title: Antibodies to Plasmodium falciparum erythrocyte-binding antigen-175 are associated with protection from clinical malaria.
abstract: BACKGROUND
  Antibodies to blood-stage Plasmodium falciparum antigens have been associated with protection against clinical malaria in some studies but not others. Many of these studies have not assessed whether high-titer antibodies are associated with protection and have not adjusted for differences in malaria exposure.
  
  
  METHODS
  The presence of high-titer antibodies to apical membrane antigen-1, erythrocyte-binding antigen-175 (EBA-175), and merozoite surface protein-1₁₉ (MSP-1₁₉) was assessed in 87 children living in a malaria holoendemic area of Kenya. The children were prospectively assessed during 1 year for clinical malaria.
  
  
  RESULTS
  In unadjusted analyses, high-titer antibodies to MSP-1₁₉, but not EBA-175 or apical membrane antigen-1, were associated with protection from clinical malaria. However, after adjustment for exposure, only high-titer antibodies to EBA-175 were associated with protection from clinical malaria (hazard ratio, 0.48; 95% confidence interval [CI], 0.24, 0.95; P = 0.03), and with reduced episodes of clinical malaria (incidence rate ratio, 0.50; 95% CI, 0.31, 0.81; P = 0.005). A trend toward increased protection from clinical malaria in children was seen with antibodies to both EBA-175 and MSP-1₁₉ (hazard ratio, 0.26; 95% CI, 0.03, 1.94; P = 0.18).
  
  
  CONCLUSIONS
  High-titer antibodies to EBA-175 are associated with protection from clinical malaria in children in a malaria holoendemic area of Kenya. Accurate estimates of antibody-associated protection from clinical malaria require adjustment for malaria exposure.
authors.affiliation: Division of Global Pediatrics, Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN 55414, USA.
authors.forename: Matthew B
authors.initials: MB
authors.lastname: McCarra
authors.forename: George
authors.initials: G
authors.lastname: Ayodo
authors.forename: Peter O
authors.initials: PO
authors.lastname: Sumba
authors.forename: James W
authors.initials: JW
authors.lastname: Kazura
authors.forename: Ann M
authors.initials: AM
authors.lastname: Moormann
authors.forename: David L
authors.initials: DL
authors.lastname: Narum
authors.forename: Chandy C
authors.initials: CC
authors.lastname: John
mesh_terms: D000913:Antibodies, Protozoan / Q000097:blood / Q000276:immunology; D000953:Antigens, Protozoan / Q000097:blood / Q000276:immunology*; D016009:Chi-Square Distribution; D002648:Child; D002675:Child, Preschool; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007223:Infant; D053208:Kaplan-Meier Estimate; D007630:Kenya / Q000453:epidemiology; D016778:Malaria, Falciparum / Q000097:blood / Q000453:epidemiology / Q000276:immunology* / Q000469:parasitology; D008565:Membrane Proteins / Q000097:blood / Q000276:immunology; D020066:Merozoite Surface Protein 1 / Q000097:blood / Q000276:immunology; D010963:Plasmodium falciparum / Q000276:immunology*; D015800:Protozoan Proteins / Q000097:blood / Q000276:immunology*; D012307:Risk Factors
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D007074:Immunoglobulin G; D008565:Membrane Proteins; D020066:Merozoite Surface Protein 1; D015800:Protozoan Proteins; C090077:apical membrane antigen I, Plasmodium; C065668:erythrocyte-binding antigen 175, Plasmodium