ARTEMISININ DERIVATIVES
The increasingly widespread presence of drug-resistant P. falciparum has allowed malaria to spread to new areas and to re-emerge in areas where it had previously been eliminated. The increase in malaria cases and this re-emergence has prompted the need for the development of new antimalarial treatments. A new class of antimalarials - the artemisinin-derived compounds, were first isolated and developed in China in the 1980s. Artemisinin is extracted from a traditional Chinese medicinal plant, Artemesia annua or sweet wormwood, and can then be chemically converted into several derivatives.

History of Artemisinin

The world is greatly indebted to Chinese scientists and traditional healers for their discovery and open sharing of the antimalarial properties of A. annua. In China, where A. annua was first described, it is known as qinghao, and the active ingredient artemisinin is termed qinghaosu. Chinese healers have used A. annua for the treatment of malaria and other maladies since at least the second century BCE.¹ In 1967 Mao Tse-Tung’s government ordered a systematic examination of the traditional Chinese herbal pharmacopoeia that led to the isolation of the compound qinghaosu, or Artemisinin in 1972.

Historical Documentaion: A.annua was first mentioned for its medicinal virtues by the famous Chinese herbalist Li Shizhen in 1596.

Current Source

Artemisinin is currently extracted from dried leaves and inflorescences from A. annua, an annual herb that grows wild throughout China and Southeast Asia. The plants - and the many farmers who grow them - are responsible for saving the lives of countless numbers of people who are treated with ACTs each year. The farmers are currently the sole source of artemisinin worldwide, and have worked closely with individual governments and pharmaceutical companies to ensure that enough artemisinin is available.
A. annua is grown primarily in China, but is also grown in Africa and other areas of Asia. Novartis, whose antimalarial Coartem^TM is currently the only artemisinin combination therapy (ACT) that is pre-approved by the World Health Organization (WHO), has worked extensively with these farmers, particularly in Africa, to increase current production levels and plant new crops of A. annua. A. annua was first planted in East Africa in 1994, and plans are underway to scale up cultivation and establish more extractive facilities in the region.

Pharmaceutics: Artemisinin Combination Therapies

Artemisinin-derived molecules such as artesunate, arteether, artemether, or dihydro-artemisinin (DHA) are extremely potent antimalarials that act rapidly against the parasite's asexual erythrocytic (red blood cell) stage. Notably, these compounds also have a strong activity against the parasite blood-stage gametocytes (sexual stage), which can potentially help to reduce the rate of malaria transmission. Artemisinin-derived drugs have been shown to be highly efficacious against parasites resistant to first-line antimalarial drugs. For these reasons, artemisinin-derived molecules are being used in recently developed artemisinin combination therapies (ACTs).

Artemisinin combination therapies (ACTs) mix fast-acting and rapidly-cleared artemisinin-derived drugs with other antimalarials with longer half-lives such as lumefantrine (as in Coartem^tm) or mefloquine (as in Artequin^tm). These combination products are recommended over monotherapies (single drugs) because they help to prevent the development of resistant parasites. ACTs have been used in Southeast Asia, Africa, and other parts of the world and it is believed that they may slow the spread of drug resistance and reduce the overall malaria transmission rates. Unfortunately, due to their high cost, these therapies are not widely accessible to the people who most need them.

The World Health Organization (WHO) and other development agencies first endorsed artemisinin-based therapies for the treatment of malaria in 2004. The WHO 2005 recommendations for first-line malaria treatment include several ACTs - in fact, all six recommended therapies include artemisinin derivatives. In 2006, the WHO requested the discontinuation of manufacturing and marketing of all artemisinin monotherapies, except for the treatment of severe malaria, in an effort to prevent the development of parasites resistant to artemisinins.