Estimation of recent and long-term malaria transmission in a population by antibody testing to multiple Plasmodium falciparum antigens.

BACKGROUND: Tools that estimate recent and long-term malaria transmission in a population would be highly useful for malaria elimination programs. METHODS: The prevalence of antibodies to 11 Plasmodium falciparum antigens was assessed by cytometric bead assay or enzyme-linked immunosorbent assay in 1000 people in a highland area of Kenya over 14 months, during a period of interrupted malaria transmission. RESULTS: Antibodies differed by antigen in acquisition with age: rapid (>80% antibody positive by age 20 years, 5 antigens), moderate (>40% positive by age 20 years, 3 antigens), or slow (<40% positive by age 20 years, 3 antigens). Antibody seroreversion rates in the 14 months between samples decreased with age rapidly (7 antigens), slowly (3 antigens), or remained high at all ages (schizont extract). Estimated antibody half-lives in individuals >10 years of age were long (40 to >80 years) for 5 antigens, moderate (5-20 years) for 3 antigens, and short (<1 year) for 3 antigens. CONCLUSIONS: Antibodies to P. falciparum antigens in malaria-endemic areas vary by age, antigen, and time since last exposure to P. falciparum. Multiplex P. falciparum antibody testing could provide estimates of long-term and recent malaria transmission and potentially of a population's susceptibility to future clinical malaria.

Evidence of Endothelial Activation in Asymptomatic Plasmodium falciparum Parasitemia and Effect of Blood Group on Levels of von Willebrand Factor in Malaria.

BACKGROUND: Endothelial activation may contribute to development of severe disease from Plasmodium falciparum infection, but optimal markers of endothelial activation in severe malaria, the extent of endothelial activation in asymptomatic infection, and the effect of blood group O on endothelial activation have not been defined. METHODS: Serum levels of 3 markers of endothelial activation-von Willebrand factor (VWF), soluble intercellular adhesion molecule-1 (sICAM-1), and soluble vascular cell adhesion molecule-1 (sVCAM-1)-were assessed in Ugandan children with cerebral malaria (CM) (n = 86), children with uncomplicated malaria (UM) (n = 81), and community children (CC) (n = 90). RESULTS: Serum VWF, sICAM-1, and sVCAM-1 levels were all elevated in asymptomatic community children with microscopy-confirmed parasitemia when compared with children without parasitemia by microscopy or polymerase chain reaction (all, P ≤ .05). Levels of VWF, sICAM-1, and sVCAM-1 were higher in children with UM than in CC (all, P < 0.001), but only VWF levels effectively distinguished CM from UM (P < 0.001), a finding confirmed by receiver operating characteristic analyses (area under the curve = 0.67; 95% confidence interval, .58-.75). Von Willebrand factor levels were lower in children with blood group O versus non-O blood groups across the disease spectrum, but VWF levels remained higher in CM versus UM, even after controlling for blood group. CONCLUSIONS: Endothelial activation, as assessed by serum levels of VWF, sICAM-1, and sVCAM-1, occurs even in subclinical P. falciparum parasitemia. Von Willebrand factor levels increase with greater malaria disease severity. Blood group O is associated with lower VWF levels, but presence of blood group O alone does not explain the higher VWF levels seen in children with CM.