗传多样性水平 使用微卫星和SNP，以及3）产生有价值的信息，以制作更多 中国有效控制政策。在过去的几年中 研究遗传学，种群多样性和进化的分子方法 疟疾寄生虫，并且已经对疟疾田间分离株进行了一些初步研究 从Yunnan和Hainan使用遗传标记，从而使我们能够研究 在本提案中，这些重要的疟疾寄生虫的分子流行病学。 具体目的是： 1。确定与C中的CQ抗性（CQR）相关的遗传多态性。 来自中国云南和海南计划的恶意田地分离。 2。确定DHFR（嘧啶药）中的点突变患病率 抗性）和DHP（磺胺毒素耐药性）基因 来自中国云南和海南计划的恶性疟原虫田间菌株的抵抗。 3。使用PVCSP，PVMSP1，PVMSP3-€评估疟原虫基因型的变化。 基因和微卫星标记，并确定地理结构和 云南和海南氏疟原虫传播的特定流行病学特征， 中国。 1