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Artemisinin & Malarial Treatments - Quick Facts

Artemisinin & malarial treatments  

Quick Facts:


The medicinal plant Artemisia annua is currently the sole source of artemisinin.

Artemisinin demand

The demand for artemisinin to combat malaria in the developing world is immense. Artemisinin Combination Therapies (ACTs) have now been adopted by 51 countries as first-line treatment in their national drug policies, and 24 are actually using ACTs. It has been estimated up to half a billion courses of artemisinin combination therapy (ACT) will be needed each year requiring around four hundred tons of artemisinin.

ACTs are more expensive than other anti-malarial drugs. For instance Coartem ™ costs $2.40 compared with $0.1 for a course of quinine.

Reducing the cost of artemisinin will reduce the cost of ACTs making them accessible to more people in countries where the annual health budget may be less than $4 per capita.

Artemisinin chemistry

Artemisinin is a sesquiterpene lactones derived from the Chinese medicinal plant, Artemisia annua. It contains an unusual trioxane ring which is thought to be responsible for its anti-malarial activity.

Artemisinin for clinical use is usually derivatised at the C12 position to modulate its stability and solubility. The most common derivatives are dihydro artemisinin, artemether, arteether, artesunate and artelinate.

Artemisinin anti-malarial activity
Artemisinin and its derivatives produce rapid clearance of parasitaemia and resolution of symptoms. They are active against all Plasmodium species, including Plasmodium falciparum and have an unusually broad activity, killing all stages of the parasite. Artemisinin and its derivatives are eliminated rapidly from the human body. They are safe and remarkably well tolerated.

The detailed mechanism by which Artemisinin and its derivatives kill the malarial parasite is the subject of much scientific debate and a consensus on its mode of action has yet to emerge.

Artemisinin combination therapies

The superiority of artemisinin combination therapies over monotherapies is well documented. The simultaneous use of two drugs with independent modes of action improves therapeutic efficacy and delays the development of resistance to the individual components of the combination.

The World Health Organization (WHO) is calling for pharmaceutical companies to stop marketing artemisinin monotherapies to prevent development of resistance to artemisinin.

Novartis offers Coartem ™ , which combines artemether and lumefantrine, at-cost for use in developing countries under an agreement with the World Health Organization. Coartem ™ is taken orally with fluids (preferably drinks containing fat, such as milk). A full treatment is a three-day course and the number of tablets per dose depends on body weight.

Alternative sources of artemisinin

Chemical synthesis of Artemisinin itself is not economically viable as
a means of production. However a new synthetic drug, known as Oz277 or RBx11160, which is based on the trioxane ring system of artemisinin is under development. It has now passed phase I and phase II clinical trials successfully as a monotherapy. The Indian manufacturer of generic dugs, Ranbaxy, is developing the drug in partnership with the not for profit public private partnership, Medicines for Malaria Venture (MMV), which is based in Geneva , Switzerland .

A second alternative, which is under development by a consortium led by the Institute for One World Health, is the manufacture of artemisinin through fermentation. This technology involves production of an artemisinin precursor, artemisinic acid, by a strain of yeast which harbours genes derived from A. annua. The scientists involved in this consortium reported successful laboratory-scale production of artemisinic acid by yeast earlier this year.

Both of these alternative sources of artemisinin are to be welcomed as part of the solution to artemisinin cost and security of supply. However
it has been estimated that, even if both of these technologies fulfill all their early promise, over fifty percent of artemisinin will have to be sourced from the plant
A. annua for the foreseeable future. Investment in development of high yield varieties of A. annua will reduce the cost of
artemisinin production significantly as well as securing supply.

Other applications of artemisinin

Artemisinin is showing promise as an anti-cancer compound in in vitro models. It has also been proposed as useful in treatment of schistosomiasis, another important parasitic disease of the tropics.


Sources

Report: ‘ Saving Time Buying Lives: Economics of Malaria Drugs in an Age of Resistance’ . This can be found at: http://www.nap.edu/catalog/11017.html

WHO guidelines for the treatment of malaria. This can be found at http://www.who.int/malaria/docs/TreatmentGuidelines2006.pdf

Meeting on the production of artemisinin and artemisinin-based combination therapies. The report from this meeting can be found on the WHO website www.who.int/malaria/docs/arusha-artemisinin-meeting.pdf


As Summarized by Centre for Novel Agricultural Products – Artemisia Projects  

http://www.york.ac.uk/org/cnap/artemisiaproject


World Map of Malaria Infected Areas