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Artemisinin-based combination therapies: a vital tool in efforts to eliminate malaria.

ABSTRACT: Plasmodium falciparum resistance to chloroquine and sulphadoxine-pyrimethamine has led to the recent adoption of artemisinin-based combination therapies (ACTs) as the first line of treatment against malaria. ACTs comprise semisynthetic artemisinin derivatives paired with distinct chemical classes of longer acting drugs. These artemisinins are exceptionally potent against the pathogenic asexual blood stages of Plasmodium parasites and also act on the transmissible sexual stages. These combinations increase the rates of clinical and parasitological cures and decrease the selection pressure for the emergence of antimalarial resistance. This Review article discusses our current knowledge about the mode of action of ACTs, their pharmacological properties and the proposed mechanisms of drug resistance.

SUBMITTER: Eastman RT

PROVIDER: S-EPMC2901398 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature

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Artemisinin-based combination therapies: a vital tool in efforts to eliminate malaria.

Eastman Richard T RT Fidock David A DA

Nature reviews. Microbiology 20091102 12

Plasmodium falciparum resistance to chloroquine and sulphadoxine-pyrimethamine has led to the recent adoption of artemisinin-based combination therapies (ACTs) as the first line of treatment against malaria. ACTs comprise semisynthetic artemisinin derivatives paired with distinct chemical classes of longer acting drugs. These artemisinins are exceptionally potent against the pathogenic asexual blood stages of Plasmodium parasites and also act on the transmissible sexual stages. These combination ...[more]

PMID: 19881520

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Project description:OBJECTIVES:To compare the efficacy and safety of artemisinin combination therapies for the treatment of uncomplicated falciparum malaria in Uganda. DESIGN:Randomized single-blind controlled trial. SETTING:Tororo, Uganda, an area of high-level malaria transmission. PARTICIPANTS:Children aged one to ten years with confirmed uncomplicated P. falciparum malaria. INTERVENTIONS:Amodiaquine + artesunate or artemether-lumefantrine. OUTCOME MEASURES:Risks of recurrent symptomatic malaria and recurrent parasitemia at 28 days, unadjusted and adjusted by genotyping to distinguish recrudescences and new infections. RESULTS:Of 408 participants enrolled, 403 with unadjusted efficacy outcomes were included in the per-protocol analysis. Both treatment regimens were highly efficacious; no recrudescences occurred in patients treated with amodiaquine + artesunate, and only two occurred in those treated with artemether-lumefantrine. However, recurrent malaria due to new infections was common. The unadjusted risk of recurrent symptomatic malaria was significantly lower for participants treated with artemether-lumefantrine than for those treated with amodiaquine + artesunate (27% versus 42%, risk difference 15%, 95% CI 5.9%-24.2%). Similar results were seen for the risk of recurrent parasitemia (51% artemether-lumefantrine versus 66% amodiaquine + artesunate, risk difference 16%, 95% CI 6.2%-25.2%). Amodiaquine + artesunate and artemether-lumefantrine were both well-tolerated. Serious adverse events were uncommon with both regimens. CONCLUSIONS:Amodiaquine + artesunate and artemether-lumefantrine were both highly efficacious for treatment of uncomplicated malaria. However, in this holoendemic area, despite the excellent performance of both regimens in terms of efficacy, many patients experienced recurrent parasitemia due to new infections. Artemether-lumefantrine was superior to amodiaquine + artesunate for prevention of new infections. To maximize the benefit of artemisinin combination therapy in Africa, treatment should be integrated with strategies to prevent malaria transmission. The impact of frequent repeated therapy on the efficacy, safety, and cost-effectiveness of new artemisinin regimens should be further investigated.

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Artemisinin-based combination therapies: a vital tool in efforts to eliminate malaria.

Publications

Artemisinin-based combination therapies: a vital tool in efforts to eliminate malaria.

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