assessed frequencies and levels of IgG antibodies to MSP-119 (8) and IgG1 and IgG3 antibodies to MSP-119, MSP-2, AMA-1, and glycosylphosphatidylinositol (32) across a wide gradient of ages and transmission intensities. both CSP and LSA-1, compared to 43.3% of individuals in the stable transmission area. In contrast, antibody levels to and frequencies of MSP-1 and EBA-175 were related in adults in areas of stable and unstable malaria transmission. Suboptimal immunity to malaria in areas of unstable malaria transmission may relate in part to infrequent high-level antibodies to preerythrocytic antigens and AMA-1. Areas of unstable low malaria transmission such as the highlands of East Africa are characterized by a persistent risk of medical malaria in older children and adults (13), whereas in areas with stable high-level transmission, the risk of medical malaria decreases markedly after the age of 3 to 5 5 years (30). Immunoglobulin G (IgG) antibodies to a number of vaccine candidate antigens including the preerythrocytic antigens circumsporozoite protein (CSP) (19), liver-stage antigen 1 (LSA-1) (19, 23), and thrombospondin-related adhesive protein (Capture) (29); the blood-stage antigen merozoite surface protein 1 (MSP-1) (5, 9, 26, 27); and the blood-stage and preerythrocytic antigen apical membrane antigen 1 (AMA-1) (24, 26) have been associated with safety from medical malaria in areas of stable transmission. The acquisition of IgG antibodies to these antigens also strongly correlates with increasing age (6, 12, 15, 25, 27, 29). However, the development of antimalarial antibodies in relation to age and safety from medical disease in areas of unstable transmission has not been well characterized. We have recently shown that in an part of Kenya with stable transmission, the presence of high-level IgG antibodies to three preerythrocytic Tamsulosin hydrochloride antigens, CSP, LSA-1, and Capture, correlates positively with safety from illness in adults (15) and from medical malaria in children (19). The association with safety from illness and disease was Tamsulosin hydrochloride attributable mainly to antibodies to CSP and LSA-1. We consequently hypothesize that one reason for the higher risk of medical malaria in older children and adults in areas of unstable transmission might be a relatively low rate of recurrence and/or level of IgG antibodies to CSP and LSA-1. To test this hypothesis, we measured IgG antibody frequencies and Tamsulosin hydrochloride levels of IgG antibody to CSP and LSA-1 in individuals aged 2 to 84 years with divergent malaria exposure in Kenya. In addition, we quantified and compared in the two populations of IgG antibodies to additional antigens under consideration as vaccine candidates, including the preerythrocytic-stage antigen Capture and blood-stage antigens erythrocyte binding antigen 175 (EBA-175), MSP-1, and AMA-1. MATERIALS AND METHODS Study human population and recruitment. Individuals 2 years of age and older were recruited from your sublocations of Kanyawegi (human population of 3,000) and Kipsamoite (human population of 3,500) in western Kenya. Kanyawegi is located in Kisumu District, a holoendemic lowland area with stable and intense malaria transmission, where entomological inoculation rates surpass 300 infectious bites per person per year (3). In contrast, Kipsamoite in Nandi Area is located in an epidemic-prone highland area characterized by unstable malaria transmission during the continuous interepidemic periods (10), with an estimated entomological inoculation rate of <1 infectious bite per person per year (C. C. John, unpublished data). This cross-sectional study was carried out in August 2001 at a time of relatively high malaria incidence in the highland area (14) and stable malaria incidence in Nkx1-2 the lowland area. Blood was collected by venipuncture from adults (10 to 20 ml) and children (5 ml). Microscopy was performed to determine blood-stage illness, as previously explained (16). Individuals were recruited through local barasas or meetings across the study sites, where information about the study was offered. Individuals who experienced attended the barasa or discussed the study with field assistants were eligible to join the study. Field assistants had been asked to sign up.