title: Antibodies to Plasmodium falciparum antigens predict a higher risk of malaria but protection from symptoms once parasitemic.
abstract: BACKGROUND
  Associations between antibody responses to Plasmodium falciparum antigens and protection against symptomatic malaria have been difficult to ascertain, in part because antibodies are potential markers of both exposure to P. falciparum and protection against disease.
  
  
  METHODS
  We measured IgG responses to P. falciparum circumsporozoite protein, liver-stage antigen 1, apical-membrane antigen 1 (AMA-1), and merozoite surface proteins (MSP) 1 and 3, in children in Kampala, Uganda, and measured incidence of malaria before and after antibody measurement.
  
  
  RESULTS
  Stronger responses to all 5 antigens were associated with an increased risk of clinical malaria (P < .01) because of confounding with prior exposure to P. falciparum. However, with use of another assessment, risk of clinical malaria once parasitemic, stronger responses to AMA-1, MSP-1, and MSP-3 were associated with protection (odds ratios, 0.34, 0.36, and 0.31, respectively, per 10-fold increase; P < .01). Analyses assessing antibodies in combination suggested that any protective effect of antibodies was overestimated by associations between individual responses and protection.
  
  
  CONCLUSIONS
  Using the risk of symptomatic malaria once parasitemic as an outcome may improve detection of associations between immune responses and protection from disease. Immunoepidemiology studies designed to detect mechanisms of immune protection should integrate prior exposure into the analysis and evaluate multiple immune responses.
authors.affiliation: Department of Medicine, University of California, San Francisco, CA, USA. bgreenhouse@medsfgh.ucsf.edu
authors.forename: Bryan
authors.initials: B
authors.lastname: Greenhouse
authors.forename: Benjamin
authors.initials: B
authors.lastname: Ho
authors.forename: Alan
authors.initials: A
authors.lastname: Hubbard
authors.forename: Denise
authors.initials: D
authors.lastname: Njama-Meya
authors.forename: David L
authors.initials: DL
authors.lastname: Narum
authors.forename: David E
authors.initials: DE
authors.lastname: Lanar
authors.forename: Sheetij
authors.initials: S
authors.lastname: Dutta
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Rosenthal
authors.forename: Grant
authors.initials: G
authors.lastname: Dorsey
authors.forename: Chandy C
authors.initials: CC
authors.lastname: John
mesh_terms: D000913:Antibodies, Protozoan / Q000097:blood*; D000953:Antigens, Protozoan / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D015994:Incidence; D007223:Infant; D008137:Longitudinal Studies / Q000379:methods; D016778:Malaria, Falciparum / Q000453:epidemiology* / Q000276:immunology / Q000473:pathology* / Q000517:prevention & control; D018512:Parasitemia / Q000453:epidemiology* / Q000276:immunology / Q000473:pathology* / Q000517:prevention & control; D010963:Plasmodium falciparum / Q000276:immunology* / Q000302:isolation & purification; D012307:Risk Factors; D014454:Uganda
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D007074:Immunoglobulin G