Malaria caused by Plasmodium falciparum continues to be a global problem with devastating consequences. A greater understanding of the immunologic and parasitologic factors associated with infection and disease is badly needed, and will accelerate the development of highly protective vaccines for both mothers and children. Pregnancy malaria is associated with low birth weight, maternal anemia, and gestational hypertension, and both inflammation and the fetal response to infection may contribute to these poor outcomes. Childhood malaria is a major cause of mortality, and we have found that risk of childhood malaria is related to in utero exposure to pregnancy malaria, as well as other host factors like iron status and constitutive cytokine levels. Pregnancy malaria is caused by a distinct parasite binding phenotype, and as our primary hypothesis in this study we speculate that severe childhood malaria parasites may also have distinct features. A longitudinal cohort study will be conducted in Ouelessebougou, Mali an area of intense seasonal transmission. Up to 2000 pregnant women and their infants and 2000 children ages 0 - 3 will be enrolled and followed to age 5 years, with clinical evaluation and periodic venous and peripheral blood samples obtained. In addition, 2000 febrile children up to age 10 years will be enrolled at the Ouelessebougou district health centers or the Gabriel Toure Pediatric Hospital in Bamako, Mali, with acute and convalescent samples being obtained and 500 pregnant women enrolled at the health centers and hospital in Ouelessebougou district or the Gabriel Toure Hospital in Bamako for a case-control study on pregnancy malaria and preeclampsia. Clinical, parasitologic and host response (including immunologic) endpoints will be analyzed using appropriate statistical methods, including possible confounders, to determine factors associated with infection and disease in pregnant woman and young children....