恶性疟原虫药物抗性已成为疟疾治疗和控制的重要障碍之一,而目前实施的药物抗性监控仅关注人体内疟原虫抗性变化,对于抗性经蚊媒传播遗传变化研究较少。前期研究发现鼠约氏疟原虫氯喹和甲氟喹抗性经蚊传后氯喹抗性增加,甲氟喹抗性丢失;而按蚊天然免疫可能对此发挥重要作用。因此本课题拟在前期研究基础上,首先利用PCR-RFLP分析疟疾流行现场的人和按蚊体内恶性疟原虫抗氯喹或磺胺相关基因(pfCRT、pfMDR1或pfDHFR)多态性,分析突变位点和方式及SNP基因频率等,并分析媒介按蚊对疟原虫可能的选择位点；然后分离抗性单虫株直接感染按蚊,并结合RNAi技术抑制按蚊重要免疫识别基因(TEP1等)表达,观察抗药相关基因经免疫缺陷蚊媒传播有无遗传变化,从而探讨蚊媒在恶性疟原虫抗药性选择性传播中的作用和机制。这有助于制定有效的阻断抗性传播措施，还为预测和控制恶性疟原虫药物抗性传播扩散提供新的思路。

Plasmodium falciparum drug resistance has become one of the most important barriers to malaria treatment and control, in addition to monitoring the Plasmodium falciparum drug resistance varation in human body, the selective spread of drug-resistant malaria parasite by the mosquito-borne was unclear. Recent studies have shown that in the vector selection pressures have an effect on pathogens and lead to phenotypic changes; Preliminary study found that chloroquine and mefloquine resistance of the plasmodium were changed by the mosquito-borne and the chloroquine resistance was increased, the mefloquine resistance was lost; Anopheles innate immunity may play an important role on this regard. Therefore, based on the preliminary studies, in this project we will use PCR-RFLP to observe Plasmodium falciparum resistance gene (pfCRT, pfMDR1,pfDHFR) polymorphism from human and Anopheles in malaria-endemic areas, analyze of the mutation site and ways and SNP gene frequency, and the choice sites on Plasmodium by the Anopheles;then separate Plasmodium falciparum resistance single strains to be directly infected Anopheles, and combine with RNAi to suppress expression of TEP1 and observe Plasmodium falciparum resistance gene change by the mosquito-borne, so as to explore the role and mechanism of the mosquito-borne Plasmodium falciparum resistance selective transmission. This helps to develop effective blocking resistance transmission measures, and also to predict and control the Plasmodium falciparum drug resistance transmission.