Dried whole-plant Artemisia annua slows evolution of malaria drug resistance and overcomes resistance to artemisinin
Edited* by Francisco J. Ayala, University of California, Irvine, CA, and approved December 5, 2014 (received for review July 10, 2014)
Significance
Evolution 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.
Abstract
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.
Acknowledgments
We thank Ricardo Gazzinelli (University of Massachusetts Medical School), Doug Golenbock (University of Massachusetts Medical School), and Guang Xu (University of Massachusetts, Amherst) for assistance and advice in conducting experiments. We also thank the Worcester Polytechnic Institute and the University of Massachusetts Center for Clinical and Translational Science (CCTS-20110001) for funding this project.
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Published online: January 5, 2015
Published in issue: January 20, 2015
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Acknowledgments
We thank Ricardo Gazzinelli (University of Massachusetts Medical School), Doug Golenbock (University of Massachusetts Medical School), and Guang Xu (University of Massachusetts, Amherst) for assistance and advice in conducting experiments. We also thank the Worcester Polytechnic Institute and the University of Massachusetts Center for Clinical and Translational Science (CCTS-20110001) for funding this project.
Notes
*This Direct Submission article had a prearranged editor.
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The authors declare no conflict of interest.
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Cite this article
Dried whole-plant Artemisia annua slows evolution of malaria drug resistance and overcomes resistance to artemisinin, Proc. Natl. Acad. Sci. U.S.A.
112 (3) 821-826,
https://doi.org/10.1073/pnas.1413127112
(2015).
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