There is evidence from several studies that in areas where the transmission of malaria is seasonal, the use of IPT can reduce substantially the incidence of clinical malaria in children under the age of five years, by as much as 90% (Greenwood et al, Trends in Parasitology 24(11):485-6, 2008). The most effective regimen is SP+AQ but alternative regimens are needed because amodiaquine can be poorly tolerated (Sokhna et al PlosOne 3:e1471, 2008) and resistance to SP is increasing. In recent trials in Senegal and The Gambia, PQ combined with DHA or SP was as effective against malaria, and better tolerated, than SP+AQ. Of these regimens, only DHA+PQ is licensed for use as an antimalarial in African countries. However there are no data on pharmacokinetics of PQ when used for IPT in children, and the impact of DHA+PQ in preventing spread of resistance is not known. This trial aims to provide this information in order to evaluate the suitability of DHA+PQ for use for seasonal IPT in children and to determine the optimum dose regimen for piperaquine.