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          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.

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          Author and article information

          Journal
          Proc. Natl. Acad. Sci. U.S.A.
          Proceedings of the National Academy of Sciences of the United States of America
          1091-6490
          0027-8424
          Aug 11 2015
          : 112
          : 32
          Affiliations
          [1 ] Department 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;
          [2 ] Department Immunology and Infection, London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom;
          [3 ] Division of Infectious Diseases, Department of Medicine, University of California, Irvine, CA 92697;
          [4 ] Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20852;
          [5 ] Division of Biostatistics, School of Public Health, University of California, Berkeley, CA 94720;
          [6 ] Infectious Diseases Research Collaboration, Kampala, Uganda;
          [7 ] Department of Medicine, Makerere University College of Health Sciences, Kampala, Uganda;
          [8 ] Center for Biomedical Research, Burnet Institute for Medical Research and Public Health, Melbourne, VIC, Canada 3004;
          [9 ] Center for Global Health, Centers for Disease Control and Prevention, Atlanta, GA 30333;
          [10 ] Spatial 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.
          [11 ] Department of Medicine, University of California, San Francisco, CA 94110;
          [12 ] Department of Medicine, University of California, San Francisco, CA 94110; bryan.greenhouse@ucsf.edu.
          Article
          1501705112
          10.1073/pnas.1501705112
          26216993
          84598ef9-375a-427a-af1e-15df96149017
          History

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

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