Why has malaria only now started to develop resistance against artemisinin, considering the compound has been in use for about two millennia in its herbal form in China?

The WHO has reported:

In recent years, parasite resistance to artemisinins has been detected in four countries of the Greater Mekong subregion: Cambodia, Myanmar, Thailand and Viet Nam.

However, the compound artemisinin has been used in its herbal form since at least around 400AD, when it was documented in the well known medical text 肘后方.

What are some reasons that malaria has only begun developing resistance now?

I would imagine that modern artemisinin would be more effective in completely eliminating malaria, as compared to use in its traditional herbal form. This means semi-resistant strains would more likely be killed before they are able to spread or develop resistance any further.

(archived WHO report)

  • $\begingroup$ The second source references a blog, which I would not consider a reliable source. However, I have read the actually text here, where the relevant page can be found in page 42 of the pdf. The book itself is quite well known, and its age is not disputed as far as I am aware. I had to post this link in the comments since I don't have enough internet points to include a third link in my post. $\endgroup$ – ning Apr 26 '17 at 21:23

Selection pressure (1, 2). One way or the other, there were few enough people taking the drug that it didn't really "matter" to P. falciparum (the deadliest of the malaria-causing parasites) on a population level until recently.

According to the 2014 paper Spread of Artemisinin Resistance in Plasmodium falciparum Malaria (3), the driver of Artemisinin resistance is a single point mutation (ie a change of a single DNA base pair) in a single gene. The thing to keep in mind is that these single nucleotide mutations happen all the time. You yourself most likely have 3 or 4 of them relative to your parent's genomes. Thus, this particular Artemisinin resistance mutation probably has occurred in the past.

However, as with most drug resistance mutations there is likely some fitness cost paid by the individual in which this mutation occurs. In environments without the drug, wild-type (ie non-mutant) parasites will outcompete the mutants, and the mutation will quickly disappear from the parasite population. It is only when the drug becomes commonplace that the mutant parasites gain the upper hand and the mutation spreads.

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  • $\begingroup$ Thank you for the answer, it seems a very likely hypothesis. I've given this some thought since as well, would it also be possible that artemisia annua (the 'herbal' form) contains additional active ingredients which also combat the parasite, such that the development of artemisinin resistance provides it no survival/selective advantage? I should clarify that I am suggesting this not as fact but as hypothesis-to-be-tested, since it is starting to sound a little alternative-natural-remedy-ish. $\endgroup$ – ning Apr 27 '17 at 8:54

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