Serologic and Cytokine Profiles of Children with Concurrent Cerebral Malaria and Severe Malarial Anemia Are Distinct from Other Subtypes of Severe Malaria

Rafal S. Sobota Malaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, Maryland;
Ken and Ruth Davee Department of Neurology, Northwestern University, Chicago, Illinois;

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Abby R. Goron Malaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, Maryland;

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Andrea A. Berry Malaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, Maryland;

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Jason A. Bailey Malaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, Maryland;

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Drissa Coulibaly Malaria Research and Training Center, University of Sciences, Techniques and Technologies, Bamako, Mali;

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Matthew Adams Malaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, Maryland;

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Abdoulaye K. Kone Malaria Research and Training Center, University of Sciences, Techniques and Technologies, Bamako, Mali;

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Bourema Kouriba Malaria Research and Training Center, University of Sciences, Techniques and Technologies, Bamako, Mali;

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Ogobara K. Doumbo Malaria Research and Training Center, University of Sciences, Techniques and Technologies, Bamako, Mali;

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Marcelo B. Sztein Malaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, Maryland;

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Philip L. Felgner Division of Infectious Diseases, Department of Medicine, University of California, Irvine, California

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Christopher V. Plowe Malaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, Maryland;

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Kirsten E. Lyke Malaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, Maryland;

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Mahamadou A. Thera Malaria Research and Training Center, University of Sciences, Techniques and Technologies, Bamako, Mali;

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Mark A. Travassos Malaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, Maryland;

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ABSTRACT.

We used a protein microarray featuring Plasmodium falciparum field variants of a merozoite surface antigen to examine malaria exposure in Malian children with different severe malaria syndromes. Unlike children with cerebral malaria alone or severe malarial anemia alone, those with concurrent cerebral malaria and severe malarial anemia had serologic responses demonstrating a broader prior parasite exposure pattern than matched controls with uncomplicated disease. Comparison of levels of malaria-related cytokines revealed that children with the concurrent phenotype had elevated levels of interleukin (IL)-6, IL-8, and IL-10. Our results suggest that the pathophysiology of this severe subtype is unique and merits further investigation.

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Author Notes

Address correspondence to Mark A. Travassos, Malaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, 685 West Baltimore Street, Room 480, Baltimore, MD 21201. E-mail: mtravass@som.umaryland.edu

These authors contributed equally to this work.

Deceased.

These authors contributed equally to this work.

Financial support: This work was supported by National Institutes of Health (NIH) grants R01HL130750 and R01HL146377 (National Heart, Lung, and Blood Institute); cooperative agreement U19AI065683 (NIH National Institute of Allergy and Infectious Diseases ); NIH National Institute of Allergy and Infectious Diseases grant R01AI099628; a Burroughs Wellcome Fund/American Society of Tropical Medicine and Hygiene Postdoctoral Fellowship to M. A. T.; and an award to C. V. P. from the Howard Hughes Medical Institute. This research was supported by a subproject to R. S. S. on NIH R25NS070695.

Authors’ addresses: Rafal S. Sobota, Ken and Ruth Davee Department of Neurology, Northwestern University, Chicago, IL, E-mail: rafal4484@gmail.com. Abby R. Goron, Johns Hopkins University, Baltimore, MD, E-mail: agoron1@jhmi.edu. Andrea A. Berry, Jason A. Bailey, Matthew Adams, Marcelo B. Sztein, Christopher V. Plowe, Kirsten E. Lyke, and Mark A. Travassos, Malaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, E-mails: aberry@som.umaryland.edu, jason.bailey.719@gmail.com, madams@som.umaryland.edu, msztein@som.umaryland.edu, klyke@som.umaryland.edu, klyke@som.umaryland.edu, and mtravass@som.umaryland.edu. Drissa Coulibaly, Abdoulaye K. Kone, Bourema Kouriba, and Mahamadou A. Thera, Malaria Research and Training Center, University of Sciences, Techniques and Technologies, Bamako, Mali, E-mail: coulibalyd@icermali.org, akkone@yahoo.fr, kouriba@icermali.org, and mthera@icermali.org. Philip L. Felgner, Division of Infectious Diseases, Department of Medicine, University of California, Irvine, CA, E-mail: pfelgner@uci.edu.

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