A large study from Africa, published in this week's PLoS Medicine, has found that in a direct comparison, three types of new, fast-acting antimalarial artemisinin-based combination therapy drugs (ACTs), which comprise artemisinin derivatives in combination with a partner antimalarial drug, AL (artesunate–mefloquine), ASAQ (artesunate–amodiaquine) and DHAPQ (dihydroartemisinin–piperaquine) are all effective for treating children with uncomplicated malaria.
In a randomized trial from 12 sites in 7 sub-Saharan African countries involving 4,116 children aged under 5 years, The Four Artemisinin-Based Combinations (4ABC) Study Group found that AL, ASAQ, and DHAPQ were all extremely effective in getting rid of the Plasmodium falciparum parasite responsible for causing malaria for up to 63 days after treatment. Another ACT called CD+A (chlorproguanil plus artesunate) was withdrawn partway through the trial because of side-effects but the study findings also suggest that this drug was less efficacious than the other ACTs.
Importantly, the research group also found that the risk of children becoming re-infected with malaria parasites soon after treatment was lowest for DHAPQ followed by ASAQ and then AL. Furthermore, because of the large size of the study these findings are likely to be generalizable to other African countries and will inform national antimalarial drug policies throughout the region.
AL and ASAQ are already included in the antimalarial drug policies of many sub-Saharan African countries but the research group state that their findings support the WHO recommendation that DHAPQ should also be considered for the treatment of uncomplicated P. falciparum malaria.
The researchers say: "This study confirms that DHAPQ is a valid third option for the treatment of uncomplicated P. falciparum malaria, as its efficacy is excellent and comparable to the other ACTs, while its long post-treatment prophylaxis could be an additional advantage."
Funding: This project was funded by a grant of the European Developing Countries Clinical Trials Partnership (EDCTP). The Medicine for Malaria Venture (MMV) provided additional funding mainly used for the genotyping of blood samples. The Belgian Directorate-General for Development Cooperation (DGDC) provided support through the framework agreement programme between DGCD and the Institute of Tropical Medicine, Antwerp, Belgium. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing Interests: Prof. Umberto d'Alessandro has received research funding from Sigma Tau and Sanofi-Aventis. Dr. Quique Bassat has received in the past three years speaker fees and travel grants from Sigma Tau SP, Pomezia, Rome, Italy. All other authors declare no competing interests.
Citation: The Four Artemisinin-Based Combinations (4ABC) Study Group (2011) A Head-to-Head Comparison of Four Artemisinin-Based Combinations for Treating Uncomplicated Malaria in African Children: A Randomized Trial. PLoS Med 8(11): e1001119. doi:10.1371/journal.pmed.1001119
CONTACT:
Umberto D'Alessandro
Prince Leopold Institute of Tropical Medicine
Parasitology Department
Nationalestraat 155
Antwerp, B-2000
Belgium
udalessandro@itg.be or udalessandro@mrc.gm
Journal
PLoS Medicine