Drug combination effective for treating uncomplicated malaria in children

The Four Artemisinin-Based Combinations (4ABC) Study Group. PLoS Med. 2011;doi:10.1371/journal.pmed.1001119.

Issue: December 2011

A new combination of antimalaria drugs is effective for treating children with uncomplicated malaria, according to results of a new study from Africa.

In a head-to-head comparison of the most currently available artemisinin-based combination therapies in sub-Saharan Africa, the results indicate that artemether-lumefantrine (AL; Coartem, Novartis), amodiaquine-artesunate (ASAQ) and dihydroartemisinin-piperaquine (DHAPQ) had efficacy up to day 63 post-treatment for the treatment of uncomplicated malaria in children aged 6 to 59 months.

Each site compared three of four artemisinin-based combination therapies: ASAQ, DHAPQ, AL or chlorproguanil-dapsone-artesunate (CD+A). The risk of recurrent infections was significantly lower for DHAPQ, followed by ASAQ and then AL. This finding supports the recent recommendation of considering DHAPQ as a valid option for the treatment of uncomplicated Plasmodium falciparum malaria, the researchers said.

From July 2007 to June 2009, a randomized, noninferiority (10% difference threshold in efficacy at day 28) clinical trial was conducted at 12 sites in seven sub-Saharan African countries. Overall, 4,116 children aged 6 to 59 months with uncomplicated P. falciparum malaria were treated (1,226 with AL; 1,002 with ASAQ; 413 with CD+A; and 1,475 with DHAPQ), actively followed up until day 28, and then passively followed up for the next 6 months, according to the study data.

At day 28, for the polymerase chain reaction-adjusted efficacy, noninferiority was established for three pair-wise comparisons: DHAPQ (97.3%) vs. AL (95.5%; OR=0.59; 95% CI, 0.37-0.94); DHAPQ (97.6%) vs. ASAQ (96.8%; OR=0.74; 95% CI, 0.41-1.34); and ASAQ (97.1%) vs. AL (94.4%; OR=0.50; 95% CI, 0.28-0.92).

For the polymerase chain reaction-unadjusted efficacy, AL was significantly less efficacious than DHAPQ and ASAQ, whereas DHAPQ had higher efficacy than ASAQ. However, noninferiority could not be excluded (OR=0.35, 95% CI, 0.26-0.48). CD+A was significantly less efficacious than the other three treatments, and results at day 63 were similar to those observed at day 28.

Disclosure: The project was funded by a grant of the European Developing Countries Clinical Trials Partnership. 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 program between DGCD and the Institute of Tropical Medicine, Antwerp, Belgium.

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