云南及其境外周边科泰复治疗恶性疟原虫无性体转阴时间延长分子基础研究

项目名称： 云南及其境外周边科泰复治疗恶性疟原虫无性体转阴时间延长分子基础研究

项目编号： No.81673113

项目类型： 面上项目

立项/批准年度： 2017

项目学科： 医药、卫生

项目作者： 刘慧

作者单位： 云南省寄生虫病防治所

项目金额： 25万元

中文摘要： 青蒿素是目前全世界治疗疟疾最有效的药物，但中缅边境地区科泰复治疗恶性疟原虫无性体转阴时间已显著延长，大湄公河次区域（GMS）除中国外，其余5国恶性疟原虫对青蒿素抗性已被证实。为有效遏制青蒿素抗性发展和扩散，本研究拟通过双氢青蒿素哌喹片临床疗效试验、建立恶性疟原虫实验室虫株，然后开展双氢青蒿素和哌喹单药分别处理体外培养恶性疟原虫环状体存活实验，实时掌握云南及境外周边恶性疟原虫对科泰复敏感性变化，研究清楚云南及境外周边无性体清除时间延长原因，即是双氢青蒿素还是哌喹单药敏感性下降，还是两者均下降；并进一步通过PCR实验和DNA测序，找到治疗恶性疟原虫无性体转阴时间延长分子标志，为中国和GMS疟疾消除及消除成果巩固提供科学依据和技术支撑。

中文关键词： 恶性疟原虫；青蒿素抗性；哌喹敏感性；分子标记；无性体转阴时间

英文摘要： Artemisinin is the most efficacious drug for malaria treatment in the world. However, significantly delayed asexual parasite clearance times have been confirmed along China-Myanmar border. In the Great Mekong Sub-region (GMS), five countries had confirmed artemisinin resistance except China. In order to contain development and spread of artemisinin resistance, the project proposes to conduct clinically therapeutic efficacy of dihydroartemisinin-piperaquine (DHA-PPQ), establishing laboratory strains of Plasmodium falciparum, in-vitro survival assays of P. falciparum after respectively exposing to single DHA and PPQ. These researches will make clear the changing sensitivity of P. falciparum to DHA-PPQ in time, the cause of delayed asexual parasite clearance times in treatment of Plasmodium falciparum malaria with DHA-PPQ, i.e. reduced sensitivity of DHA or PPQ or both DHA and PPQ in Yunnan and neighboring areas of other countries. Furthermore, polymerase chain reaction (PCR) test and sequencing of DNA will be conducted to type and look for molecular markers for the delayed asexual parasite clearance times in treatment of Plasmodium falciparum malaria with DHA-PQ. The results of these researches will contribute to eliminating malaria and maintaining achievement of malaria elimination by providing scientific evidences and technical support in China and other areas of GMS.

英文关键词： Plasmodium falciparum ;artemisinin resistance;piperaquine sensitivity;molecular marker;asexual parasite clearance time