Department of Tropical Medicine and Malaria, Research Institute, National Centre for Global Health and Medicine, 1-21-1 Toyama, Shinjuku, Tokyo, 162-8655, Japan.
SATREPS Project (JICA/AMED) for Parasitic Diseases, Vientiane, Lao People's Democratic Republic.
Malar J. 2018 Dec 27;17(1):483. doi: 10.1186/s12936-018-2625-6.
The emergence and transnational spread of artemisinin resistance in Plasmodium falciparum in the Greater Mekong Sub-region (GMS) is a serious threat to malaria elimination in the region and could present a threat to malaria control in Africa. Recently, the Lao Government adopted the goal of malaria elimination by 2030, for which monitoring of artemisinin-resistant malaria within the country is indispensable. This study's objectives were to assess the distribution of k13 mutations in Laos.
Plasmodium falciparum isolates (n = 1151) were collected from five southern provinces in Laos between 2015 and 2016, and three isolates from the northernmost province bordering China in 2017. Polymorphisms of the k13 gene and two flanking regions were analysed to estimate relationship among the isolates.
In the five southern provinces, overall 55.5% of the isolates possessed artemisinin-resistant mutations of the k13 gene (C580Y, P574L, R539T, Y493H). The C580Y was the predominant mutation (87.2%). The frequencies of the k13 mutations were heterogeneous in the five southern provinces, but with a clear tendency showing the highest frequency in the south (72.5%) and to a lower degree when moving northward (28.0%). The three isolates from the Lao-Chinese border also possessed the C580Y mutation. Analysis of the flanking loci demonstrated that these three isolates were genetically very close to resistant strains originating from western Cambodia.
Artemisinin resistance was observed to be rapidly increasing and spreading northwards through Laos and has now reached the Chinese border. The Lao and Chinese governments, as well as the international community, should make dedicated efforts to contain the spread of k13 mutations within Laos and in the GMS.
恶性疟原虫对青蒿素的耐药性在大湄公河次区域（GMS）的出现和跨国传播对该地区的疟疾消除构成了严重威胁，并可能对非洲的疟疾控制构成威胁。最近，老挝政府通过了到 2030 年消除疟疾的目标，为此，在该国境内监测青蒿素耐药性是必不可少的。本研究的目的是评估老挝境内 k13 突变的分布。
2015 年至 2016 年间，从老挝五个南部省份采集了 1151 株恶性疟原虫分离株，2017 年从与中国接壤的最北部省份采集了 3 株分离株。分析了 k13 基因和两个侧翼区的多态性，以估计分离株之间的关系。
在五个南部省份，总体上有 55.5%的分离株具有青蒿素耐药性的 k13 基因突变（C580Y、P574L、R539T、Y493H）。C580Y 是主要突变（87.2%）。五个南部省份的 k13 突变频率存在异质性，但从南向北的频率呈明显的趋势，南部最高（72.5%），向北逐渐降低（28.0%）。从老挝-中国边境采集的三个分离株也携带 C580Y 突变。侧翼位点分析表明，这三个分离株与来自柬埔寨西部的耐药株在遗传上非常接近。
青蒿素耐药性在老挝迅速增加并向北传播，现已到达中国边境。老挝和中国政府以及国际社会应共同努力，遏制老挝境内和大湄公河次区域 k13 突变的传播。
