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Am. J. Trop. Med. Hyg., 78(2), 2008, pp. 198-205
Copyright © 2008 by The American Society of Tropical Medicine and Hygiene

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Cerebrospinal Fluid Cytokine Levels and Cognitive Impairment in Cerebral Malaria

Chandy C. John*, Angela Panoskaltsis-Mortari, Robert O. Opoka, Gregory S. Park, Paul J. Orchard, Anne M. Jurek, Richard Idro, Justus Byarugaba, AND Michael J. Boivin
Department of Pediatrics, University of Minnesota Medical School, Minneapolis, Minnesota; Department of Paediatrics and Child Health, Makerere University Faculty of Medicine, Kampala, Uganda; International Neurologic and Psychiatric Epidemiology Program (INPEP), College of Osteopathic Medicine, Michigan State University, East Lansing, Michigan

Cerebrospinal fluid (CSF) and serum levels of 12 cytokines or chemokines important in central nervous system (CNS) infections were measured in 76 Ugandan children with cerebral malaria (CM) and 8 control children. As compared with control children, children with cerebral malaria had higher cerebrospinal fluid levels of interleukin (IL)-6, CXCL-8/IL-8, granulocyte-colony stimulating factor (G-CSF), tumor necrosis factor-{alpha} (TNF-{alpha}), and IL-1 receptor antagonist. There was no correlation between cerebrospinal and serum cytokine levels for any cytokine except G-CSF. Elevated cerebrospinal fluid but not serum TNF-{alpha} levels on admission were associated with an increased risk of neurologic deficits 3 months later (odds ratio 1.55, 95% CI: 1.10, 2.18, P = 0.01) and correlated negatively with age-adjusted scores for attention (Spearman rho, –0.34, P = 0.04) and working memory (Spearman rho, –0.32, P = 0.06) 6 months later. In children with cerebral malaria, central nervous system TNF-{alpha} production is associated with subsequent neurologic and cognitive morbidity.

Received October 6, 2007. Accepted for publication November 16, 2007.

Acknowledgments: The authors thank the study participants and their families for their participation in this study, and the collaborative study team that performed clinical care and testing, cognitive testing, laboratory investigations, and data entry. This study was supported by an NIH Fogarty Institute grant (R21 TW-006794) to Chandy C. John and a Fulbright African Regional Research Award to Michael J. Boivin. The authors have no financial or other conflicts of interest.

* Address correspondence to Chandy C. John, University of Minnesota, Department of Pediatrics, Global Pediatrics Program, 420 Delaware St., SE, 850 Mayo, MMC-296, Minneapolis, MN 55455. E-mail: ccj{at}umn.edu

Authors’ addresses: Chandy C. John, Angela Panoskaltsis-Mortari, Paul J. Orchard, Gregory S. Park, and Anne M. Jurek, University of Minnesota Department of Pediatrics, 420 Delaware St, SE, 850 Mayo, MMC-296, Minneapolis, MN 55455, Telephone: (612) 624-1966, Fax: (612) 624-8927, E-mails: ccj{at}umn.edu, panos001{at}umn.edu, orcha001{at}umn.edu, parkx479{at}umn.edu, and jurek{at}epi.umn.edu. Robert O. Opoka, Richard Idro, and Justus Byarugaba, Department of Paediatrics and Child Health, Makerere University, Mulago Hospital, Box 7051, Kampala, Uganda, E-mails: opokabob{at}yahoo.com, ridro{at}kilifi.kemri-wellcome.org, and byarugabaj{at}yahoo.com. Michael J. Boivin, International Neurologic and Psychiatric Epidemiology Program (INPEP), College of Osteopathic Medicine, Michigan State University, 324 West Fee Hall, East Lansing, MI 48824, E-mail: Michael.Boivin{at}hc.msu.edu.




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Copyright © 2008 by the American Society of Tropical Medicine and Hygiene.