title: Dried whole-plant Artemisia annua slows evolution of malaria drug resistance and overcomes resistance to artemisinin.
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.
authors.affiliation: Laboratory of Medical Zoology, Department of Microbiology, University of Massachusetts, Amherst, MA 01003;
authors.forename: Mostafa A
authors.initials: MA
authors.lastname: Elfawal
authors.affiliation: Department of Biology and Biotechnology, Worcester Polytechnic Institute, Worcester, MA 01609; and.
authors.forename: Melissa J
authors.initials: MJ
authors.lastname: Towler
authors.affiliation: Division of Biostatistics and Epidemiology, School of Public Health and Health Sciences, University of Massachusetts, Amherst, MA 01003.
authors.forename: Nicholas G
authors.initials: NG
authors.lastname: Reich
authors.affiliation: Department of Biology and Biotechnology, Worcester Polytechnic Institute, Worcester, MA 01609; and.
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Weathers
authors.affiliation: Laboratory of Medical Zoology, Department of Microbiology, University of Massachusetts, Amherst, MA 01003; smrich@umass.edu.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Rich
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D031172:Artemisia annua / Q000737:chemistry*; D037621:Artemisinins / Q000494:pharmacology*; D004351:Drug Resistance; D051379:Mice
chemical_list: D000962:Antimalarials; D037621:Artemisinins; C031327:artemisinin
keywords: Plasmodium; artemisinin; drug resistance; evolution; malaria