Cerebral Malaria Is Associated with Low Levels of Circulating Endothelial Progenitor Cells in African Children

Ben Gyan Department of Immunology, Noguchi Memorial Institute for Medical Research, Legon, Ghana; Department of Child Health, University of Ghana Medical School, Korle Bu Teaching Hospital, Accra, Ghana; Biostatistics Unit, Feinstein Institute for Medical Research, Manhasset, New York; Division of International Medicine and Infectious Diseases, Department of Medicine, and Howard Hughes Medical Institute, Department of Genetic Medicine, Weill Medical College of Cornell University, New York, New York

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Bamenla Quarm Goka Department of Immunology, Noguchi Memorial Institute for Medical Research, Legon, Ghana; Department of Child Health, University of Ghana Medical School, Korle Bu Teaching Hospital, Accra, Ghana; Biostatistics Unit, Feinstein Institute for Medical Research, Manhasset, New York; Division of International Medicine and Infectious Diseases, Department of Medicine, and Howard Hughes Medical Institute, Department of Genetic Medicine, Weill Medical College of Cornell University, New York, New York

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George O. Adjei Department of Immunology, Noguchi Memorial Institute for Medical Research, Legon, Ghana; Department of Child Health, University of Ghana Medical School, Korle Bu Teaching Hospital, Accra, Ghana; Biostatistics Unit, Feinstein Institute for Medical Research, Manhasset, New York; Division of International Medicine and Infectious Diseases, Department of Medicine, and Howard Hughes Medical Institute, Department of Genetic Medicine, Weill Medical College of Cornell University, New York, New York

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John K. A. Tetteh Department of Immunology, Noguchi Memorial Institute for Medical Research, Legon, Ghana; Department of Child Health, University of Ghana Medical School, Korle Bu Teaching Hospital, Accra, Ghana; Biostatistics Unit, Feinstein Institute for Medical Research, Manhasset, New York; Division of International Medicine and Infectious Diseases, Department of Medicine, and Howard Hughes Medical Institute, Department of Genetic Medicine, Weill Medical College of Cornell University, New York, New York

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Kwadwo Asamoah Kusi Department of Immunology, Noguchi Memorial Institute for Medical Research, Legon, Ghana; Department of Child Health, University of Ghana Medical School, Korle Bu Teaching Hospital, Accra, Ghana; Biostatistics Unit, Feinstein Institute for Medical Research, Manhasset, New York; Division of International Medicine and Infectious Diseases, Department of Medicine, and Howard Hughes Medical Institute, Department of Genetic Medicine, Weill Medical College of Cornell University, New York, New York

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Anastasia Aikins Department of Immunology, Noguchi Memorial Institute for Medical Research, Legon, Ghana; Department of Child Health, University of Ghana Medical School, Korle Bu Teaching Hospital, Accra, Ghana; Biostatistics Unit, Feinstein Institute for Medical Research, Manhasset, New York; Division of International Medicine and Infectious Diseases, Department of Medicine, and Howard Hughes Medical Institute, Department of Genetic Medicine, Weill Medical College of Cornell University, New York, New York

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Daniel Dodoo Department of Immunology, Noguchi Memorial Institute for Medical Research, Legon, Ghana; Department of Child Health, University of Ghana Medical School, Korle Bu Teaching Hospital, Accra, Ghana; Biostatistics Unit, Feinstein Institute for Medical Research, Manhasset, New York; Division of International Medicine and Infectious Diseases, Department of Medicine, and Howard Hughes Medical Institute, Department of Genetic Medicine, Weill Medical College of Cornell University, New York, New York

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Martin L. Lesser Department of Immunology, Noguchi Memorial Institute for Medical Research, Legon, Ghana; Department of Child Health, University of Ghana Medical School, Korle Bu Teaching Hospital, Accra, Ghana; Biostatistics Unit, Feinstein Institute for Medical Research, Manhasset, New York; Division of International Medicine and Infectious Diseases, Department of Medicine, and Howard Hughes Medical Institute, Department of Genetic Medicine, Weill Medical College of Cornell University, New York, New York

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Cristina P. Sison Department of Immunology, Noguchi Memorial Institute for Medical Research, Legon, Ghana; Department of Child Health, University of Ghana Medical School, Korle Bu Teaching Hospital, Accra, Ghana; Biostatistics Unit, Feinstein Institute for Medical Research, Manhasset, New York; Division of International Medicine and Infectious Diseases, Department of Medicine, and Howard Hughes Medical Institute, Department of Genetic Medicine, Weill Medical College of Cornell University, New York, New York

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Sanchita Das Department of Immunology, Noguchi Memorial Institute for Medical Research, Legon, Ghana; Department of Child Health, University of Ghana Medical School, Korle Bu Teaching Hospital, Accra, Ghana; Biostatistics Unit, Feinstein Institute for Medical Research, Manhasset, New York; Division of International Medicine and Infectious Diseases, Department of Medicine, and Howard Hughes Medical Institute, Department of Genetic Medicine, Weill Medical College of Cornell University, New York, New York

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Marion E. Howard Department of Immunology, Noguchi Memorial Institute for Medical Research, Legon, Ghana; Department of Child Health, University of Ghana Medical School, Korle Bu Teaching Hospital, Accra, Ghana; Biostatistics Unit, Feinstein Institute for Medical Research, Manhasset, New York; Division of International Medicine and Infectious Diseases, Department of Medicine, and Howard Hughes Medical Institute, Department of Genetic Medicine, Weill Medical College of Cornell University, New York, New York

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Elizabeth Milbank Department of Immunology, Noguchi Memorial Institute for Medical Research, Legon, Ghana; Department of Child Health, University of Ghana Medical School, Korle Bu Teaching Hospital, Accra, Ghana; Biostatistics Unit, Feinstein Institute for Medical Research, Manhasset, New York; Division of International Medicine and Infectious Diseases, Department of Medicine, and Howard Hughes Medical Institute, Department of Genetic Medicine, Weill Medical College of Cornell University, New York, New York

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Kimberly Fischer Department of Immunology, Noguchi Memorial Institute for Medical Research, Legon, Ghana; Department of Child Health, University of Ghana Medical School, Korle Bu Teaching Hospital, Accra, Ghana; Biostatistics Unit, Feinstein Institute for Medical Research, Manhasset, New York; Division of International Medicine and Infectious Diseases, Department of Medicine, and Howard Hughes Medical Institute, Department of Genetic Medicine, Weill Medical College of Cornell University, New York, New York

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Shahin Rafii Department of Immunology, Noguchi Memorial Institute for Medical Research, Legon, Ghana; Department of Child Health, University of Ghana Medical School, Korle Bu Teaching Hospital, Accra, Ghana; Biostatistics Unit, Feinstein Institute for Medical Research, Manhasset, New York; Division of International Medicine and Infectious Diseases, Department of Medicine, and Howard Hughes Medical Institute, Department of Genetic Medicine, Weill Medical College of Cornell University, New York, New York

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David Jin Department of Immunology, Noguchi Memorial Institute for Medical Research, Legon, Ghana; Department of Child Health, University of Ghana Medical School, Korle Bu Teaching Hospital, Accra, Ghana; Biostatistics Unit, Feinstein Institute for Medical Research, Manhasset, New York; Division of International Medicine and Infectious Diseases, Department of Medicine, and Howard Hughes Medical Institute, Department of Genetic Medicine, Weill Medical College of Cornell University, New York, New York

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Linnie M. Golightly Department of Immunology, Noguchi Memorial Institute for Medical Research, Legon, Ghana; Department of Child Health, University of Ghana Medical School, Korle Bu Teaching Hospital, Accra, Ghana; Biostatistics Unit, Feinstein Institute for Medical Research, Manhasset, New York; Division of International Medicine and Infectious Diseases, Department of Medicine, and Howard Hughes Medical Institute, Department of Genetic Medicine, Weill Medical College of Cornell University, New York, New York

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Damage to the cerebral microvasculature is a feature of cerebral malaria. Circulating endothelial progenitor cells are needed for microvascular repair. Based on this knowledge, we hypothesized that the failure to mobilize sufficient circulating endothelial progenitor cells to the cerebral microvasculature is a pathophysiologic feature of cerebral malaria. To test this hypothesis, we compared peripheral blood levels of CD34 +/VEGFR2+ and CD34 +/CD133+ cells and plasma levels of the chemokine stromal cell–derived growth factor 1 (SDF-1) in 214 children in Accra, Ghana. Children with cerebral malaria had lower levels of CD34 +/VEGFR2+ and CD34 +/CD133+ cells compared with those with uncomplicated malaria, asymptomatic parasitemia, or healthy controls. SDF-1 levels were higher in children with acute malaria compared with healthy controls. Together, these results uncover a potentially novel role for endothelial progenitor cell mobilization in the pathophysiology of cerebral malaria.

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