A recent trial on AQ in older patients from western Burkina Faso demonstrated a PCR-corrected ACPR rate of only 82% after 28 days of follow-up. Similarily, data from 117 children aged five years or less and treated in Nouna town in 2005 with AQ PF-04217903 showed an ACPR rate after PCR-based correction for recrudescence at day 28 of only 61%. Finally, preliminary results on the high efficacy of MB monotherapy in semi-immune adults with falciparum malaria provide further evidence for a substantial contribution of MB to the efficacy of MB-based combination therapies. At 82% ACPR, the standard regime AS-AQ surprisingly did worse than expected and than it has been reported previously from other places in West Africa. It is currently not clear if this finding reflects local differences in AQ resistance, a real inferiority of AS-AQ compared to MB-AQ, or both. Although the AQ used for this study was taken from a local source, we are confident that it is of good quality. Drugs from the essential drug store of the Ministry of Health are regularly quality controlled and a recent study on the quality of malaria drugs in the Nouna Health District provided no evidence for quality problems with AQ. Secondly, although performing rather poor in terms of overall efficacy, MB-AS achieved a more rapid clearance of P. falciparum parasites than the other two treatment regimes. This provides evidence in humans for a clinically relevant synergy between an artemisinin derivative and MB, which has already been shown in vitro. Adding MB to ACT may thus be an option to further speed up the rapid parasite clearance Evofosfamide conferred by the artemisinin derivatives. Likely related to the short elimination half-life of both MB and AS, re-infections were more common in children treated with this combination than in patients receiving treatment containing AQ. Also, rapid parasite clearance in MB-AS may interfere with the development of sustained immune mechanisms preventing re-infections. Similar findings have been observed in northern Ghana where the fastest regimen in parasite clearance, SP-AS, produced the highest proportion of re-infections. As MB is both available and affordable, the combination MBAQ would be an interesting alternative antimalarial regimen when shown to be safe and effective in larger multi-centre phase III studies. Such studies are now planned for in the frame of a publicprivate- partnership by our group. Apart from the potential benefit of another effective antimalarial regimen contributing to a healthy competition of different regimens on the market, MB can be considered a re-emerging antimalarial with the potential to be a valuable partner drug in various ACT and non-artemisinin drug combinations. In conclusion, MB-AQ is a promising alternative drug combination against falciparum malaria in SSA. Moreover, MB has the potential to further accelerate parasite clearance when used in ACT.