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

E. Shabani, B. J. Ouma, R. Idro, P. Bangirana, R. O. Opoka, G. S. Park, A. L. Conroy, C. C. John

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10 Scopus citations


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.

Original languageEnglish (US)
Article numbere12438
JournalParasite Immunology
Issue number7
StatePublished - Jul 2017



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

ASJC Scopus subject areas

  • Parasitology
  • Immunology

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