Malaria is one of the most common infectious diseases in the world and 40% of the world population is exposed to malaria. Despite the current control strategies such as rapid diagnosis and treatment of disease cases, use of insecticide impregnated materials and indoor residuals spraying with insecticides, malaria remained a main cause of morbidity and mortality particularly in sub Saharan Africa. More than 90% of the deaths due to malaria occurred in this region and 88% of these deaths occurred in children aged less than 5 years of age. In absence of vaccine that can be used in public health, there is an urgent need for a simple and efficient control strategy. Malaria intermittent preventive treatment (IPT) defined as the administration of curative dose of anti-malarial drug at predefined time intervals, appears as one of the most promising strategies. Given through the Expanded Program of Immunization (EPI), the strategy reduced the incidence of malaria by 30%. More drastic reductions were obtained in children aged 0-5 years and even 0-10 years when the malaria transmission season was targeted for the administration of the strategy. Our research work in Mali has assessed the following:- The impact of implementation of IPT administrated through EPI (IPTi) on: i) the resistance of P. falciparum to Sulfadoxine pyrimethamine (SP); ii) EPI vaccine coverage, and iii) mortality of children of 4-18 months of age. - The efficacy of IPT in children targeting the malaria transmission season (IPTe) in a context of low and high coverage of insecticide impregnated nets (ITN).We have found that the implementation of IPTi at the district level has resulted in an augmentation of the EPI vaccine coverage. The EPI vaccine coverage was 53% in the non-intervention zone compared to 69.5% in the intervention zone (p<0,01). There was a reduction in all cause mortality of 27% (RR= 0.73, 95% CI : 0.55-0.97, p=0.029) in children aged 4-18 months. The frequencies of molecular markers of the resistance of P. falciparum to SP were similar at the beginning and the end of the one year implementation period and between the intervention and non-intervention zones.Two doses of SP given at 8 weeks interval during the transmission season, reduced the incidence of malaria episodes during the transmission season by 69.4% in children aged less than 5 years and by 63.4% in children aged 5-10 years in a context of very low ITN use (<5%). In another study that we have conducted, IPT with SP + Amodiaquine (AQ) given at three occasions at one month interval during the transmission season reduced the incidence rate of clinical malaria by 82% (95% CI: 78%– 85%; P<0.001), and the incidence of severe and complicated malaria by 87% (95% IC 42% – 99%, P=0.001) in children aged 3 to 59 months of age despite an ITN use of greater than 99%.There was no serious adverse event related to the use of SP or SP+AQ in IPT during the two studies. Our results support the recommendation of IPT targeting the transmission season and IPT given through the EPI for malaria control in children.