Polymorphism in pfcrt and pfmdr1 genes of malaria parasite populations in South-East countries

东南部国家疟原虫种群 pfcrt 和 pfmdr1 基因多态性

基本信息

批准号：
14406003
负责人：
UEMURA Haruki
金额：
$ 4.22万
依托单位：
Nagasaki University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2004
项目状态：
已结题

项目摘要

The emergence and spread of drug resistant malaria parasite Plasmodium falciparum has been a major obstacle to control and management of malaria. We have analyzed genetic polymorphism of pfcrt and pfmdr1 genes of P. falciparum, obtained from South-East Asis counties, Vietnam, Myanmar and Indonesia. There found specific characteristics in polymorphism of genotypes of the field isolates in each country. Many of the pfcrt genes from Vietnam samples exhibited a chloroquine sensitive genotype and the ratio of the sensitive type is more increasing in recent years. On the other hand, all of the pfcrt genes from Indonesia contained Thr76, which is essential for chloroquine resistant. Samples from these two countries are very interesting regarding to the effect of chloroquine; chloroquine is not used for treatment of P falciparum for several years in Vietnam and chloroquine is still the first choice of treatment in Indonesia. There are many types of pfcrt and pfmdr1 genes in Myanmar isolates, where patients are able to obtain several different drugs for treatment. The genotype analysis indicated that parasites have been essentially selected by drugs used in each region, and the polymorphic difference in parasites of each country might be the accumulated drug effects on parasites in each patient and the effects would be appeared as a ratio of genotypes.The identification protocols of four human malaria parasites by PCR have been established. However, some unstable results were obtained in P malarie and P ovale from Vietnam samples. We have set up a modified primer sets and shown the usefulness of the improved methods.

恶性疟原虫的抗药性疟疾疟原虫的出现和传播一直是控制和管理疟疾的主要障碍。我们已经分析了从东南ASIS县，越南，缅甸和印度尼西亚获得的恶性疟原虫PFCRT和PFMDR1基因的遗传多态性。在那里发现了每个国家的田间分离株的多态性特征。来自越南样品的许多PFCRT基因表现出氯喹敏感基因型，而敏感类型的比率在近年来增加。另一方面，来自印度尼西亚的所有PFCRT基因都包含THR76，这对于耐氯喹至关重要。这两个国家的样本对氯喹的影响非常有趣。氯喹在越南几年内不用于治疗p恶性，氯喹仍然是印度尼西亚治疗的首选。缅甸分离株中有许多类型的PFCRT和PFMDR1基因，患者能够获得几种不同的药物进行治疗。基因型分析表明，寄生虫基本上是由每个区域中使用的药物选择的，每个国家的寄生虫的多态性差异可能是每位患者中对寄生虫的累积影响，并且该作用将作为基因型的比率。已经建立了PCR的四种人类疟疾寄生虫的识别方案。但是，从越南样品中获得了P Malarie和P Ovale的一些不稳定结果。我们已经设置了一个修改的底漆集，并显示了改进方法的有用性。