Nakazawa Shusuke, Maoka Takashi, Uemura Haruki, Ito Yoshihiro, Kanbara Hiroji
Institute of Tropical Medicine, Nagasaki University, Sakamoto 1-12-4, Nagasaki 852-8523, Japan.
Antimicrob Agents Chemother. 2002 Apr;46(4):958-65. doi: 10.1128/AAC.46.4.958-965.2002.
Recrudescences were simulated in vitro with drug treatment to examine how drug-sensitive parasites survive the treatment. Various numbers of cultured parasites were treated with lethal doses of pyrimethamine or mefloquine for various lengths of time. Recrudescences were observed in parasite populations with larger initial numbers of parasites when the treatment duration was prolonged. Equal numbers of parasitized erythrocytes were treated with various concentrations of pyrimethamine or mefloquine. There was no clear linear relationship between the incidence of recrudescence and the drug concentration. Parasites that had recrudesced were continuously allowed to recrudesce in the succeeding recrudescence experiments. Both the duration from the cessation of treatment to the time at which the recrudescent parasitemia level reached 1% and the growth rate of recrudescent parasites were equal among these recrudescences. The recrudescent parasites in these experiments were as sensitive to the drugs as the parasites tested before treatment were. These results suggest that a parasite culture may contain parasites in some phases that are not killed by drug for up to 10 days, which explains the recrudescences that occur even after treatment.
通过药物处理在体外模拟复发情况,以研究药物敏感寄生虫如何在治疗后存活。用致死剂量的乙胺嘧啶或甲氟喹对不同数量的培养寄生虫进行不同时长的处理。当处理时间延长时,初始寄生虫数量较多的寄生虫群体中观察到了复发情况。用不同浓度的乙胺嘧啶或甲氟喹处理等量的被寄生红细胞。复发发生率与药物浓度之间没有明显的线性关系。在后续的复发实验中,让已经复发的寄生虫持续复发。在这些复发情况中,从治疗停止到复发的寄生虫血症水平达到1%的持续时间以及复发寄生虫的生长速率都是相同的。这些实验中复发的寄生虫对药物的敏感性与治疗前测试的寄生虫相同。这些结果表明,寄生虫培养物中可能含有某些阶段的寄生虫,这些寄生虫在长达10天的时间内不会被药物杀死,这解释了即使在治疗后仍会出现复发的现象。