For over 1,500 years, Chinese herbalists have used leaves from the Artemisia annua shrub (sweet wormwood) to treat malaria. Only in the late 1960s was its anti-malarial ingredient, artemisinin, identified and extracted. Today, artemisinin is considered the treatment of choice for uncomplicated falciparum malaria, as prescribed by the World Health Organization (WHO) in 2001.
Artemisia annua grows in temperate regions and in tropical areas at higher altitudes. As a treatment for malaria, it has been traditionally grown in Asia, predominantly China and Vietnam, where it was originally harvested from the wild. Due to the rapid increase in demand and the relatively low dry-leaf and artemisinin yield from wild varieties, most Artemisia annua is now commercially grown on small holdings and larger plantations. This has resulted in the development of new high-yielding varieties, producing between one and four tonnes per hectare of dry leaf with up to 1.2% artemisinin content.
Commercial cultivation of Artemisia annua has now spread to other parts of Asia, including India, as well as Africa, especially East Africa. Production ‘trials’ of the plant and seed development are also being conducted in Europe, Australia, and Brazil.
The extraction of artemisinin from the plant has traditionally used N-Hexane, a cost-effective solvent. However, N-Hexane is poisonous and flammable, raising potential safety and environmental concerns. This has led to the search for new, safer solvents to enable the extraction of artemisinin, including supercritical CO2, Ethanol, HFCs (hydrofluorocarbons) and Ionic Liquids.
Following its extraction and purification from the plant, artemisinin is processed synthetically under GMP guidelines (good manufacturing practice) into a range of derivatives, including dihydroartemisinin (DHA), artesunate, arteether, and artemether. It is in one of these forms that it is combined with other suitable anti-malarials e.g., amodiaquine, piperaquine etc, to produce ACTs (artemisinin-based combination therapies).
In early 2006, due to global concerns about the need to safeguard the efficacy of this antimalarial, WHO urged the malaria community to stop the production and use of artemisinin monotherapies and switch to ACTs.