Molecular epidemiology of drug resistance and population genetic structure of Pla

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 云南省和热带海南岛的中国，一直是疟疾最多的地区 恶性疟原虫和间日疟原虫高度传播的地方性疾病。然而， 在研究和干预方面的大部分注意力都集中在 在非洲和东南亚，中国对疟疾的研究很少。 由于氯喹(CQ)的广泛使用，现已因 在世界大部分地区出现了耐药菌株。同时，暂停 CQ的使用导致了CQ敏感性的重现。然而，有一些 云南和云南寄生虫对CQ抗性进化的差异 在海南，其确切的作用机制还有待研究。磺胺多辛-乙胺嘧啶 (SP)针对恶性疟原虫的dhfr和dhps基因，以及与之相关的点突变 耐药性在世界范围内得到了广泛的报道。记录身份和范围 对SP耐药性的了解对有关抗疟疾药物的政策决策也至关重要。在……里面 此外，间日疟原虫在世界上造成了很大的发病率负担，包括中国在内，但 传统上，人们对此研究不足。在此基础上，我们的长期目标是 建议是1)识别单核苷酸多态(SNP)并表征 遗传多样性、种群结构和单倍型的地理分布 云南、海南恶性疟原虫耐药基因座变异中国，2) 研究间日疟原虫地理种群结构、遗传多样性水平 利用微卫星和SNP，以及3)提供有价值的信息，以制造更多 中国有效的疟疾控制政策。在过去的几年里，我们发展了 用分子方法研究白纹伊蚊的遗传学、种群多样性和进化 疟疾寄生虫，并对疟疾现场分离株进行了一些初步研究 利用遗传标记，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在本提案中。这个 具体目标是： 1.确定与赤霉病抗性(CQR)相关的遗传多态性。 云南和海南两省的恶性疟原虫田间分离株中国。 2.确定DHFR(乙胺嘧啶类药物)中点突变的发生率 耐药)和磺胺多辛耐药(DHPS)基因与SP相关 云南、海南恶性疟原虫田间分离株抗药性研究，中国。 3.用pvcsp、pvmsp1、pvmsp3-？评估间日疟原虫基因分型的变化 基因和微卫星标记，并决定地理结构和 云南、海南间日疟原虫传播的特殊流行病学特征， 中国。 1

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