Artemisinin combination therapies (ACT) are currently recommended by the World Health Organization (WHO) as the best available treatment for malaria caused by Plasmodium falciparum infection. As of 2010, artemisinin and its synthetic derivatives, artesunate, artemether and dihydroartemisinin, are the "newest" anti-malarial drugs to be recommended for global use. In 2006, according to Roll Back Malaria, recommended artemisinin combinations included artemether with lumefantrine, artesunate plus amodiaquine, artesunate plus mefloquine and artesunate plus sulfadoxine-pyrimethamine, in different malaria endemic areas, depending on the efficiency of anti-malaria drugs in those regions. Today, the Malaria Consortium also includes companion drugs piperaquine and chlorproguanil/dapsone, and combinations are being co-formulated into single dose tablets to increase adherence to treatment and reduce the risk of parasites developing drug resistance. Use of artemisinin drugs alone is not recommended for malaria treatment.
History
Leaves from Artemisinia annua, or the sweet wormwood plant, have been used by Chinese herbalists in tisanes for nearly 2,000 years as an anti-malarial treatment. In the 1970s the active ingredient, artemisinin, was extracted and proven to have anti-malarial properties. Artemisinin drugs are also known to have some effectiveness as anti-cancer treatments.
Impact of Malaria
Historically, malaria has occurred in most countries of the world, but today the disease is endemic in countries in the southern hemisphere. The disease is caused by infection with Plasmodium parasite species, malaria parasites being transmitted to humans via the bite of the female Anopheles mosquito. Plasmodium falciparum is the species that causes the vast majority of malaria deaths. One half of the world's population is at risk of malaria; the disease causes almost a million deaths each year, mostly in children under five years of age, and 247 million new infections, according to 2008 data from Roll Back Malaria and the Global Malaria Action Plan.
Drug Resistance
Like other infectious agents, malaria parasites can develop resistance to treatments; resistance can be hastened when drugs are used inappropriately. Combination treatments are strongly recommended because malaria parasites have already developed widespread resistance to two other anti-malarial drugs, chloroquine and sulphadoxine-pyrimethamine (S/P). However, these drugs are still useful; both S/P and chloroquine are recommended to treat malaria in certain situations. It is hoped that by using ACTs, widespread resistance to artemisinins can be averted.
Avoiding Drug Resistance
The Malaria Consortium advocates that the use of ACTs is proven to reduce the risk and spread of drug resistance in malaria parasites. In particular, by using drugs which have different modes of action, development and spread of drug resistance can be limited. For example, artemisinins are fast-acting drugs, and S/P is slow acting; using this combination of fast- and slow-acting drugs reduces the opportunity for the parasite to develop drug resistance to either drug.
Reducing Drug Resistance Spread
Unfortunately, according to Dondorp et al., 2010, writing in the journal "Nature," resistance to artemisinins has been confirmed in P. falciparum parasites around the Thai-Cambodia border area. One factor which may have allowed the development of drug resistant parasites is the unregulated use of artesunate as a single therapy. However, there is hope and evidence that the spread of resistance to artemisinins can be slowed and even reduced by the use of ACTs. In order to limit any further spread of artemisinin resistant malaria parasites, prompt and effective anti-malarial treatment with ACTs for malaria illness with parasite diagnoses is crucial.
