Artemisinin-based combination therapies

Three currently-used artemisinin based combination therapies (ACT) artesunate-mefloquine, artemether-lumefantrine and dihydroartemisinin-piperaquine, have been proven highly simple, safe and effective in the treatment of multidrug resistant P. falciparum malaria. 

Chloroquine is the drug of choice in the treatment of nonfalciparum and sensitive falciparum malaria. It rapidly terminates fever (in 24-48 hours) and clears parasitemia (in 48-72 hours) caused by sensitive parasites. It is still used to treat falciparum malaria in some areas with widespread resistance, in particular much of Africa, owing to its safety, low cost, antipyretic properties, and partial activity, but continued use of chloroquine for this purpose is discouraged, especially in nonimmune individuals. Chloroquine has been replaced by other drugs, principally artemisinin-based combination therapies, as the standard therapy to treat falciparum malaria in most endemic countries. Chloroquine does not eliminate dormant liver forms of P vivax and P ovale, and for that reason primaquine must be added for the radical cure of these species. 

The relative efficacy and safety of artemisinin-based combination therapies are now under active investigation. In general, the leading regimens are highly efficacious, safe, and well tolerated, and they are the new standard of care for the treatment of uncomplicated falciparum malaria. 

Davis TM, Karunajeewa HA, Ilett KF. Artemisinin-based combination therapies for uncomplicated malaria. MedJAust. 2005 182 181-185. 

Artemisinin, the principal bioactive antimalarial compound and its derivatives from Artemisia annua, a Traditional Chinese Medicinal plant used against fevers and malaria, have yielded a potent new class of antimalarials. The anti-malarials derived from A. annua are considered an integral part of the solution where malaria has become resistant to other medicines and even in areas where resistance is not yet a problem (S). Artemisinin-based combination therapies (ACTs) have been recommended in the countries where falciparam malaria - the most resistant form of the disease- is endemic (9). While ACTs for all would be the ideal strategy, it is most impractical for poor and remote communities, politically unstable areas, and people who dislike the use of modem medicine (10). 

Douglas and coworkers [171] have strongly recommended artemisinin-based combination therapies to eliminate malaria, which is used to treat P. falciparum malaria even when most blood-stage infections caused by Plasmodium vivax still respond to chloroquine treatment, a chloroquine-resistant P. vivax strain has been already detected, suggesting that artemisinin-based combination therapies should be used to treat both parasite strains. 

While experimental resistance to artemisinin had been induced earlier, blood samples from Cambodia, Senegal and French Guiana provided in 2005 the first hints on drug-resistant Plasmodium falciparum isolates in the field. [483] The first clinical cases were reported in 2008 from PaUin and other provinces in western Cambodia [484], and in 2012, resistant strains were also found in neighbouring Thailand. [485] In these coimtries, artemisinin and its derivatives had been frequently used as mono-therapy and in an imcontroUed fashion. While there is an enormous effort under way to elucidate the mechanisms of resistance development, the WHO urges to only apply artemisinin-based combination therapy (ACT) for the treatment of malaria in order to secure and maintain the efficacy of our most recent - and at the same time oldest - weapon in the combat of this devastating disease for as long as possible. [486]... 

Artemisinin-based combination therapies are now the treatment of choice for malaria in several endemic countries. However, knowledge about the safety of artemisinin compounds in combination with other anti-malarial drugs is still developing. 

Acrylic acid (ACR), 2884, 2906 ACT. See Artemisinin-based combination therapy (ACT)... 

Artemisinin, a sesquiterpene lactone endoperoxide and isolated from aerial parts of Artemisia annua L. plants (family Asteraceae commonly known as sweet wormwood), is popular as a potent, promising, highly effective, safe, and best therapeutic agent against drug-resistant strains of Plasmodium sp. The low yield of artemisinin content, is a serious limitation to its ability and affordablity to the most malaria sufferers. The chemically synthesized artemisinin is also costly due to low yield of the process. The World Health Organization (WHO) recommends the use of artemisinin-based combination therapies (ACTs), for the first-line treatment of malaria. To date, A. annua L. 

Cohen J, Singh I, O Brien M (2008) Predicting global fund grant disbursements for procurement of artemisinin-based combination therapies. Malar J 7 200... 

Facts on acts (Artemisinin-based combination therapies). Further information available at http // www.searo.who.int/LinkFiles/Drug Policy RBMInfosheet 9.pdf (accessed November 2007)... 

In many malaria endemic countries, artemisinin-based combination therapies (ACTs) are now established as standard treatment regimens for falciparum malaria, the most lethal form of malaria which still causes more than one million deaths annually throughout the world. However, recent reports of parasite resistance to artemisinins in four countries of the Greater Mekong subregion, Cambodia, Myanmar, Thailand and Vietnam underlie the importance of continuous surveillance of therapeutic efficacy of ACTs as a tool of national malarial drug policies [1 ]. 

German PI, Aweeka FT. Clinical pharmacology of artemisinin-based combination therapies. Clin Pharmacokinet 2008 47(2) 91-102. 

---