Artemisinin derivatives and malaria: useful, in combination with other antimalarials.

(1) Plasmodium falciparum malaria can be fatal, especially in young children and non-immune persons. Several drugs are effective but emergence of parasite resistance limits the choice in various parts of the world. Resistance to mefloquine and even to quinine has been reported in Southeast Asia; (2) What is the role of artemisinin derivatives (mainly artesunate and artemether) in the treatment of uncomplicated P. falciparum malaria? To answer this question we conducted a review of the literature, based on Prescrire's standard methodology; (3) Trials of single-agent therapy with artemisinin derivatives showed rapid clinical and parasitological effects, but relapses were frequent during the weeks following treatment. Artemisinin derivatives are therefore used in combination with other antimalarials; (4) In 2006, no parasite resistance to artemisinin derivatives has been detected in Southeast Asia after about 10 years of use; (5) In Southeast Asia, parasitological failure at 28 days was less frequent after treatment with artesunate (for 3 days) plus mefloquine than with mefloquine alone. The artemether + lumefantrine combination has similar efficacy to the artesunate + mefloquine combination. In Africa, several trials have shown that combinations based on artemisinin derivatives are more consistently effective than combinations not including artemisinin derivatives. In regions with high-level resistance to amodiaquine, one trial showed that artemether + lumefantrine was more effective than artesunate + amodiaquine; (6) The main adverse effects of artemisinin derivatives are gastrointestinal and neurological disorders, but less are rarely severe. Combinations based on artemisinin derivatives have different adverse effects, depending on the drugs used; (7) Artesunate is the artemisinin derivative most widely studied in pregnant women: in a series of more than 400 pregnancies, abnormalities were no more frequent than in the general population; (8) In practice, in regions where P. falciparum malaria is endemic, early combination therapy based on artemisinin derivatives is often recommended. For uncomplicated malaria in travellers, combination therapy based on artemisinin derivatives is one option, along with atovaquone + proguanil, quinine (less convenient) and mefloquine (frequent neuropsychological effects).