Antibodies to Pre-erythrocytic Plasmodium falciparum Antigens and Risk of Clinical Malaria

Background. IgG antibodies to pre-erythrocytic antigens are involved in prevention of infection and disease in animal models of malaria but have not been associated with protection against disease in human malaria. Methods. Levels of IgG antibodies to circumsporozoite protein (CSP), liver-stage antigen type 1 (LSA-1), and thrombospondin-related adhesive protein (TRAP) were measured in 86 children in a malaria-holoendemic area of Kenya. The children were then monitored for episodes of clinical malaria for 52 weeks. Results. Children with high levels of IgG antibodies to CSP, LSA-1, and TRAP had a decreased risk of clinical malaria (adjusted hazard ratio, 0.29; 95 % confidence interval 0.10–0.81; P .02), a lower incidence of clinical malaria (P .006), protection from clinical malaria with a parasite level of 4000 parasites/L (P .03), and a higher hemoglobin level at enrollment (P .009), compared with children with lower antibody levels. Protection against malaria morbidity was associated primarily with antibodies to CSP and LSA-1. Conclusions. Kenyan childrenwith high levels of IgG antibodies to the pre-erythrocytic antigensCSP, LSA-1, and TRAP have a lower risk of developing clinical malaria than children without high levels of these antibodies. The decreased risk of clinical malaria may be mediated in part by prevention of high-density parasitemia. Antibody-mediated protection against human Plasmo-dium falciparum infection and disease was demon