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Parasite Immunol. 2017 Jul;39(7). doi: 10.1111/pim.12438. Epub 2017 May 28.

Elevated cerebrospinal fluid tumour necrosis factor is associated with acute and long-term neurocognitive impairment in cerebral malaria.

Author information

1
Department of Pediatrics, Division of Global Pediatrics, University of Minnesota, Minneapolis, MN, USA.
2
Ryan White Center for Pediatric Infectious Disease and Global Health, Department of Pediatrics, Indiana University, Indianapolis, IN, USA.
3
Department of Microbiology, Makerere University, Kampala, Uganda.
4
Department of Pediatrics and Child Health, Makerere University, Kampala, Uganda.
5
Department of Psychiatry, Makerere University, Kampala, Uganda.
6
Department of Medicine, University of Minnesota Medical School, Minneapolis, MN, USA.

Abstract

Systemic tumour necrosis factor-α (TNF-α) may contribute to the pathogenesis of cerebral malaria (CM) by promoting endothelial activation and parasite sequestration. However, less is known about the role of central nervous system (CNS) TNF-α in CM. We assessed plasma (n=249) and cerebrospinal fluid (CSF) (n=167) TNF-α levels in Ugandan children with CM, plasma TNF-α in Ugandan community control children (n=198) and CSF TNF-α in North American control children who had recovered from leukaemia (n=13). Plasma and CSF TNF-α were measured by magnetic bead assay. We compared plasma and CSF TNF-α levels in children with CM to mortality, acute and chronic neurologic deficits and long-term neurocognitive impairment. Plasma and CSF TNF-α levels were higher in CM than control children (P<.0001 for both). CSF TNF-α levels were higher in children who had neurologic deficits at discharge or 6-month follow-up (P≤.05 for both). Elevated CSF but not plasma TNF-α was associated with longer coma duration (Spearman's rho .18, P=.02) and deficits in overall cognition in children 5 years and older (β coefficient -.74, 95% CI -1.35 to -0.13, P=.02). The study findings suggest that CNS TNF-α may be involved in the development of acute and chronic neurologic and cognitive sequelae in children with CM.

KEYWORDS:

neurocognitive impairment; paediatric cerebral malaria; tumour necrosis factor-alpha

PMID:
28453871
PMCID:
PMC5492989
DOI:
10.1111/pim.12438
[Indexed for MEDLINE]
Free PMC Article

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