Skip to main content
SpringerLink
Log in
Book cover

Encyclopedia of Malaria pp 1–10Cite as

Cerebral Malaria: Pathophysiology of Clinical Features

  • Living reference work entry
  • First Online:

  • 393 Accesses

Synonyms

Malaria comatose; Malarial coma

Definition, Epidemiology, and Clinical Features of Cerebral Malaria

The conventional World Health Organization (WHO) definition of cerebral malaria (CM) comprises unrousable or deep coma in a patient with asexual forms of malaria parasites in the peripheral blood where there is no other apparent cause for altered consciousness (WHO 2000). It is also known as malarial coma or malaria comatosa.

Of the estimated 500 million clinical episodes of malaria that occur globally each year, 1–4 % of patients will develop severe disease and 10 % of these will have CM (Idro et al. 2005). Most CM occurs in young sub-Saharan African children, but it is a well recognized albeit less frequent complication in adults. The case fatality rate for pediatric CM varies by geographical region but has remained at approximately 20 %, while a further 5–10 % of children are left with neurological sequelae that range from mild and transient abnormalities to profound and...

This is a preview of subscription content, log in via an institution.

References

  • Bergmark B, Bergmark R, Beaudrap PD, Boum Y, Mwanga-Amumpaire J, Carroll R, Zapol W. Inhaled nitric oxide and cerebral malaria: basis of a strategy for buying time for pharmacotherapy. Pediatr Infect Dis J. 2012;31(12):e250–4.

    Article  PubMed  Google Scholar 

  • Birbeck GL, Molyneux ME, Kaplan PW, Seydel KB, Chimalizeni YF, Kawaza K, Taylor TE. Blantyre Malaria Project Epilepsy Study (BMPES) of neurological outcomes in retinopathy-positive paediatric cerebral malaria survivors: a prospective cohort study. Lancet Neurol. 2010;9(12):1173–81.

    Article  PubMed Central  PubMed  Google Scholar 

  • Carter JA, Lees JA, Gona JK, Murira G, Rimba K, Neville BG, Newton CR. Severe falciparum malaria and acquired childhood language disorder. Dev Med Child Neurol. 2006;48(1):51–7.

    Article  PubMed  Google Scholar 

  • Cox-Singh J, Hiu J, Lucas SB, Divis PC, Zulkarnaen M, Chandran P, Wong KT, Adem P, Zaki SR, Singh B, Krishna S. Severe malaria – a case of fatal Plasmodium knowlesi infection with post-mortem findings: a case report. Malar J. 2010;9:10.

    Article  PubMed Central  PubMed  Google Scholar 

  • Craig AG, Khairul MF, Patil PR. Cytoadherence and severe malaria. Malays J Med Sci. 2012;19(2):5–18.

    PubMed  Google Scholar 

  • Davis TM, Suputtamongkol Y, Spencer JL, Ford S, Chienkul N, Schulenburg WE, White NJ. Measures of capillary permeability in acute falciparum malaria: relation to severity of infection and treatment. Clin Infect Dis. 1992;15(2):256–66.

    Article  CAS  PubMed  Google Scholar 

  • de Silva HJ, Hoang P, Dalton H, de Silva NR, Jewell DP, Peiris JB. Immune activation during cerebellar dysfunction following Plasmodium falciparum malaria. Trans R Soc Trop Med Hyg. 1992;86(2):129–31.

    Article  PubMed  Google Scholar 

  • Debierre-Grockiego F, Schwarz RT. Immunological reactions in response to apicomplexan glycosylphosphatidylinositols. Glycobiology. 2010;20(7):801–11.

    Article  CAS  PubMed  Google Scholar 

  • Dorovini-Zis K, Schmidt K, Huynh H, Fu W, Whitten RO, Milner D, Kamiza S, Molyneux M, Taylor TE. The neuropathology of fatal cerebral malaria in malawian children. Am J Pathol. 2011;178(5):2146–58.

    Article  PubMed Central  PubMed  Google Scholar 

  • Erdman LK, Dhabangi A, Musoke C, Conroy AL, Hawkes M, Higgins S, Rajwans N, Wolofsky KT, Streiner DL, Liles WC, Cserti-Gazdewich CM, Kain KC. Combinations of host biomarkers predict mortality among Ugandan children with severe malaria: a retrospective case–control study. PLoS One. 2011;6(2):e17440.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Idro R, Jenkins NE, Newton CR. Pathogenesis, clinical features, and neurological outcome of cerebral malaria. Lancet Neurol. 2005;4(12):827–40.

    Article  PubMed  Google Scholar 

  • Idro R, Marsh K, John CC, Newton CR. Cerebral malaria: mechanisms of brain injury and strategies for improved neurocognitive outcome. Pediatr Res. 2010;68(4):267–74.

    Article  PubMed Central  PubMed  Google Scholar 

  • John CC, Panoskaltsis-Mortari A, Opoka RO, Park GS, Orchard PJ, Jurek AM, Idro R, Byarugaba J, Boivin MJ. Cerebrospinal fluid cytokine levels and cognitive impairment in cerebral malaria. Am J Trop Med Hyg. 2008;78(2):198–205.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Krishna S. Adjunctive management of malaria. Curr Opin Infect Dis. 2012;25(5):484–8.

    Article  PubMed  Google Scholar 

  • Makani J, Matuja W, Liyombo E, Snow RW, Marsh K, Warrell DA. Admission diagnosis of cerebral malaria in adults in an endemic area of Tanzania: implications and clinical description. QJM. 2003;96(5):355–62.

    Article  CAS  PubMed  Google Scholar 

  • Manning L, Davis TM. The mechanistic, diagnostic and prognostic utility of biomarkers in severe malaria. Biomark Med. 2013;7(3):363–80.

    Article  CAS  PubMed  Google Scholar 

  • Manning L, Rosanas-Urgell A, Laman M, Edoni H, McLean C, Mueller I, Siba P, Davis TM. A histopathologic study of fatal paediatric cerebral malaria caused by mixed Plasmodium falciparum/Plasmodium vivax infections. Malar J. 2012;11:107.

    Article  PubMed Central  PubMed  Google Scholar 

  • Manning L, Laman M, Davis WA, Davis TME. Clinical features and outcome in children with severe Plasmodium falciparum malaria: a meta-analysis. PLoS One. 2014;9(2):e86737.

    Article  PubMed Central  PubMed  Google Scholar 

  • Maude RJ, Dondorp AM, Abu Sayeed A, Day NP, White NJ, Beare NA. The eye in cerebral malaria: what can it teach us? Trans R Soc Trop Med Hyg. 2009;103(7):661–4.

    Article  PubMed Central  PubMed  Google Scholar 

  • Medana IM, Day NP, Hien TT, Mai NT, Bethell D, Phu NH, Farrar J, Esiri MM, White NJ, Turner GD. Axonal injury in cerebral malaria. Am J Pathol. 2002;160(2):655–66.

    Article  PubMed Central  PubMed  Google Scholar 

  • Medana IM, Day NP, Sachanonta N, Mai NT, Dondorp AM, Pongponratn E, Hien TT, White NJ, Turner GD. Coma in fatal adult human malaria is not caused by cerebral oedema. Malar J. 2011;10:267.

    Article  PubMed Central  PubMed  Google Scholar 

  • Miller LH, Ackerman HC, Su XZ, Wellems TE. Malaria biology and disease pathogenesis: insights for new treatments. Nat Med. 2013;19(2):156–67.

    Article  CAS  PubMed  Google Scholar 

  • Molyneux ME, Taylor TE, Wirima JJ, Borgstein A. Clinical features and prognostic indicators in paediatric cerebral malaria: a study of 131 comatose Malawian children. Q J Med. 1989;71(265):441–59.

    CAS  PubMed  Google Scholar 

  • Newton CR, Krishna S. Severe falciparum malaria in children: current understanding of pathophysiology and supportive treatment. Pharmacol Ther. 1998;79(1):1–53.

    Article  CAS  PubMed  Google Scholar 

  • Newton CR, Crawley J, Sowumni A, Waruiru C, Mwangi I, English M, Murphy S, Winstanley PA, Marsh K, Kirkham FJ. Intracranial hypertension in Africans with cerebral malaria. Arch Dis Child. 1997;76(3):219–26.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Nguyen TH, Day NP, Ly VC, Waller D, Mai NT, Bethell DB, Tran TH, White NJ. Post-malaria neurological syndrome. Lancet. 1996;348(9032):917–21.

    Article  CAS  PubMed  Google Scholar 

  • Pasmanik D. Uber malariapsychosen. Wien Med Wschr. 1897;47:518.

    Google Scholar 

  • Planche T, Macallan DC, Sobande T, Borrmann S, Kun JF, Krishna S, Kremsner PG. Nitric oxide generation in children with malaria and the NOS2G-954C promoter polymorphism. Am J Physiol Regul Integr Comp Physiol. 2010;299(5):R1248–53.

    Article  CAS  PubMed  Google Scholar 

  • Pongponratn E, Turner GD, Day NP, Phu NH, Simpson JA, Stepniewska K, Mai NT, Viriyavejakul P, Looareesuwan S, Hien TT, Ferguson DJ, White NJ. An ultrastructural study of the brain in fatal Plasmodium falciparum malaria. Am J Trop Med Hyg. 2003;69(4):345–59.

    PubMed  Google Scholar 

  • Prapansilp P, Medana I, Mai NT, Day NP, Phu NH, Yeo TW, Hien TT, White NJ, Anstey NM, Turner GD. A clinicopathological correlation of the expression of the angiopoietin-Tie-2 receptor pathway in the brain of adults with Plasmodium falciparum malaria. Malar J. 2013;12:50.

    Article  PubMed Central  PubMed  Google Scholar 

  • Prato M, D’Alessandro S, Van den Steen PE, Opdenakker G, Arese P, Taramelli D, Basilico N. Natural haemozoin modulates matrix metalloproteinases and induces morphological changes in human microvascular endothelium. Cell Microbiol. 2011;13(8):1275–85.

    Article  CAS  PubMed  Google Scholar 

  • Renia L, Howland SW, Claser C, Charlotte Gruner A, Suwanarusk R, Hui Teo T, Russell B, Ng LF. Cerebral malaria: mysteries at the blood–brain barrier. Virulence. 2012;3(2):193–201.

    Article  PubMed Central  PubMed  Google Scholar 

  • Shikani HJ, Freeman BD, Lisanti MP, Weiss LM, Tanowitz HB, Desruisseaux MS. Cerebral malaria: we have come a long way. Am J Pathol. 2012;181(5):1484–92.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Taylor TE, Fu WJ, Carr RA, Whitten RO, Mueller JS, Fosiko NG, Lewallen S, Liomba NG, Molyneux ME. Differentiating the pathologies of cerebral malaria by postmortem parasite counts. Nat Med. 2004;10(2):143–5.

    Article  CAS  PubMed  Google Scholar 

  • Warrell DA. Cerebral malaria: clinical features, pathophysiology and treatment. Ann Trop Med Parasitol. 1997;91(7):875–84.

    Article  CAS  PubMed  Google Scholar 

  • Warrell DA, White NJ, Veall N, Looareesuwan S, Chanthavanich P, Phillips RE, Karbwang J, Pongpaew P, Krishna S. Cerebral anaerobic glycolysis and reduced cerebral oxygen transport in human cerebral malaria. Lancet. 1988;2(8610):534–8.

    Article  CAS  PubMed  Google Scholar 

  • White NJ, Turner GD, Medana IM, Dondorp AM, Day NP. The murine cerebral malaria phenomenon. Trends Parasitol. 2010;26(1):11–5.

    Article  PubMed Central  PubMed  Google Scholar 

  • White NJ, Turner GD, Day NP, Dondorp AM. Lethal malaria: Marchiafava and Bignami were right. J Infect Dis. 2013;208(2):192–8.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Wong RP, Flematti GR, Davis TM. Investigation of volatile organic biomarkers derived from Plasmodium falciparum in vitro. Malar J. 2012;11:314.

    Article  PubMed Central  PubMed  Google Scholar 

  • World Health Organization, Communicable Diseases Cluster. Severe falciparum malaria. Trans R Soc Trop Med Hyg. 2000;94 Suppl 1:S1–90.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. School of Medicine and Pharmacology, Fremantle Hospital, University of Western Australia, Fremantle, WA, Australia

    Timothy M. E. Davis, Moses Laman & Laurens Manning

  2. Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea

    Moses Laman

Authors
  1. Timothy M. E. Davis
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Moses Laman
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Laurens Manning
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Timothy M. E. Davis .

Editor information

Editors and Affiliations

  1. Heswall, United Kingdom

    Marcel Hommel

  2. Institut für Tropenmedizin, Universität Tübingen, Tübingen, Germany

    Peter G. Kremsner

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer Science+Business Media New York

About this entry

Cite this entry

Davis, T.M.E., Laman, M., Manning, L. (2014). Cerebral Malaria: Pathophysiology of Clinical Features. In: Hommel, M., Kremsner, P. (eds) Encyclopedia of Malaria. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-8757-9_99-1

Download citation

  • DOI: https://doi.org/10.1007/978-1-4614-8757-9_99-1

  • Received:

  • Accepted:

  • Published:

  • Publisher Name: Springer, New York, NY

  • Online ISBN: 978-1-4614-8757-9

  • eBook Packages: Springer Reference MedicineReference Module Medicine

Publish with us

Policies and ethics

Search

Navigation