缅甸青蒿素耐药恶性疟原虫的传播:K13分子标记物的横断面调查
Spread of artemisinin-resistant Plasmodium falciparum in Myanmar: a cross-sectional survey of the K13 molecular marker.
作者信息
Tun Kyaw M, Imwong Mallika, Lwin Khin M, Win Aye A, Hlaing Tin M, Hlaing Thaung, Lin Khin, Kyaw Myat P, Plewes Katherine, Faiz M Abul, Dhorda Mehul, Cheah Phaik Yeong, Pukrittayakamee Sasithon, Ashley Elizabeth A, Anderson Tim J C, Nair Shalini, McDew-White Marina, Flegg Jennifer A, Grist Eric P M, Guerin Philippe, Maude Richard J, Smithuis Frank, Dondorp Arjen M, Day Nicholas P J, Nosten François, White Nicholas J, Woodrow Charles J
机构信息
Myanmar Oxford Clinical Research Unit, Yangon, Myanmar; Defence Services Medical Research Centre, Naypyitaw, Myanmar.
Department of Molecular Tropical Medicine and Genetics, Mahidol University, Bangkok, Thailand; Mahidol Oxford Tropical Medicine Research Unit, Mahidol University, Bangkok, Thailand.
出版信息
Lancet Infect Dis. 2015 Apr;15(4):415-21. doi: 10.1016/S1473-3099(15)70032-0. Epub 2015 Feb 20.
BACKGROUND
Emergence of artemisinin resistance in southeast Asia poses a serious threat to the global control of Plasmodium falciparum malaria. Discovery of the K13 marker has transformed approaches to the monitoring of artemisinin resistance, allowing introduction of molecular surveillance in remote areas through analysis of DNA. We aimed to assess the spread of artemisinin-resistant P falciparum in Myanmar by determining the relative prevalence of P falciparum parasites carrying K13-propeller mutations.
METHODS
We did this cross-sectional survey at malaria treatment centres at 55 sites in ten administrative regions in Myanmar, and in relevant border regions in Thailand and Bangladesh, between January, 2013, and September, 2014. K13 sequences from P falciparum infections were obtained mainly by passive case detection. We entered data into two geostatistical models to produce predictive maps of the estimated prevalence of mutations of the K13 propeller region across Myanmar.
FINDINGS
Overall, 371 (39%) of 940 samples carried a K13-propeller mutation. We recorded 26 different mutations, including nine mutations not described previously in southeast Asia. In seven (70%) of the ten administrative regions of Myanmar, the combined K13-mutation prevalence was more than 20%. Geospatial mapping showed that the overall prevalence of K13 mutations exceeded 10% in much of the east and north of the country. In Homalin, Sagaing Region, 25 km from the Indian border, 21 (47%) of 45 parasite samples carried K13-propeller mutations.
INTERPRETATION
Artemisinin resistance extends across much of Myanmar. We recorded P falciparum parasites carrying K13-propeller mutations at high prevalence next to the northwestern border with India. Appropriate therapeutic regimens should be tested urgently and implemented comprehensively if spread of artemisinin resistance to other regions is to be avoided.
FUNDING
Wellcome Trust-Mahidol University-Oxford Tropical Medicine Research Programme and the Bill & Melinda Gates Foundation.
背景
东南亚出现的青蒿素耐药性对全球恶性疟原虫疟疾的控制构成严重威胁。K13标记物的发现改变了青蒿素耐药性监测方法,通过DNA分析使得在偏远地区开展分子监测成为可能。我们旨在通过确定携带K13螺旋桨突变的恶性疟原虫的相对流行率,评估缅甸青蒿素耐药性恶性疟原虫的传播情况。
方法
2013年1月至2014年9月期间,我们在缅甸十个行政区的55个疟疾治疗中心以及泰国和孟加拉国的相关边境地区开展了这项横断面调查。恶性疟原虫感染的K13序列主要通过被动病例检测获得。我们将数据输入两个地理统计模型,以生成缅甸K13螺旋桨区域突变估计流行率的预测地图。
结果
总体而言,940个样本中有371个(39%)携带K13螺旋桨突变。我们记录到26种不同的突变, 包括9种东南亚地区此前未描述过的突变。在缅甸十个行政区中的七个(70%),K13突变的综合流行率超过20%。地理空间绘图显示,该国东部和北部大部分地区K13突变的总体流行率超过10%。在实皆省距印度边境25公里的霍马林,45个寄生虫样本中有21个(47%)携带K13螺旋桨突变。
解读
青蒿素耐药性在缅甸大部分地区存在。我们在与印度接壤的西北边境附近记录到携带K13螺旋桨突变的恶性疟原虫的高流行率。若要避免青蒿素耐药性传播到其他地区,应紧急测试并全面实施适当的治疗方案。
资金来源
惠康信托基金会 - 玛希隆大学 - 牛津热带医学研究项目以及比尔及梅琳达·盖茨基金会。