Mungthin Mathirut, Watanatanasup Ekularn, Sitthichot Naruemon, Suwandittakul Nantana, Khositnithikul Rommanee, Ward Stephen A
Department of Parasitology, Phramongkutklao College of Medicine, Bangkok, Thailand.
Mahidol University International College, Nakhon Pathom, Thailand.
Am J Trop Med Hyg. 2017 Mar;96(3):624-629. doi: 10.4269/ajtmh.16-0668. Epub 2017 Apr 6.
Piperaquine combined with dihydroartemisinin is one of the artemisinin derivative combination therapies, which can replace artesunate-mefloquine in treating uncomplicated falciparum malaria in Thailand. The aim of this study was to determine the in vitro sensitivity of Thai isolates against piperaquine and the influence of the gene on in vitro response. One hundred and thirty-seven standard laboratory and adapted Thai isolates of were assessed for in vitro piperaquine sensitivity. Polymorphisms of the gene were determined by polymerase chain reaction methods. The mean and standard deviation of the piperaquine IC in Thai isolates of were 16.7 ± 6.3 nM. The parasites exhibiting chloroquine IC of ≥ 100 nM were significantly less sensitive to piperaquine compared with the parasite with chloroquine IC of < 100 nM. No significant association between the copy number and piperaquine IC values was found. In contrast, the parasites containing the 86Y allele exhibited significantly reduced piperaquine sensitivity. Before nationwide implementation of dihydroartemisinin-piperaquine as the first-line treatment in Thailand, in vitro and in vivo evaluations of this combination should be performed especially in areas where parasites containing the 86Y allele are predominant such as the Thai-Malaysian border.
双氢青蒿素哌喹是青蒿素类复方疗法之一,可在泰国替代青蒿琥酯-甲氟喹治疗非复杂性恶性疟。本研究旨在确定泰国疟原虫分离株对哌喹的体外敏感性以及该基因对体外反应的影响。对137株标准实验室培养及适应性培养的泰国疟原虫分离株进行了哌喹体外敏感性评估。采用聚合酶链反应方法测定该基因的多态性。泰国疟原虫分离株中哌喹IC的平均值和标准差为16.7±6.3 nM。与氯喹IC<100 nM的疟原虫相比,氯喹IC≥100 nM的疟原虫对哌喹的敏感性显著降低。未发现该基因拷贝数与哌喹IC值之间存在显著关联。相反,含有86Y等位基因的疟原虫对哌喹的敏感性显著降低。在泰国全国范围内将双氢青蒿素哌喹作为一线治疗药物实施之前,尤其应在含有86Y等位基因的疟原虫占主导的地区(如泰国-马来西亚边境)对该联合用药进行体外和体内评估。