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Plasmodium falciparum in vitro continuous culture conditions: A comparison of parasite susceptibility and tolerance to anti-malarial drugs throughout the asexual intra-erythrocytic life cycle

机译:体外连续培养条件下的恶性疟原虫:无性红细胞内无生命周期中寄生虫敏感性和对抗疟疾药物的耐受性比较

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摘要

The continuous culture of Plasmodium falciparum is often seen as a means to an end, that end being to probe the biology of the parasite in question, and ultimately for many in the malaria drug discovery arena, to identify means of killing the parasite in order to treat malaria. In vitro continuous culture of Plasmodium falciparum is a fundamental requirement when undertaking malaria research where the primary objectives utilise viable parasites of a desired lifecycle stage. This investigation, and resulting data, compared the impact culturing Plasmodium falciparum long term (4 months) in different environmental conditions had on experimental outcomes and thus conclusions. The example presented here focused specifically on the effect culture conditions had on the in vitro tolerance of Plasmodium falciparum to standard anti-malarial drugs, including artemisinin and lumefantrine. Historical data from an independent experiment for 3D7-ALB (5% O2) was also compared with that obtained from this study. We concluded that parasites cultured for several months in media supplemented with a serum substitute such as Albumax II® or within hyperoxic conditions (21% O2), demonstrate highly variable responses to artemisinin and lumefantrine but not all anti-malarial drugs, when compared to those cultured in human serum in combination with Albumax II® under normoxic conditions (5% O2) for the parasite.
机译:恶性疟原虫的连续培养通常被认为是达到目的的一种手段,该目的是探究有关寄生虫的生物学特性,并最终在疟疾药物发现领域寻找许多寄生虫,从而确定杀死寄生虫的手段,从而治疗疟疾。在进行疟疾研究时,恶性疟原虫的体外连续培养是一项基本要求,其中主要目标是利用所需生命周期阶段的可行寄生虫。这项研究和所得数据比较了在不同环境条件下长期(4个月)培养恶性疟原虫对实验结果和结论的影响。这里提供的示例专门针对培养条件对恶性疟原虫对标准抗疟药(包括青蒿素和lumantantrine)的体外耐受性的影响。还比较了独立实验中3D7-ALB(5%O2)的历史数据与本研究获得的历史数据。我们得出的结论是,寄生虫在补充有血清替代品(如Albumax II ®)的培养基中或在高氧条件下(21%O2)培养了几个月,显示出对青蒿素和lumefantrine的高度可变反应,但并非所有抗与在常氧条件下(5%O2)寄生虫在人血清中与Albumax II ®组合培养的疟疾药物相比。

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