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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.

耐药性疟原虫恶性疟原虫的出现和传播一直是疟疾控制和管理的主要障碍。我们分析了从东南亚各县、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。各国田间分离株基因型多态性均存在一定的特点。越南样本中许多pfcrt基因表现出对氯喹敏感的基因型，且近年来敏感型的比例不断增加。另一方面，来自印度尼西亚的所有 pfcrt 基因都含有 Thr76，这对于氯喹耐药至关重要。关于氯喹的作用，来自这两个国家的样本非常有趣；越南已有数年不再使用氯喹治疗恶性疟，而氯喹仍然是印度尼西亚的首选治疗方法。缅甸分离株中存在多种类型的 pfcrt 和 pfmdr1 基因，患者可以获得多种不同的药物进行治疗。基因型分析表明，疟原虫基本上是由各个地区所使用的药物选择的，而各个国家疟原虫的多态性差异可能是药物对每个患者体内寄生虫的累积效应，其效应会以基因型的比值的形式出现。建立了四种人类疟原虫的PCR鉴定方案。然而，在越南样品中的 P malarie 和 P ovale 中获得了一些不稳定的结果。我们建立了修改后的引物组并展示了改进方法的有用性。