Determination of Plasmodium vivax and Plasmodium falciparum Malaria Exposure in Two Ethiopian Communities and Its Relationship to Duffy Expression

Lauren Bradley Department of Ecology and Evolutionary Biology, School of Biological Sciences, University of California, Irvine, California;

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Delenasaw Yewhalaw Department of Medical Laboratory Sciences and Pathology, College of Health Sciences, Jimma University, Jimma, Ethiopia;
Tropical and Infectious Diseases Research Center, Jimma University, Jimma, Ethiopia;

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Elizabeth Hemming-Schroeder Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, Colorado;

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Paula Embury Center for Global Health and Disease, Case Western Reserve University, Cleveland, Ohio;

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Ming-Chieh Lee Program in Public Health, College of Health Sciences, University of California, Irvine, California;

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Endalew Zemene Tropical and Infectious Diseases Research Center, Jimma University, Jimma, Ethiopia;

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Teshome Degefa School of Medical Laboratory Sciences, Faculty of Health Sciences, Jimma University, Jimma, Ethiopia

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Christopher King Center for Global Health and Disease, Case Western Reserve University, Cleveland, Ohio;

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James Kazura Center for Global Health and Disease, Case Western Reserve University, Cleveland, Ohio;

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Guiyun Yan Department of Ecology and Evolutionary Biology, School of Biological Sciences, University of California, Irvine, California;
Program in Public Health, College of Health Sciences, University of California, Irvine, California;

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Arlene Dent Center for Global Health and Disease, Case Western Reserve University, Cleveland, Ohio;

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ABSTRACT.

Despite historical dogma that Duffy blood group negativity of human erythrocytes confers resistance to Plasmodium vivax blood stage infection, cases of P. vivax malaria and asymptomatic blood stage infection (subclinical malaria) have recently been well documented in Duffy-negative individuals throughout Africa. However, the impact of Duffy negativity on the development of naturally acquired immunity to P. vivax remains poorly understood. We examined antibody reactivity to P. vivax and P. falciparum antigens at two field sites in Ethiopia and assessed Duffy gene expression by polymerase chain reaction amplification and sequencing of the GATA-1 transcription factor–binding site of the Duffy antigen receptor for chemokines (DARC) gene promotor region that is associated with silencing of erythroid cell transcription and absent protein expression. Antibodies to three of the four P. vivax blood stage antigens examined, RBP2b, EBP2, and DBPIISal-1, were significantly lower (P < 0.001) in Duffy-negative individuals relative to Duffy-positive individuals. In stark contrast, no clear pattern was found across Duffy-negative and Duffy-positive genotypes for P. falciparum antibodies. We conclude that lack of erythroid Duffy expression is associated with reduced serologic responses, indicative of less naturally acquired immunity and less cumulative exposure to blood stage P. vivax parasites relative to Duffy positive individuals living in the same communities.

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Author Notes

Financial support: This study was funded by the NIH (U19 AI129326 and D43 TW001505). The funders did not have a role in study design or development, data collection and analysis, publication process, or manuscript preparation. L. B. is supported by 5 F31 AI161887-02.

Disclaimer: This work was presented in part at the American Society for Tropical Medicine and Hygiene Annual Meeting 2021.

Authors’ addresses: Lauren Bradley, Department of Ecology and Evolutionary Biology, University of California, Irvine, CA, E-mail: lbradle1@uci.edu. Delenasaw Yewhalaw, Department of Medical Laboratory Sciences and Pathology, College of Health Sciences, and Tropical and Infectious Diseases Research Center, Jimma University, Jimma, Ethiopia, E-mail: delenasawye@yahoo.com. Elizabeth Hemming-Schroeder, Center for Vector-Borne Infectious Diseases, Colorado State University, Fort Collins, CO, E-mail: Elizabeth.Hemming-Schroeder@colostate.edu. Paula Embury, Christopher King, James Kazura, and Arlene Dent, Center for Global Health and Disease, Case Western Reserve University, Cleveland, OH, E-mails: pbe@case.edu, cxk21@case.edu, jxk14@case.edu, and aed9@case.edu. Ming-Chieh Lee, Program in Public Health, College of Health Sciences, University of California, Irvine, CA, E-mail: mingchil@uci.edu. Endalew Zemene, Tropical and Infectious Diseases Research Center, Jimma University, Jimma, Ethiopia, E-mail: endalew2005@yahoo.com. Teshome Degefa, School of Medical Laboratory Sciences, Faculty of Health Sciences, Jimma University, Jimma, Ethiopia, E-mail: teshedege@gmail.com. Guiyun Yan, Department of Ecology and Evolutionary Biology, School of Biological Sciences and Program in Public Health, College of Health Sciences, University of California, Irvine, CA, E-mail: guiyuny@hs.uci.edu.

Address correspondence to Arlene Dent, Biomedical Research Building, Suite 425, 2109 Adelbert Road, Cleveland, OH 44106. E-mail: aed9@case.edu
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