Malaria has been treated for over 350 years with quinine and quinine-derived drugs. However, in several areas of the world, some strains of the malarial parasite Plasmodium falciparum have developed resistance against these drugs. Recently, the World Health Organization (WHO) recommended the use of artemisinin-combination treatments (ACT) as the first-line treatment for multidrug-resistant falciparum malaria. The WHO estimates that current supplies of artemisinin are sufficient for only 30 million ACT, and is foreseeing the need for 130-220 million ACT in 2005 (WHO, 2004. Current research on the production of synthetic artemisinin-like compounds by the Roll Back Malaria project, pharmaceutical companies and academia resulted in a promising synthetic artemisinin-like compound (OZ277) which is currently undergoing phase I clinical trials. In about 5 years this drug is expected to be approved and made available to the public, however, meeting current global demands for ACT depends on the immediate availability of affordable artemisinin-derived drugs. This will involve expansion of the area under cultivation of Artemisia annua and improved methods of cultivation and processing of raw material, associated with more efficient methods for extraction and purification of artemisinin from plant material. This review addresses the agricultural, environmental and genetic aspects that may be useful in the successful large-scale cultivation of A. annua and for producing the antimalarial artemisinin in areas where it is urgently needed today. It also includes geographic aspects (latitude and altitude), which will help make decisions about crop establishment in tropical countries, and includes a list of Good Agricultural and Collection Practices for A. annua.
Artemisinin (qinghaosu) is extracted from the plant Artemisia annua (qinghao). Wild stands of these plants contain between 0.01 and 0.5% (w/w), with the highest concentrations in the leaves just before flowering. A review of recent agricultural techniques to improve yields from cultivated plants is presented.
Two field experiments were carried out in cool temperate maritime latitudes in NW Tasmania (41ºS) to assess whether wilting and drying Artemisia annua plants in the field after harvest had any detrimental effects on artemisinin (the source of important antimalarial drugs) or its precursor artemisinic acid. A third field experiment studied the effect of steam distillation of A. annua for its essential oil, prior to oven drying, on artemisinin and artemisinic acid. In the first two experiments whole plants were cut off at the base and left in situ for 1, 3 and 7 days (Experiment 1) and for 7, 14 and 21 days (Experiment 2). Experiment 2 included two additional treatments: (i) shade drying whole plants under ambient conditions in the field for 21 days and (ii) drying leaves, detached at harvest, for 21 days under ambient conditions inside in the dark. The effects of all of these treatments were compared with oven drying (35ºC) leaves which had been detached immediately after harvest. Field drying for 1, 3 or 7 days had no adverse effect on either artemisinin or artemisinic acid in Experiment 1 and all leaf concentrations were similar to oven drying. Field drying for 7 days in Experiment 2 also gave artemisinin and artemisinic acid levels similar to oven drying. However there was a trend for sunshade de-and dark drying for 21 days to give higher artemisinin than oven drying although artemisinic acid was unaffected. Distillation of A. annua plants for oil extraction, prior to oven drying at 35ºC, resulted in nil to negligible leaf concentration of artemisinin but artemisinic acid was unaffected. Field drying may be a way of reducing the cost of antimalarial drugs and the dual production of oil and artemisinic acid is a possibility.
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