Le Bras J, Deloron P, Ricour A, Andrieu B, Savel J, Coulaud J P
Exp Parasitol. 1983 Aug;56(1):9-14. doi: 10.1016/0014-4894(83)90091-7.
Fifteen strains of Plasmodium falciparum have been cultivated since 1979 using the Trager and Jensen method of continuous culture on isolates from malaria patients. One hundred and two drug sensitivity studies have been carried out on these strains using a semimicro test. Three isolates, initially resistant to chloroquine, adapted rapidly to in vitro cultivation and maintained their high level of resistance (ED50 above 660 nM). Eleven isolates, initially chloroquine sensitive (ED50 under 90 nM) became resistant to this drug (ED50 = 190 to 1950 nM) after the 2-15 weeks required for their adaptation to continuous culture. The resistance of these strains never decreased during the following 15 months of continuous culture. The sensitivity to quinine varied initially from one strain to another (ED50 = 160 to 660 nM) and fluctuated during cultivation in the ratio of 1:3.5 for a given strain. The sensitivity of mefloquine remained high for all strains (ED50 under 150 nM) but one (ED50 = 560 nM). These results suggest that there might be a relationship between in vitro adaptation to culture of P. falciparum by the Trager-Jensen method and a chloroquine-resistant characteristic of the strain. There is the possibility of the emergence of a drug-resistant subpopulation or of changes in the metabolic pathways.
自1979年以来，利用特拉格和詹森的连续培养方法，对疟疾患者的分离株进行培养，已培养出15株恶性疟原虫。使用半微量试验对这些菌株进行了102次药物敏感性研究。有3株最初对氯喹耐药的菌株，能迅速适应体外培养，并维持其高度耐药性（半数有效剂量高于660 nM）。11株最初对氯喹敏感（半数有效剂量低于90 nM）的菌株，在适应连续培养所需的2至15周后，对该药物产生了耐药性（半数有效剂量为190至1950 nM）。在随后连续培养的15个月中，这些菌株的耐药性从未降低。对奎宁的敏感性最初因菌株而异（半数有效剂量为160至660 nM），并且在培养过程中，对于给定的菌株，其波动比例为1:3.5。除了一株（半数有效剂量 = 560 nM）之外，所有菌株对甲氟喹的敏感性仍然很高（半数有效剂量低于150 nM）。这些结果表明，通过特拉格 - 詹森方法在体外适应培养的恶性疟原虫与该菌株的氯喹耐药特性之间可能存在关联。有可能出现耐药亚群或代谢途径发生变化。
