The development of drug resistance is a primary factor in the failure of malaria treatment strategies. For example, artemisinin is the drug most commonly used to treat human malaria worldwide, but some malaria parasites have developed resistance to it. Overcoming the development of resistance is therefore a key objective in the search for improved malaria treatments.

Researchers recently showed that treatment with the whole plant (Artemisia annua) from which artemisinin is derived could overcome existing resistance to artemisinin in a rodent malaria parasite. Moreover, the researchers estimated it would take at least three times longer for a second rodent malaria parasite to develop stable resistance to A. annua than to artemisinin. These data indicate that whole-plant therapy is more resilient to the development of resistance and therefore might have a longer effective 'lifespan' as a malaria treatment.

Stephen Rich (University of Massachusetts, Amherst) led the project to follow up on his group's earlier findings that A. annua was more effective than artemisinin in treating malaria in a rodent model. The new work specifically addressed resistance to A. annua versus artemisinin in two different rodent malaria parasites. “Conducting these experiments in different rodent malaria species...provides a robust test of the therapy,” Rich explained in a press release. His group chose an artemisinin-resistant strain of Plasmodium yoelii to test whether A. annua could overcome existing drug resistance and chose Plasmodium chabaudi to track the development of resistance because it most closely resembles the deadliest human malaria parasite, Plasmodium falciparum.

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In one set of experiments, mice were infected with an artemisinin-resistant strain of P. yoelii and then treated with high or low doses of A. annua or artemisinin. For each dose level, malaria parasitemia was lower in mice that received A. annua than in mice that received artemisinin (Proc. Natl. Acad. Sci. USA 112, 821–826; 2015). Next, Rich and colleagues used artificial selection experiments to monitor the development of resistance to A. annua or artemisinin in P. chabaudi under serial passage. Resistance to a low dose of artemisinin developed at passage 16, at which point the artemisinin dose was doubled; resistance to the high dose developed after an additional 24 passages. In contrast, resistance to a low dose of A. annua did not develop even after 49 passages. The researchers conclude that the antimalarial activity and resilience of A. annua offer compelling reasons to pursue the use of A. annua or other non-pharmaceutical forms of artemisinin for the treatment of human malaria.