Toward a surrogate marker of malaria exposure: modeling longitudinal antibody measurements under outbreak conditions

PLoS One. 2011;6(7):e21826. doi: 10.1371/journal.pone.0021826. Epub 2011 Jul 27.

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.

Methods and findings: 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.

Conclusion: 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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Antibodies, Protozoan / immunology*
  • Biomarkers / metabolism
  • Disease Outbreaks*
  • Humans
  • Immunoglobulin G / immunology
  • Liberia
  • Longitudinal Studies
  • Malaria, Falciparum / diagnosis
  • Malaria, Falciparum / epidemiology*
  • Malaria, Falciparum / immunology*
  • Malaria, Falciparum / parasitology
  • Military Personnel
  • Models, Immunological*
  • Plasmodium falciparum / immunology
  • Protozoan Proteins / immunology
  • Sensitivity and Specificity
  • Volunteers

Substances

  • Antibodies, Protozoan
  • Biomarkers
  • Immunoglobulin G
  • Protozoan Proteins