Iwagami Moritoshi, Tangpukdee Noppadon, Wilairatana Polrat, Krudsood Srivicha, Dao Le Duc, Nakazawa Shusuke, Sinuon Muth, Socheat Duong, Yasuoka Junko, Jimba Masamine, Watanabe Hisami, Kobayashi Jun, Toma Hiromu, Vanisaveth Viengxay, Hongvanthong Bouasy, Brey Paul T, Kano Shigeyuki
Department of Tropical Medicine and Malaria, National Center for Global Health and Medicine, Research Institute, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan; Ministry of Health, Institut Pasteur du Laos, Vientiane, Laos; SATREPS Project for Parasitic Diseases, Vientiane, Laos.
Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
Parasitol Int. 2018 Dec;67(6):816-823. doi: 10.1016/j.parint.2018.08.008. Epub 2018 Aug 28.
Malaria morbidity and mortality have decreased gradually in the Greater Mekong Subregion (GMS). Presently, WHO sets a goal to eliminate malaria by 2030 in the GMS. However, drug-resistant malaria has been reported from several endemic areas. To achieve the goal of elimination, the status of the emergence and spread of drug resistance should be monitored. In this study, the genotype of the Plasmodium falciparum chloroquine (CQ) resistance transporter gene (pfcrt) and 6 microsatellite DNA loci flanking the gene were examined. P. falciparum isolates (n = 136) was collected from malaria patients in Thailand (n = 50, 2002-2005), Vietnam (n = 39, 2004), Laos (n = 15, 2007) and Cambodia (n = 32, 2009). Amino acid sequences at codons 72-76 on the gene were determined. All of the isolates from Thailand were CQ-resistant (CVIET), as were all of the isolates from Cambodia (CVIET, CVIDT). Thirteen of the 15 isolates (87%) from Laos were CQ-resistant (CVIET, CVIDT), whereas the other 2 (13%) were CQ-susceptible (CVMNK). In contrast, 27 of the 39 isolates (69%) from Vietnam were CQ-susceptible (CVMNK), whereas the other 12 (31%) were CQ-resistant (CVIET, CVIDT, CVMDT) or mixed (CVMNK/CVIDT). The mean of expected heterozygosity of the microsatellite loci was 0.444 in the Thai population, 0.482 in the Cambodian population, and 0.734 in the Vietnamese population. Genetic diversity in the Thai population was significantly lower than that in the Vietnamese population. These results suggested that chloroquine selective pressure on P. falciparum populations is heterogeneous in the GMS. Therefore, further examination to understand the mechanisms behind the emergence and spread of drug-resistant malaria are needed.
大湄公河次区域（GMS）的疟疾发病率和死亡率已逐渐下降。目前，世界卫生组织设定了到2030年在GMS消除疟疾的目标。然而，几个疟疾流行地区已报告了耐药性疟疾。为实现消除目标，应监测耐药性的出现和传播情况。在本研究中，检测了恶性疟原虫氯喹（CQ）抗性转运蛋白基因（pfcrt）的基因型及其侧翼的6个微卫星DNA位点。从泰国（n = 50，2002 - 2005年）、越南（n = 39，2004年）、老挝（n = 15，2007年）和柬埔寨（n = 32，2009年）的疟疾患者中收集了恶性疟原虫分离株（n = 136）。确定了该基因第72 - 76位密码子的氨基酸序列。泰国的所有分离株均对氯喹耐药（CVIET），柬埔寨的所有分离株也是如此（CVIET，CVIDT）。老挝的15株分离株中有13株（87%）对氯喹耐药（CVIET，CVIDT），而另外2株（13%）对氯喹敏感（CVMNK）。相比之下，越南的39株分离株中有27株（69%）对氯喹敏感（CVMNK），而另外12株（31%）对氯喹耐药（CVIET，CVIDT，CVMDT）或为混合类型（CVMNK/CVIDT）。微卫星位点的预期杂合度均值在泰国人群中为0.444，在柬埔寨人群中为0.482，在越南人群中为0.734。泰国人群的遗传多样性显著低于越南人群。这些结果表明，GMS中恶性疟原虫群体受到的氯喹选择压力是异质性的。因此，需要进一步研究以了解耐药性疟疾出现和传播背后的机制。
