Artemisinin‐induced dormancy in plasmodium falciparum: duration, recovery rates, and implications in treatment failure.
Artemisinin‐induced dormancy in plasmodium falciparum: duration, recovery rates, and implications in treatment failure.
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DOI：
10.1086/656476
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发表时间：
2010-11-01
期刊：
影响因子：
--
通讯作者：
Cheng Q
中科院分区：
文献类型：
--
作者：
Teuscher F;Gatton ML;Chen N;Peters J;Kyle DE;Cheng Q
尽管青蒿素及其衍生物具有显着的活性，但它们的单一疗法与高复发率有关。接触青蒿素药物后环期寄生虫的暂时生长停滞（休眠）为这种现象提供了合理的解释。将几种恶性疟原虫品系的环期寄生虫暴露于不同剂量的单独的二氢青蒿素（DHA）或与甲氟喹（MQ）的组合。对于每种方案，在 20 天内每天测定寄生虫恢复的比例。一次接触 DHA 后，寄生虫的发育就会突然停止，一些寄生虫会休眠长达 20 天。大约 50% 的休眠寄生虫在前 9 天内恢复生长。寄生虫恢复的总体比例与剂量相关，恢复率范围为 0.044% 至 1.313%。重复使用 DHA 或 DHA 与 MQ 联合治疗会导致恢复延迟，总恢复率下降约 10 倍。具有不同遗传背景的菌株的恢复能力似乎有所不同。这些结果表明青蒿素诱导的生长停滞很容易发生在实验室治疗的寄生虫中，并且可能是恶性疟原虫疟疾治疗失败的关键因素。
Despite the remarkable activity of artemisinin and its derivatives their monotherapy has been associated with high rates of recrudescence. The temporary growth arrest of ring stage parasites (dormancy) following exposure to artemisinin drugs provides a plausible explanation for this phenomenon. Ring stage parasites of several P. falciparum lines were exposed to different doses of dihydroartemisinin (DHA) alone or in combination with mefloquine (MQ). For each regime the proportion of parasites recovering was determined daily for 20 days. Parasite development was abruptly arrested following 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 dependant with recovery rates ranging from 0.044% to 1.313%. Repeated treatment with DHA, or DHA in combination with MQ, led to a delay in recovery and a ~10 fold reduction in total recovery. Strains with different genetic backgrounds appear to vary in their capacity to recover. These results imply that artemisinin-induced growth arrest occurs readily in laboratory treated parasites, and may be a key factor in treatment failure of P. falciparum malaria.
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影响因子：
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DOI：
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发表时间：
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影响因子：
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