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| Antimalarial Compounds in Artemisia Annua |
Answered by: Conrad Richter
Question from: Beth Dorsey
Posted on: April 25, 2004
Thanks for your time in considering this question. I am trying to understand modern medical use of Artemisia annua for malaria. I know that several different compounds in Artemisia annua are used in different ways to treat or prevent malaria, among them artemisinin, artemether, artesunate; but I don’t understand which are used when and how. I’ve heard that at least one or some of them are used most in conjunction with other malaria drugs. I also am wondering if the malaria bug cannot become resistant to artemisia compounds, or if it is just as able to become resistant to it as to any other malaria drug.
Artemisinin is the compound that is extracted from the chinese herb, qingguo, also known in english as sweet wormwood or sweet annie and known botanically as Artemisia annua. Artemether and artesunate are closely related derivatives of artemisinin that are manufactured from artemisinin. Artesunate is more water soluable while artemether is more lipid or fat soluble. In the body, both artemether and artesunate are converted to dihydroartemisinin which is the highly active metabolite that kills the malaria parasite. Artemisinin is also converted to dihydroartemisinin but artemisinin is poorly soluble in both water and lipids and thus does not get transported effectively in the body to the where the parasites are.
Provided that the recommended dosage regimen is followed, both artesunate and artemether are similarly effective against the malarial parasite. A study to compare the bioavailability and antimalarial activity of artesunate and artemether (http://www.blackwell-synergy.com/links/doi/10.1046/j.1365-2125.2001.01458.x/full/) showed that dihydroartemisinin levels were higher when artesunate was taken. It is known that there is a threshold which the dihydroartemisinin levels must exceed before the malarial parasite begins to succumb, so artesunate appears to be more effective. However, with the proper dosage regimen artemether can produce levels above the threshold that last a little longer than artesunate. And as patients regain their appetite for food, the body’s ability to absorb artemether increases also, so artemether’s effectiveness increases slightly over time.
Artemisinin derivatives are only useful for the treatment of malaria; they are not recommended for the prevention of malaria. I am not sure why this is so, but it may have something to do with how quickly the derivatives and their metabolites are execreted from the body. There are few if any side effects of artemisinin-derivative therapy, so side effects don’t seem to be a reason for not using artemisinin derivatives as a preventative. Perhaps concerns about possible resistance are the reason.
Combination treatments using artemisinin derivatives with other drugs have been found to give a longer lasting protection against malaria. When used alone, artemisinin derivatives quickly clear the body of the malarial parasites, but they provide no protection against reinfection. The combination of artesunate with the common antimalarial drug mefloquine, for example, cures malaria and keeps patients free for over two months, according to a study in Thailand where multi-drug resistant malaria is prevalent (http://aac.asm.org/cgi/content/full/42/1/135?view=full&pmid=9449273).
Presumably then (and you need to conform this with your doctor) if you are not likely to be reexposed to malaria-infected mosquitoes, then artemisinin derivatives taken alone will work fine. But if you are in an area where reinfection is a problem, then you may want to consider one of the artemisinin-drug combination treatments.
Because artemisinin derivatives have strong activity against the parasite that causes schistosomiasis, they are being used alone or in comination with other drugs to treat that debilitating disease also (http://www.who.int/tdr/publications/tdrnews/news62/artemether.htm). Because artemisinin derivatives are effective against both malaria and schistosomiasis, two of the world’s most debiliting parasitic diseases, there is a real concern that widespread use of artemisinin derivatives could eventually lead to the development of artemisinin-resistant forms of malaria and schistosomiasis. In fact, the use of artemisinin derivatives against schistosomiasis is only recommended where malaria is not a problem.
No clinical reports of resistance to artemisinin derivatives have yet emerged. But experience suggests that when any herb or drug is used repeatedly to kill a pathogen, resistance will eventually develop, and resistance is expected to develop soon. A laboratory study has shown that resistance can be induced in the malaria parasite (http://aac.asm.org/cgi/content/full/44/2/344).