Is Artemisia tea a monotherapy?
Yesterday, I wrote in Slate about the use of Artemisia annua tea to prevent and treat malaria in Uganda. It's a complicated a topic, and I've gotten some tough questions in the comments and on Twitter about whether it will lead to resistance to artemisinin-combination therapies (ACTs).
There are strong arguments on both sides. It's worth considering that when artemisinin-based drugs first came out there were people who argued that they should be reserved for life-threatening cases, but they are now considered the first-line treatment for uncomplicated malaria in parts of Africa and Asia. Those in favor of using the drug more broadly argued that by combining an artemisinin with a second drug with a different mode of action, resistance would be unlikely to evolve. The key question, then, is what is the difference between a proper ACT and a tea made from a single plant? In other words, is Artemisia tea a monotherapy or a combination therapy?
Pure artemisinin is the most studied antimalarial compound in the plant, but there are suggestions that a variety of compounds contribute to its parasite-killing properties. Writing in PLoS ONE last year, one group of authors christened Artemisia tea, a pACT, which stands for plant Artemesinin combination therapy:
Two other major A. annua flavonoids, myricetin and quercetin, are known to inhibit mammalian thioredoxin reductase, which is critical for cellular redox control . Thioredoxin reductase is also essential for the P. falciparum erythrocytic stage ; therefore, inhibition of this parasite enzyme by myricetin and quercetin may work in synergy with artemisinin against P. falciparum.
In addition to the bioavailability and potentiation attributes of WP, there are other compounds inA. annua that may act to reduce parasitemia independent of artemisinin. Liu et al (1992) reported the antimalarial activity of several A. annua flavonoids delivered in vitro as isolated compounds, in the absence of artemisinin . Moreover, antimalarial activity has been documented for related plant species that do not produce artemisinin . Among the compounds in A. annua not yet fully investigated are more than a dozen other sesquiterpenes, some of which have shown promise for killing parasites in rodent models .
Determining the mechanisms for increased efficacy of WP will require further investigation, but it seems certain that the constituent compounds contained within A. annua comprise a complex set of interactions and synergies yet to be described. Given the complex nature of the plant and its many components, WP may not necessarily be considered a simple monotherapy. While the temptation might be to consider WP as merely an alternative delivery mechanism for artemisinin, our results strongly indicate that WP is unique and may represent an innovative combination therapy. We refer to this as a plant Artemisinin Combination Therapy (pACT). A pACT can be distinguished from other combinational therapies where the drug components do not necessarily work synergistically because their combinations are artificially contrived. The pACT comprises a biologically complex entity, in which the combinations are result of evolutionary processes that would have attributes of redundancy and resiliency that make combination therapies selectively advantageous to simple monotherapies. Refinements of these combinations by evolutionary processes ensures they are robust.
This is, of course, all speculation based on their impressive results in rats. No one has conducted a clinical trial on these other pure compounds in Artemisia annua, and without digging through the specific literature, it is fair to say that "anti-malarial activity" is a rather common property in the plant kingdom. What matters is whether these other compounds are potent enough to qualify as a combination therapy.
In the end, the goal of my Slate piece was to stimulate the conversation about how life-saving therapies are researched, developed, and distributed in the developing world. The use of this tea is both frightening and exciting. Over the next year, I'll continue to explore where traditional medicine and ethnobotany fit into current medical paradigms.