Cerebral malaria

Gregory S. Park, Chandy C. John

Research output: Chapter in Book/Report/Conference proceedingChapter


Cerebral malaria (CM), defined as the presence of P. falciparum asexual stages on peripheral blood smear in a person with coma and no other cause for encephalopathy, is estimated to affect more than 800,000 people a year and has a 15-20 % mortality rate. CM predominantly affects children <5 years of age in Africa, but in Southeast Asia it is more common in adolescents and adults. Approximately 25 % of African children with CM develop long-term cognitive impairment. The pathogenesis of cerebral malaria appears to involve several components. The primary factor in pathogenesis of CM is thought to be sequestration, a blockage of microcirculatory vessels in the brain by parasitized red blood cells, along with lesser numbers of leukocytes and platelets. Other factors that appear to be involved in pathogenesis include systemic and central nervous system (CNS) production of proinflammatory cytokines and chemokines, including tumor necrosis factor, interferon-γ, and RANTES; release of free heme during hemolysis; endothelial activation leading to blood-brain barrier breakdown; CNS nitric oxide production; and genetic polymorphisms (e.g., sickle cell trait) that alter these responses or protect in other ways from severe disease. Murine models of cerebral malaria have provided new insights into the disease, but the difference in the parasite species and the host response has limited translation of findings from murine models into human CM studies. Nonhuman primate models are closer to human disease, but are limited by cost and ethical concerns. Therapies currently being studied for adjunctive therapy in CM include arginine (a donor of nitric oxide), inhaled nitric oxide, and recombinant erythropoietin. The potential benefits and harm of each therapy require close study, as many areas of CM pathogenesis remain unclear. Further studies are required, particularly in human disease, to better understand pathogenesis so that effective adjunctive therapy for this illness can be developed.

Original languageEnglish (US)
Title of host publicationNeuroinflammation and Neurodegeneration
PublisherSpringer New York
Number of pages24
ISBN (Electronic)9781493910717
ISBN (Print)1493910701, 9781493910700
StatePublished - Apr 1 2014
Externally publishedYes


  • Animal
  • Cerebral malaria
  • Experimental
  • Human
  • Inflammation
  • Model
  • Murine
  • Plasmodium falciparum
  • Sequestration

ASJC Scopus subject areas

  • Medicine(all)
  • Neuroscience(all)

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  • Cite this

    Park, G. S., & John, C. C. (2014). Cerebral malaria. In Neuroinflammation and Neurodegeneration (pp. 405-428). Springer New York. https://doi.org/10.1007/978-1-4939-1071-7_19