Teuscher Franka, Gatton Michelle L, Chen Nanhua, Peters Jennifer, Kyle Dennis E, Cheng Qin
Malaria Drug Resistance and Chemotherapy Laboratory, Queensland Institute of Medical Research, Australian Army Malaria Institute, Brisbane, Australia.
J Infect Dis. 2010 Nov 1;202(9):1362-8. doi: 10.1086/656476.
Despite the remarkable activity of artemisinin and its derivatives, monotherapy with these agents has been associated with high rates of recrudescence. The temporary arrest of the growth of ring-stage parasites (dormancy) after exposure to artemisinin drugs provides a plausible explanation for this phenomenon.
Ring-stage parasites of several Plasmodium falciparum lines were exposed to different doses of dihydroartemisinin (DHA) alone or in combination with mefloquine. For each regime, the proportion of recovering parasites was determined daily for 20 days.
Parasite development was abruptly arrested after a single exposure to DHA, with some parasites being dormant for up to 20 days. Approximately 50% of dormant parasites recovered to resume growth within the first 9 days. The overall proportion of parasites recovering was dose dependent, with recovery rates ranging from 0.044% to 1.313%. Repeated treatment with DHA or with DHA in combination with mefloquine led to a delay in recovery and an approximately 10-fold reduction in total recovery. Strains with different genetic backgrounds appeared to vary in their capacity to recover.
These results imply that artemisinin-induced arrest of growth occurs readily in laboratory-treated parasites and may be a key factor in P. falciparum malaria treatment failure.
尽管青蒿素及其衍生物具有显著活性，但使用这些药物进行单药治疗与高复发率相关。青蒿素类药物作用后，环状体期疟原虫生长的暂时停滞（休眠）为这一现象提供了一个合理的解释。
将几种恶性疟原虫株的环状体期疟原虫单独或与甲氟喹联合暴露于不同剂量的双氢青蒿素（DHA）。对于每种方案，在20天内每天测定复苏疟原虫的比例。
单次暴露于DHA后，疟原虫发育突然停止，一些疟原虫休眠长达20天。约50%的休眠疟原虫在最初9天内复苏并恢复生长。复苏疟原虫的总体比例呈剂量依赖性，恢复率在0.044%至1.313%之间。用DHA或DHA与甲氟喹联合重复治疗导致恢复延迟，总恢复率降低约10倍。具有不同遗传背景的菌株在恢复能力上似乎有所不同。
这些结果表明，青蒿素诱导的生长停滞在实验室处理的疟原虫中很容易发生，可能是恶性疟原虫疟疾治疗失败的关键因素。
