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: 8497661
• 负责人: Fangli Lu
• 金额: $ 4.77万
• 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 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8497661
• 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

项目总结/摘要 疟疾在中国仍然是一个严重的公共卫生问题。亚热带 云南省和热带的中国海南岛，疟疾一直是最多的 恶性疟原虫和间日疟原虫的高度传播。然而，在这方面， 在研究和干预方面，大部分注意力都集中在 非洲和东南亚，中国对疟疾的研究很少。 由于广泛使用，氯喹（CQ）现已因其毒性而失去功效 在世界大部分地区出现耐药菌株。与此同时， CQ的使用导致CQ敏感性的再现。但有 云南省寄生虫对氯喹抗性的进化差异 海南，确切的机制需要调查。效磺胺 (SP)靶向恶性疟原虫的dhfr和dhps基因， 耐药性已在世界范围内广泛报道。记录身份和范围 SP耐药性的评估对于有关抗疟药物的决策也至关重要。在 此外，间日疟原虫在包括中国在内的世界范围内造成了巨大的发病负担， 传统上被低估了。基于这些，我们的长期目标， 建议是1）鉴定单核苷酸多态性（SNP）并表征 遗传多样性、群体结构和单倍型的地理分布 中国云南和海南省恶性疟原虫耐药基因座的变异，2） 研究间日疟原虫的地理种群结构、遗传多样性水平 利用微卫星和SNP，3）产生有价值的信息， 中国有效的疟疾控制政策。在过去的几年里，我们开发了 研究遗传学、种群多样性和进化的分子方法 疟原虫，并对疟疾现场分离株进行了初步研究 从云南和海南使用遗传标记，从而使我们能够研究 这些重要的疟疾寄生虫的分子流行病学。的 具体目标是： 1.确定与CQ抗性（CQR）相关的遗传多态性。 云南和海南省的恶性疟原虫田间分离株。 2.确定DHFR（乙胺嘧啶药物）中的点突变率 与SP相关的dhps（磺胺类药物抗性）基因 中国云南省和海南省恶性疟原虫田间分离株的耐药性。 3.利用pvcsp、pvmsp 1、pvmsp 3 - 3基因型评估间日疟原虫基因型的变化 基因和微卫星标记，并确定地理结构， 云南和海南间日疟原虫传播的流行病学特征， 中国 1