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Proc Natl Acad Sci U S A. 2015 Aug 11;112(32):E4438-47. doi: 10.1073/pnas.1501705112. Epub 2015 Jul 27.

Novel serologic biomarkers provide accurate estimates of recent Plasmodium falciparum exposure for individuals and communities.

Author information

  • 1Department of Medicine, University of California, San Francisco, CA 94110; Division of Infectious Diseases, School of Public Health, University of California, Berkeley, CA 94720; Global Health Group, University of California, San Francisco, CA 94158;
  • 2Department Immunology and Infection, London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom;
  • 3Division of Infectious Diseases, Department of Medicine, University of California, Irvine, CA 92697;
  • 4Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20852;
  • 5Division of Biostatistics, School of Public Health, University of California, Berkeley, CA 94720;
  • 6Infectious Diseases Research Collaboration, Kampala, Uganda;
  • 7Department of Medicine, Makerere University College of Health Sciences, Kampala, Uganda;
  • 8Center for Biomedical Research, Burnet Institute for Medical Research and Public Health, Melbourne, VIC, Canada 3004;
  • 9Center for Global Health, Centers for Disease Control and Prevention, Atlanta, GA 30333;
  • 10Spatial Ecology and Epidemiology Group, Department of Zoology, University of Oxford, Oxford OX1 3PS, United Kingdom; Sanaria Institute for Global Health and Tropical Medicine, Rockville, MD 20850.
  • 11Department of Medicine, University of California, San Francisco, CA 94110;
  • 12Department of Medicine, University of California, San Francisco, CA 94110; bryan.greenhouse@ucsf.edu.

Abstract

Tools to reliably measure Plasmodium falciparum (Pf) exposure in individuals and communities are needed to guide and evaluate malaria control interventions. Serologic assays can potentially produce precise exposure estimates at low cost; however, current approaches based on responses to a few characterized antigens are not designed to estimate exposure in individuals. Pf-specific antibody responses differ by antigen, suggesting that selection of antigens with defined kinetic profiles will improve estimates of Pf exposure. To identify novel serologic biomarkers of malaria exposure, we evaluated responses to 856 Pf antigens by protein microarray in 186 Ugandan children, for whom detailed Pf exposure data were available. Using data-adaptive statistical methods, we identified combinations of antibody responses that maximized information on an individual's recent exposure. Responses to three novel Pf antigens accurately classified whether an individual had been infected within the last 30, 90, or 365 d (cross-validated area under the curve = 0.86-0.93), whereas responses to six antigens accurately estimated an individual's malaria incidence in the prior year. Cross-validated incidence predictions for individuals in different communities provided accurate stratification of exposure between populations and suggest that precise estimates of community exposure can be obtained from sampling a small subset of that community. In addition, serologic incidence predictions from cross-sectional samples characterized heterogeneity within a community similarly to 1 y of continuous passive surveillance. Development of simple ELISA-based assays derived from the successful selection strategy outlined here offers the potential to generate rich epidemiologic surveillance data that will be widely accessible to malaria control programs.

KEYWORDS:

Plasmodium falciparum malaria; antigen discovery; epidemiology; immunoepidemiology; serology

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