期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2015
卷号：112
期号：3
页码：821-826
DOI：10.1073/pnas.1413127112
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceEvolution of malaria parasite drug resistance has thwarted efforts to control this deadly disease. Use of drug combinations has been proposed to slow that evolution. Artemisinin is a favorite drug in the global war on malaria and is frequently used in combination therapies. Here we show that using the whole plant (Artemisia annua) from which artemisinin is derived can overcome parasite resistance and is actually more resilient to evolution of parasite resistance; i.e., parasites take longer to evolve resistance, thus increasing the effective life span of the therapy. Pharmaceutical monotherapies against human malaria have proven effective, although ephemeral, owing to the inevitable evolution of resistant parasites. Resistance to two or more drugs delivered in combination will evolve more slowly; hence combination therapies have become the preferred norm in the fight against malaria. At the forefront of these efforts has been the promotion of Artemisinin Combination Therapy, but despite these efforts, resistance to artemisinin has begun to emerge. In 2012, we demonstrated the efficacy of the whole plant (WP)--not a tea, not an infusion--as a malaria therapy and found it to be more effective than a comparable dose of pure artemisinin in a rodent malaria model. Here we show that WP overcomes existing resistance to pure artemisinin in the rodent malaria Plasmodium yoelii. Moreover, in a long-term artificial selection for resistance in Plasmodium chabaudi, we tested resilience of WP against drug resistance in comparison with pure artemisinin (AN). Stable resistance to WP was achieved three times more slowly than stable resistance to AN. WP treatment proved even more resilient than the double dose of AN. The resilience of WP may be attributable to the evolutionary refinement of the plant's secondary metabolic products into a redundant, multicomponent defense system. Efficacy and resilience of WP treatment against rodent malaria provides compelling reasons to further explore the role of nonpharmaceutical forms of AN to treat human malaria.
关键词：malaria ; drug resistance ; artemisinin ; Plasmodium ; evolution
