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Antibody Profiles to P. falciparum Antigens Over Time Characterize Acute and Long-Term Malaria Exposure in an Area of Low and Unstable Transmission

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  • 1 Department of Biochemistry and Molecular Biology, Egerton University, Nakuru, Kenya;
  • | 2 Centre for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya;
  • | 3 Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, Maryland;
  • | 4 Division of Global Pediatrics, University of Minnesota, Minneapolis, Minnesota;
  • | 5 Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, Minnesota;
  • | 6 CDC Foundation, Atlanta, Georgia;
  • | 7 Department of Medicine, University of Minnesota, Minneapolis, Minnesota;
  • | 8 Hennepin Healthcare Research Institute, Minneapolis, Minnesota;
  • | 9 School of Health Sciences, Jaramogi Oginga Odinga University of Science and Technology, Siaya, Kenya;
  • | 10 Department of Parasites and Insect Vectors, Institut Pasteur, Paris, France;
  • | 11 Ryan White Center for Pediatric Infectious Diseases and Global Health, Indiana University School of Medicine, Indianapolis, Indiana

ABSTRACT

Prevalence and levels of antibodies to multiple Plasmodium falciparum antigens show promise as tools for estimating malaria exposure. In a highland area of Kenya with unstable transmission, we assessed the presence and levels of antibodies to 12 pre-erythrocytic and blood-stage P. falciparum antigens by multiplex cytometric bead assay or ELISA in 604 individuals in August 2007, with follow-up testing in this cohort in April 2008, April 2009, and May 2010. Four hundred individuals were tested at all four time points. During this period, the only substantial malaria incidence occurred from April to August 2009. Antibody prevalence in adults was high at all time points (> 70%) for apical membrane antigen 1, erythrocyte-binding antigen 175, erythrocyte-binding protein-2, glutamate rich protein (GLURP)-R2, merozoite surface protein (MSP) 1 (19), MSP-1 (42), and liver-stage antigen-1; moderate (30–70%) for GLURP-R0, MSP-3, and thrombospondin-related adhesive protein; and low (< 30%) for SE and circumsporozoite protein (CSP). Changes in community-wide malaria exposure were best reflected in decreasing antibody levels overtime for highly immunogenic antigens, and in antibody seroprevalence overtime for the less-immunogenic antigens. Over the 3 years, antibody levels to all antigens except CSP and schizont extract (SE) decreased in an age-dependent manner. Prevalence and levels of antibodies to all antigens except CSP and SE increased with age. Increases in antibody prevalence and levels to CSP and SE coincided with increases in community-wide malaria incidence. Antibody levels to multiple P. falciparum antigens decrease in the absence of consistent transmission. Multiplex assays that assess both the presence and level of antibodies to multiple pre-erythrocytic and blood-stage P. falciparum antigens may provide the most useful estimates of past and recent malaria transmission in areas of unstable transmission and could be useful tools in malaria control and elimination campaigns.

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Author Notes

Address correspondence to Chandy C. John, Ryan White Center for Pediatric Infectious Diseases and Global Health, Indiana University School of Medicine, 1044 W. Walnut St., R4 402D, Indianapolis, IN 46202. E-mail: chjohn@iu.edu

Disclaimer: The content is solely the responsibility of the authors and does not represent views of the funders.

Financial support: This work was supported by grants to C. C. J. from the National Institute of Allergy and Infectious Diseases (U01 AI056270) and the Fogarty International Center (D43 TW0080085 and R25 TW009345 awarded to the Northern Pacific Global Health Fellows Program) as well as an Amplatz award from the University of Minnesota and funding from the Riley Children’s Foundation.

Authors’ addresses: Bartholomew N. Ondigo, Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, MD, E-mail: ondigo2002@gmail.com. Karen E. S. Hamre, CDC Foundation, Atlanta, GA, E-mail: mry0@cdc.gov. Anne E. P. Frosch, Hennepin Healthcare Research Institute, Minneapolis, MN, E-mail: apfrosch@gmail.com. George Ayodo, Centre for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya, E-mail: gayodo@gmail.com. Michael T. White, Department of Parasites and Insect Vectors, Institut Pasteur, Paris, France, E-mail: michael.white@pasteur.fr. Chandy C. John, Department of Pediatrics, Indiana University, Indianapolis, IN, E-mail: chjohn@iu.edu.

These authors contributed equally to this work.

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