title: Toward a surrogate marker of malaria exposure: modeling longitudinal antibody measurements under outbreak conditions.
abstract: BACKGROUND
  Biomarkers of exposure to Plasmodium falciparum would be a useful tool for the assessment of malaria burden and analysis of intervention and epidemiological studies. Antibodies to pre-erythrocytic antigens represent potential surrogates of exposure.
  
  
  RESULTS
  In an outbreak cohort of U.S. Marines deployed to Liberia, we modeled pre- and post-deployment IgG against P. falciparum sporozoites by immunofluorescence antibody test, and both IgG and IgM against the P. falciparum circumsporozoite protein by enzyme-linked immunosorbant assay. Modeling seroconversion thresholds by a fixed ratio, linear regression or nonlinear regression produced sensitivity for identification of exposed U.S. Marines between 58-70% and specificities between 87-97%, compared with malaria-naïve U.S. volunteers. Exposure was predicted in 30-45% of the cohort.
  
  
  CONCLUSIONS
  Each of the three models tested has merits in different studies, but further development and validation in endemic populations is required. Overall, these models provide support for an antibody-based surrogate marker of exposure to malaria.
authors.affiliation: Naval Medical Research Center, Silver Spring, Maryland, United States of America. joe.campo@cresib.cat
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Campo
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Whitman
authors.forename: Daniel
authors.initials: D
authors.lastname: Freilich
authors.forename: Timothy H
authors.initials: TH
authors.lastname: Burgess
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Martin
authors.forename: Denise L
authors.initials: DL
authors.lastname: Doolan
mesh_terms: D000913:Antibodies, Protozoan / Q000276:immunology*; D015415:Biomarkers / Q000378:metabolism; D004196:Disease Outbreaks; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007988:Liberia; D008137:Longitudinal Studies; D016778:Malaria, Falciparum / Q000175:diagnosis / Q000453:epidemiology* / Q000276:immunology* / Q000469:parasitology; D008889:Military Personnel; D018448:Models, Immunological; D010963:Plasmodium falciparum / Q000276:immunology; D015800:Protozoan Proteins / Q000276:immunology; D012680:Sensitivity and Specificity; D014838:Volunteers
chemical_list: D000913:Antibodies, Protozoan; D015415:Biomarkers; D007074:Immunoglobulin G; D015800:Protozoan Proteins