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Artemisinin-based Combination Therapy (ACT)

Overview:

Successful malaria control depends greatly on treatment with efficacious anti-malarial drugs. Countries have a National Malaria Treatment Policy, that specifies drugs for treatment of both uncomplicated and severe malaria, malaria in pregnancy and what to do if first line treatment fails.

As drug resistance develops to existing drugs, new ones need to be introduced. For Plasmodium falciparum use of two or more drugs with different modes of action in combination is now recommended to provide adequate cure rate and delay development of resistance.

Currently artemisinin-based combination therapy (ACT) is recommended for  the treatment of P. falciparum malaria. Fast acting artemisinin-based compounds are combined with a drug from a different class. Companion drugs include lumefantrine, mefloquine, amodiaquine, sulfadoxine/pyrimethamine, piperaquine and chlorproguanil/dapsone. Artemisinin derivatives include dihydroartemisinin, artesunate and artemether. Implementation of the recommendation to use ACTs is limited by the small number of available and affordable co-formulated anti-malarial drugs, but most countries are now starting to implement this regimen. A co-formulated drug is one, in which two different drugs are combined in one tablet; this is important to ensure both drugs are used.

Artemether/lumefantrine (AL) was the first fixed-dose artemisinin-based combination therapy recommended and pre-qualified by WHO for the treatment of uncomplicated malaria caused by Plasmodium falciparum. It has been shown to be effective both in sub-Saharan Africa and in areas with multi-drug resistant P. falciparum in southeast Asia. It is currently recommended as first-line treatment for uncomplicated malaria in several countries. However, its complex treatment regimen of two doses daily for three days could affect adherence. A fixed-dose combination of amodiaquine-artesunate was launched in February 2007.

The benefits of ACTs are their high efficacy, fast action and the reduced likelihood of resistance developing. In order to make best use of them, it is critical to address issues of delivery, access and cost.

Chloroquine is still the first line treatment for P.vivax and P. ovale, while primaquine can be used to treat liver stage parasites of P.vivax, in areas of low transmission if adherence is guaranteed.

Key Points:

  • Drug resistance of P. falciparum to chloroquine and the antifolates has arisen throughout malaria endemic areas
  • Combination therapy is considered best for malaria management
  • Artemisinin-based compounds are used in combination with other classes of antimalarials to form ACTs
  • ACTs are highly effective and may help to delay development of resistance
  • It is important to ensure wide access to these drugs through effective delivery systems and affordable price
 

Programme Activities: 1) Drug Policy Change Project in Uganda; 2) AFFORD Health Marketing Initiative

After carrying out an evaluation of the availability of first and second line antimalarials at health facilities, the Malaria Consortium is now involved in developing and implementing commercial strategies for providing ACT in Uganda [AFFORD Project]. MC is also undertaking a comprehensive programme of activities to support the Uganda Ministry of Health to implement its new ACT policy.  This includes assessment of the impact of changing first-line treatment to ACTs and a field assessment of phasing in ACT to home based management. Drug Policy Change Project

 

References:

  1. * WHO (2006) Guidelines for the treatment of malaria. WHO/HTM/MAL/2006.1108. 
  2. * Garner, P., & Graves, P.M. (2005). The benefits of artemisinin combination therapy for malaria extend beyond the individual patient. PLoS Med 2(4): e105.
  3. * Bukirwa, H., Yeka, A., Kamya, M.R., Talisuna, A., Banek, K., Bakyaita, N., Rwakimari, J.B., Rosenthal, P.J., Wabwire-Mangen, F., Dorsey, G. & Staedke, S.G. (2006) Artemisinin Combination Therapies for Treatment of Uncomplicated Malaria in Uganda. PLoS Clin Trials 1(1): e7.
  4. * Wiseman V, Kim M, Mutabingwa TK, Whitty CJM (2006). Cost-effectiveness study of three antimalarial drug combinations in Tanzania. PLoS Med 3(10): e373.
  5. * Yeka A, Banek K, Bakyaita N, Staedke SG, Kamya MR, et al. (2005) Artemisinin versus nonartemisinin combination therapy for uncomplicated malaria: Randomized clinical trials from four sites in Uganda. PLoS Med 2(7): e190.
  6. * Shanks, G.D. (2006) Treatment of falciparum malaria in the age of drug resistance. Journal of Postgraduate Medicine 52 (4): 277-80.