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

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


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.

MeSH terms

  • Child
  • Child, Preschool
  • Cognition Disorders / cerebrospinal fluid
  • Cognition Disorders / epidemiology
  • Cognition Disorders / etiology*
  • Cognition Disorders / parasitology
  • Cohort Studies
  • Female
  • Humans
  • Infant
  • Malaria, Cerebral / cerebrospinal fluid
  • Malaria, Cerebral / complications*
  • Malaria, Cerebral / epidemiology
  • Malaria, Cerebral / immunology
  • Male
  • Neurocognitive Disorders / cerebrospinal fluid
  • Neurocognitive Disorders / epidemiology
  • Neurocognitive Disorders / etiology*
  • Neurocognitive Disorders / parasitology
  • Plasmodium falciparum / immunology*
  • Prospective Studies
  • Tumor Necrosis Factor-alpha / blood
  • Tumor Necrosis Factor-alpha / cerebrospinal fluid*
  • Uganda / epidemiology


  • Tumor Necrosis Factor-alpha