Gresty Karryn J, Gray Karen-Ann, Bobogare Albino, Taleo George, Hii Jeffrey, Wini Lyndes, Cheng Qin, Waters Norman C
Australian Army Malaria Institute, Enoggera, Brisbane, Queensland, Australia.
Malar J. 2014 Oct 15;13:406. doi: 10.1186/1475-2875-13-406.
Chloroquine (CQ), alone or in combination with sulphadoxine-pyrimethamine, was widely used for the treatment of Plasmodium falciparum and Plasmodium vivax for several decades in both Vanuatu and Solomon Islands prior to the introduction of artemether-lumefantrine (AL) in 2008. However, the effect of chloroquine selection on parasite population, which may affect the efficacy of lumefantrine or other partner drugs of artemisinin, has not been well assessed. This study aims to provide baseline data on molecular markers (pfcrt and pfmdr1), along with the origins of pfcrt, prior to the introduction of AL.
Blood spots were obtained from epidemiological surveys conducted on Tanna Island, Tafea Province, Vanuatu and Temotu Province, Solomon Islands in 2008. Additional samples from Malaita Province, Solomon Islands were collected as part of an artemether-lumefantrine efficacy study in 2008. Plasmodium falciparum pfcrt and pfmdr1 genes were examined for polymorphisms. Microsatellite markers flanking pfcrt were also examined to ascertain origins of CQ resistance.
Pfcrt analysis revealed 100% of parasites from Tafea Province, Vanuatu and Malaita Province, Solomon Islands and 98% of parasites from Temotu Province, Solomon Islands carried the K76T polymorphism that confers CQ resistance. Comparison of pfcrt allelic patterns and microsatellite markers flanking pfcrt revealed six haplotypes with more than 70% of isolates possessing haplotypes very similar to those observed in Papua New Guinea. The dominant (98.5%) pfmdr1 allele across all island groups was YYCND.
Prior to the introduction of AL in the Solomon Islands and Vanuatu, P. falciparum isolates possessed point mutations known to confer CQ resistance and possibly associated with a decreased susceptibility to quinine and halofantrine, but an increased susceptibility to artemisinin and lumefantrine. Overall, pfcrt allelic types and the flanking microsatellite markers exhibited similarities to those of Papua New Guinea, suggesting these parasites share a common ancestry. The current use of AL for both P. falciparum and P. vivax infections will enable changes in these markers, in the absence of CQ pressure, to be monitored.
在2008年引入蒿甲醚-本芴醇（AL）之前的几十年里，氯喹（CQ）单独或与磺胺多辛-乙胺嘧啶联合使用，在瓦努阿图和所罗门群岛被广泛用于治疗恶性疟原虫和间日疟原虫。然而，氯喹选择对寄生虫种群的影响，可能会影响本芴醇或其他青蒿素联合用药的疗效，尚未得到充分评估。本研究旨在提供关于分子标记物（pfcrt和pfmdr1）的基线数据，以及在引入AL之前pfcrt的起源。
血斑取自2008年在瓦努阿图塔菲亚省塔纳岛以及所罗门群岛特莫图省进行的流行病学调查。作为2008年蒿甲醚-本芴醇疗效研究的一部分，还收集了所罗门群岛马莱塔省的额外样本。检测恶性疟原虫pfcrt和pfmdr1基因的多态性。还检测了pfcrt侧翼的微卫星标记，以确定氯喹抗性的起源。
pfcrt分析显示，来自瓦努阿图塔菲亚省和所罗门群岛马莱塔省的100%的寄生虫，以及来自所罗门群岛特莫图省的98%的寄生虫携带赋予氯喹抗性的K76T多态性。pfcrt等位基因模式与pfcrt侧翼微卫星标记的比较显示有六种单倍型，超过70%的分离株具有与在巴布亚新几内亚观察到的非常相似的单倍型。所有岛屿组中占主导地位（98.5%）的pfmdr1等位基因为YYCND。
在所罗门群岛和瓦努阿图引入AL之前，恶性疟原虫分离株具有已知赋予氯喹抗性的点突变，可能与对奎宁和卤泛群敏感性降低有关，但对青蒿素和本芴醇敏感性增加。总体而言，pfcrt等位基因类型及其侧翼微卫星标记与巴布亚新几内亚的相似，表明这些寄生虫有共同的祖先。目前对恶性疟原虫和间日疟原虫感染均使用AL，将能够在没有氯喹压力的情况下监测这些标记物的变化。
