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

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.

Received September 10, 2008. Accepted for publication November 6, 2008.

Acknowledgments: The authors thank Tatiana Peshansky for bioinformatics support, Marshall Glesby and William Rogers for useful discussions, and Warren Johnson, Dan Fitzgerald, Kyu Rhee, Jorgen Kurtzhals, and Heidi Stuhlmann for critical review of the manuscript.

Financial support: The study was funded by the National Institutes of Health NS054243 with support from the Weill Medical College General Clinical Research Center (MO1 RR00047).

^* Address correspondence to Linnie Golightly, Weill Medical College of Cornell University, Division of International Medicine and Infectious Diseases, 1300 York Avenue, Room A421, New York, NY 10021. E-mail: lgolight{at}med.cornell.edu

Authors’ addresses: Ben Gyan, John K. A. Tetteh, Kwadwo Asamoah Kusi, Anastasia Aikins, and Daniel Dodoo, Department of Immunology, Noguchi Memorial Institute for Medical Research, Box LG581, Legon, Ghana, Tel: 233-21-501178, Fax: 233-21-502182. Bamenla Quarm Goka and George O. Adjei, Department of Child Health, University of Ghana Medical School, Korle Bu Teaching Hospital, PO Box KB 4236, Accra, Ghana, Tel: 233-21-665405, Fax: 233-21-668425. Martin L. Lesser and Cristina P. Sison, Biostatistics Unit, Feinstein Institute for Medical Research, North Shore-LIJ Health System, 1129 Northern Blvd., Suite 302, Manhasset, NY 11030, Tel: 516-240-8300, Fax: 516-240-8344. Shahin Rafii and David Jin, Howard Hughes Medical Institute, Weill Medical College of Cornell University, 1300 York Avenue, Room A-869A, New York, NY 10021, Tel: 212-746-2070, Fax: 212-746-2286. Sanchita Das, Marion E. Howard, Elizabeth Milbank, Kimberly Fischer, and Linnie M. Golightly, Division of International Medicine and Infectious Diseases, Department of Medicine, Weill Medical College of Cornell University, 1300 York Avenue, Room A421, New York, NY 10021, Tel: 212-746-6320, Fax: 212-746-8675, E-mail: lgolight{at}med.cornell.edu.