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Toward a Surrogate Marker of Malaria Exposure: Modeling Longitudinal Antibody Measurements under Outbreak Conditions

Authors
Journal
PLoS ONE
1932-6203
Publisher
Public Library of Science
Publication Date
Volume
6
Issue
7
Identifiers
DOI: 10.1371/journal.pone.0021826
Keywords
  • Research Article
  • Biology
  • Immunology
  • Immunity
  • Humoral Immunity
  • Immunoglobulins
  • Microbiology
  • Medicine
  • Epidemiology
  • Biomarker Epidemiology
  • Infectious Disease Epidemiology
  • Infectious Diseases
  • Parasitic Diseases
  • Malaria
  • Plasmodium Falciparum
  • Infectious Disease Modeling
Disciplines
  • Biology
  • Medicine

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.

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