Monday, 24 August 2015

Dried whole-plant Artemisia annua slows evolution of malaria drug resistance and overcomes resistance to artemisinin

Mostafa A. Elfawala, Melissa J. Towlerb, Nicholas G. Reichc, Pamela J. Weathersb, and Stephen M. Richa,1
aLaboratory of Medical Zoology, Department of Microbiology, University of Massachusetts, Amherst, MA 01003; bDepartment of Biology and Biotechnology,
Worcester Polytechnic Institute, Worcester, MA 01609; and cDivision of Biostatistics and Epidemiology, School of Public Health and Health Sciences,
University of Massachusetts, Amherst, MA 01003
Edited* by Francisco J. Ayala, University of California, Irvine, CA, and approved December 5, 2014 (received for review July 10, 2014)

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.