Skip to main content
SpringerLink
Log in

Neurodisability Caused by Malaria: Burden and Pathophysiological Mechanisms

  • Living reference work entry
  • First Online:
Encyclopedia of Malaria

  • 312 Accesses

Synonyms

Neurodisability of malaria

Introduction

Malaria is a leading parasitic disease in tropical countries and a major cause of ill health and death. This entry examines the long-term consequences of the different clinical manifestations of Plasmodium falciparum infection. We estimate the burden and types of neurodisability and propose possible mechanisms by which these may arise.

The Burden and Clinical Manifestations of Malaria

Malaria is recognized as a major cause of death in tropical countries, but its effects on the brain, as a cause of long-term morbidity, are less well publicized. Up to 40 % of the world’s population lives in malaria-endemic areas where they are at risk of contracting the disease. Individuals living in non-endemic areas often get exposed when they visit these endemic areas. Most transmission occurs in sub-Saharan Africa (where the high disease burden is thought to be a contributory factor to the low economic productivity and high levels of poverty) and in...

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

Access this chapter

Log in via an institution

Institutional subscriptions

References

  • Abubakar A, Van De Vijver FJ, Mithwani S, Obiero E, Lewa N, Kenga S, Katana K, Holding P. Assessing developmental outcomes in children from Kilifi, Kenya, following prophylaxis for seizures in cerebral malaria. J Health Psychol. 2007;12:417–30.

    Article  PubMed  Google Scholar 

  • Al Serouri AW, Grantham-McGregor SM, Greenwood B, Costello A. Impact of asymptomatic malaria parasitaemia on cognitive function and school achievement of schoolchildren in the Yemen Republic. Parasitology. 2000;121(Pt 4):337–45.

    Article  PubMed  Google Scholar 

  • Anstey NM, Weinberg JB, Hassanali MY, Mwaikambo ED, Manyenga D, Misukonis MA, Arnelle DR, Hollis D, McDonald MI, Granger DL. Nitric oxide in Tanzanian children with malaria: inverse relationship between malaria severity and nitric oxide production/nitric oxide synthase type 2 expression. J Exp Med. 1996;184:557–67.

    Article  CAS  PubMed  Google Scholar 

  • Bangirana P, Opoka RO, Boivin MJ, Idro R, Hodges JS, Romero RA, Shapiro E, John CC. Severe malarial anemia is associated with long-term neurocognitive impairment. Clin Infect Dis. 2014;59:336–44.

    Article  PubMed Central  PubMed  Google Scholar 

  • Beare NA, Harding SP, Taylor TE, Lewallen S, Molyneux ME. Perfusion abnormalities in children with cerebral malaria and malarial retinopathy. J Infect Dis. 2009;199:263–71.

    Article  PubMed Central  PubMed  Google Scholar 

  • Bernard C, Anderson A, Becker A, Poolos NP, Beck H, Johnston D. Acquired dendritic channelopathy in temporal lobe epilepsy. Science. 2004;305:532–5.

    Article  CAS  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;9:1173–81.

    Article  PubMed Central  PubMed  Google Scholar 

  • Boivin MJ, Gladstone MJ, Vokhiwa M, Birbeck GL, Magen JG, Page C, Semrud-Clikeman M, Kauye F, Taylor TE. Developmental outcomes in Malawian children with retinopathy-positive cerebral malaria. Trop Med Int Health. 2011;16:263–71.

    Article  PubMed Central  PubMed  Google Scholar 

  • Bondi FS. The incidence and outcome of neurological abnormalities in childhood cerebral malaria: a long-term follow-up of 62 survivors. Trans R Soc Trop Med Hyg. 1992;86:17–9.

    Article  CAS  PubMed  Google Scholar 

  • Brewster DR, Kwiatkowski D, White NJ. Neurological sequelae of cerebral malaria in children. Lancet. 1990;336:1039–43.

    Article  CAS  PubMed  Google Scholar 

  • Brown H, Rogerson S, Taylor T, Tembo M, Mwenechanya J, Molyneux M, Turner G. Blood-brain barrier function in cerebral malaria in Malawian children. Am J Trop Med Hyg. 2001;64:207–13.

    CAS  PubMed  Google Scholar 

  • Carter JA, Murira GM, Ross AJ, Mung’ala-Odera V, Newton CR. Speech and language sequelae of severe malaria in Kenyan children. Brain Inj. 2003;17:217–24.

    Article  CAS  PubMed  Google Scholar 

  • Carter JA, Neville BG, White S, Ross AJ, Otieno G, Mturi N, Musumba C, Newton CR. Increased prevalence of epilepsy associated with severe falciparum malaria in children. Epilepsia. 2004;45:978–81.

    Article  PubMed  Google Scholar 

  • Carter JA, Ross AJ, Neville BG, Obiero E, Katana K, Mung’ala-Odera V, Lees JA, Newton CR. Developmental impairments following severe falciparum malaria in children. Trop Med Int Health. 2005a;10:3–10.

    Article  PubMed  Google Scholar 

  • Carter JA, Mung’ala-Odera V, Neville BG, Murira G, Mturi N, Musumba C, Newton CR. Persistent neurocognitive impairments associated with severe falciparum malaria in Kenyan children. J Neurol Neurosurg Psychiatry. 2005b;76:476–81.

    Article  PubMed Central  CAS  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;48:51–7.

    Article  PubMed  Google Scholar 

  • Christensen SS, Eslick GD. Cerebral malaria as a risk factor for the development of epilepsy and other long-term neurological conditions: a meta-analysis. Trans R Soc Trop Med Hyg. 2015;109:233–38.

    Article  PubMed  Google Scholar 

  • Clark IA, Alleva LM. Is human malarial coma caused, or merely deepened, by sequestration? Trends Parasitol. 2009;25:314–8.

    Article  PubMed  Google Scholar 

  • Clavier N, Rahimy C, Falanga P, Ayivi B, Payen D. No evidence for cerebral hypoperfusion during cerebral malaria. Crit Care Med. 1999;27:628–32.

    Article  CAS  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 

  • Cramer JP, Nussler AK, Ehrhardt S, Burkhardt J, Otchwemah RN, Zanger P, Dietz E, Gellert S, Bienzle U, Mockenhaupt FP. Age-dependent effect of plasma nitric oxide on parasite density in Ghanaian children with severe malaria. Trop Med Int Health. 2005;10:672–80.

    Article  CAS  PubMed  Google Scholar 

  • Crawley J, Smith S, Kirkham F, Muthinji P, Waruiru C, Marsh K. Seizures and status epilepticus in childhood cerebral malaria. QJM. 1996;89:591–7.

    Article  CAS  PubMed  Google Scholar 

  • Crawley J, Waruiru C, Mithwani S, Mwangi I, Watkins W, Ouma D, Winstanley P, Peto T, Marsh K. Effect of phenobarbital on seizure frequency and mortality in childhood cerebral malaria: a randomised, controlled intervention study. Lancet. 2000;355:701–6.

    Article  CAS  PubMed  Google Scholar 

  • Di Perri G, Di Perri IG, Monteiro GB, Bonora S, Hennig C, Cassatella M, Micciolo R, Vento S, Dusi S, Bassetti D, et al. Pentoxifylline as a supportive agent in the treatment of cerebral malaria in children. J Infect Dis. 1995;171:1317–22.

    Article  PubMed  Google Scholar 

  • Dichter MA. Emerging concepts in the pathogenesis of epilepsy and epileptogenesis. Arch Neurol. 2009;66:443–7.

    Article  PubMed  Google Scholar 

  • Dobbie M, Crawley J, Waruiru C, Marsh K, Surtees R. Cerebrospinal fluid studies in children with cerebral malaria: an excitotoxic mechanism? Am J Trop Med Hyg. 2000;62:284–90.

    CAS  PubMed  Google Scholar 

  • Dondorp AM, Nyanoti M, Kager PA, Mithwani S, Vreeken J, Marsh K. The role of reduced red cell deformability in the pathogenesis of severe falciparum malaria and its restoration by blood transfusion. Trans R Soc Trop Med Hyg. 2002;96:282–6.

    Article  CAS  PubMed  Google Scholar 

  • Factsheet on the world malaria report 2014. http://www.who.int/malaria/media/world_malaria_report_2014/en/

  • Fernando D, Wickremasinghe R, Mendis KN, Wickremasinghe AR. Cognitive performance at school entry of children living in malaria-endemic areas of Sri Lanka. Trans R Soc Trop Med Hyg. 2003a;97:161–5.

    Article  PubMed  Google Scholar 

  • Fernando SD, Gunawardena DM, Bandara MR, De Silva D, Carter R, Mendis KN, Wickremasinghe AR. The impact of repeated malaria attacks on the school performance of children. Am J Trop Med Hyg. 2003b;69:582–8.

    CAS  PubMed  Google Scholar 

  • Fernando D, de Silva D, Carter R, Mendis KN, Wickremasinghe R. A randomized, double-blind, placebo-controlled, clinical trial of the impact of malaria prevention on the educational attainment of school children. Am J Trop Med Hyg. 2006;74:386–93.

    PubMed  Google Scholar 

  • Halliday KE, Karanja P, Turner EL, Okello G, Njagi K, Dubeck MM, Allen E, Jukes MC, Brooker SJ. Plasmodium falciparum, anaemia and cognitive and educational performance among school children in an area of moderate malaria transmission: baseline results of a cluster randomized trial on the coast of Kenya. Trop Med Int Health. 2012;17:532–49.

    Article  PubMed Central  PubMed  Google Scholar 

  • Holding PA, Stevenson J, Peshu N, Marsh K. Cognitive sequelae of severe malaria with impaired consciousness. Trans R Soc Trop Med Hyg. 1999;93:529–34.

    Article  CAS  PubMed  Google Scholar 

  • Holtkamp M, Schuchmann S, Gottschalk S, Meierkord H. Recurrent seizures do not cause hippocampal damage. J Neurol. 2004;251:458–63.

    Article  PubMed  Google Scholar 

  • Hunt NH, Grau GE. Cytokines: accelerators and brakes in the pathogenesis of cerebral malaria. Trends Immunol. 2003;24:491–9.

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  • Idro R, Maling S, Byarugaba J. Compulsive behavior and coprolalia after cerebral malaria. J Pediatr Neurol. 2005b;3:107–8.

    Google Scholar 

  • Idro R, Carter JA, Fegan G, Neville BG, Newton CR. Risk factors for persisting neurological and cognitive impairments following cerebral malaria. Arch Dis Child. 2006;91:142–8.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Idro R, Ndiritu M, Ogutu B, Mithwani S, Maitland K, Berkley J, Crawley J, Fegan G, Bauni E, Peshu N, et al. Burden, features, and outcome of neurological involvement in acute falciparum malaria in Kenyan children. JAMA. 2007;297:2232–40.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Idro R, Kakooza-Mwesige A, Balyejjussa S, Mirembe G, Mugasha C, Tugumisirize J, Byarugaba J. Severe neurological sequelae and behaviour problems after cerebral malaria in Ugandan children. BMC Res Notes. 2010;3:104.

    Article  PubMed Central  PubMed  Google Scholar 

  • John CC, Opika-Opoka R, Byarugaba J, Idro R, Boivin MJ. Low levels of RANTES are associated with mortality in children with cerebral malaria. J Infect Dis. 2006;194:837–45.

    Article  PubMed  Google Scholar 

  • John CC, Bangirana P, Byarugaba J, Opoka RO, Idro R, Jurek AM, Wu B, Boivin MJ. Cerebral malaria in children is associated with long-term cognitive impairment. Pediatrics. 2008a;122:e92–9.

    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. 2008b;78:198–205.

    PubMed Central  CAS  PubMed  Google Scholar 

  • Kampondeni SD, Potchen MJ, Beare NA, Seydel KB, Glover SJ, Taylor TE, Birbeck GL. MRI findings in a cohort of brain injured survivors of pediatric cerebral malaria. Am J Trop Med Hyg. 2013;88:542–6.

    Article  PubMed Central  PubMed  Google Scholar 

  • Kihara M, Carter JA, Holding P, Vargha-Khadem F, Scott RC, Idro R, Fegan G, de Haan M, Neville BGR, Newton CRJC. Impaired everyday memory associated with encephalopathy of severe malaria: the role of seizures and hippocampal damage. Malar J. 2009;8:273.

    Article  PubMed Central  PubMed  Google Scholar 

  • Lochhead J, Movaffaghy A, Falsini B, Harding S, Riva C, Molyneux M. The effects of hypoxia on the ERG in paediatric cerebral malaria. Eye. 2009. doi:10.1038/eye.2009.162.

    Google Scholar 

  • Looareesuwan S, Wilairatana P, Vannaphan S, Wanaratana V, Wenisch C, Aikawa M, Brittenham G, Graninger W, Wernsdorfer WH. Pentoxifylline as an ancillary treatment for severe falciparum malaria in Thailand. Am J Trop Med Hyg. 1998;58:348–53.

    CAS  PubMed  Google Scholar 

  • Lovegrove FE, Tangpukdee N, Opoka RO, Lafferty EI, Rajwans N, Hawkes M, Krudsood S, Looareesuwan S, John CC, Liles WC, Kain KC. Serum angiopoietin-1 and -2 levels discriminate cerebral malaria from uncomplicated malaria and predict clinical outcome in African children. PLoS One. 2009;4:e4912.

    Article  PubMed Central  PubMed  Google Scholar 

  • Marsh K, Forster D, Waruiru C, Mwangi I, Winstanley M, Marsh V, Newton C, Winstanley P, Warn P, Peshu N, et al. Indicators of life-threatening malaria in African children. N Engl J Med. 1995;332:1399–404.

    Article  CAS  PubMed  Google Scholar 

  • Medana IM, Hien TT, Day NP, Phu NH, Mai NT, Chu’ong LV, Chau TT, Taylor A, Salahifar H, Stocker R, et al. The clinical significance of cerebrospinal fluid levels of kynurenine pathway metabolites and lactate in severe malaria. J Infect Dis. 2002;185:650–6.

    Article  CAS  PubMed  Google Scholar 

  • Medana IM, Idro R, Newton CR. Axonal and astrocyte injury markers in the cerebrospinal fluid of Kenyan children with severe malaria. J Neurol Sci. 2007;258:93–8.

    Article  PubMed  Google Scholar 

  • Nankabirwa J, Wandera B, Kiwanuka N, Staedke SG, Kamya MR, Brooker SJ. Asymptomatic Plasmodium infection and cognition among primary schoolchildren in a high malaria transmission setting in Uganda. Am J Trop Med Hyg. 2013;88:1102–8.

    Article  PubMed Central  PubMed  Google Scholar 

  • Newbold C, Craig A, Kyes S, Rowe A, Fernandez-Reyes D, Fagan T. Cytoadherence, pathogenesis and the infected red cell surface in Plasmodium falciparum. Int J Parasitol. 1999;29:927–37.

    Article  CAS  PubMed  Google Scholar 

  • Newton CR, Peshu N, Kendall B, Kirkham FJ, Sowunmi A, Waruiru C, Mwangi I, Murphy SA, Marsh K. Brain swelling and ischaemia in Kenyans with cerebral malaria. Arch Dis Child. 1994;70:281–7.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Newton CR, Marsh K, Peshu N, Kirkham FJ. Perturbations of cerebral hemodynamics in Kenyans with cerebral malaria. Pediatr Neurol. 1996;15:41–9.

    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;76:219–26.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Ngoungou EB, Preux PM. Cerebral malaria and epilepsy. Epilepsia. 2008;49:19–24.

    Article  PubMed  Google Scholar 

  • Ngoungou EB, Koko J, Druet-Cabanac M, Assengone-Zeh-Nguema Y, Launay MN, Engohang E, Moubeka-Mounguengui M, Kouna-Ndouongo P, Loembe PM, Preux PM, Kombila M. Cerebral malaria and sequelar epilepsy: first matched case-control study in Gabon. Epilepsia. 2006;47:2147–53.

    Article  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;348:917–21.

    Article  CAS  PubMed  Google Scholar 

  • Nyarango PM, Gebremeskel T, Mebrahtu G, Mufunda J, Abdulmumini U, Ogbamariam A, Kosia A, Gebremichael A, Gunawardena D, Ghebrat Y, Okbaldet Y. A steep decline of malaria morbidity and mortality trends in Eritrea between 2000 and 2004: the effect of combination of control methods. Malar J. 2006;5:33.

    Article  PubMed Central  PubMed  Google Scholar 

  • Okiro EA, Hay SI, Gikandi PW, Sharif SK, Noor AM, Peshu N, Marsh K, Snow RW. The decline in paediatric malaria admissions on the coast of Kenya. Malar J. 2007;6:151.

    Article  PubMed Central  PubMed  Google Scholar 

  • Opoka RO, Bangirana P, Boivin MJ, John CC, Byarugaba J. Seizure activity and neurological sequelae in Ugandan children who have survived an episode of cerebral malaria. Afr Health Sci. 2009;9:75–81.

    PubMed Central  PubMed  Google Scholar 

  • Potchen MJ, Birbeck GL, Demarco JK, Kampondeni SD, Beare N, Molyneux ME, Taylor TE. Neuroimaging findings in children with retinopathy-confirmed cerebral malaria. Eur J Radiol. 2010;74:262–8.

    Article  PubMed Central  PubMed  Google Scholar 

  • Scott RC, King MD, Gadian DG, Neville BG, Connelly A. Hippocampal abnormalities after prolonged febrile convulsion: a longitudinal MRI study. Brain. 2003;126:2551–7.

    Article  PubMed  Google Scholar 

  • Snow RW, Guerra CA, Noor AM, Myint HY, Hay SI. The global distribution of clinical episodes of Plasmodium falciparum malaria. Nature. 2005;434:214–7.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Sokol DK, Demyer WE, Edwards-Brown M, Sanders S, Garg B. From swelling to sclerosis: acute change in mesial hippocampus after prolonged febrile seizure. Seizure. 2003;12:237–40.

    Article  PubMed  Google Scholar 

  • Temkin NR. Antiepileptogenesis and seizure prevention trials with antiepileptic drugs: meta-analysis of controlled trials. Epilepsia. 2001;42:515–24.

    Article  CAS  PubMed  Google Scholar 

  • van Hensbroek MB, Palmer A, Onyiorah E, Schneider G, Jaffar S, Dolan G, Memming H, Frenkel J, Enwere G, Bennett S, et al. The effect of a monoclonal antibody to tumor necrosis factor on survival from childhood cerebral malaria. J Infect Dis. 1996;174:1091–7.

    Article  PubMed  Google Scholar 

  • van Hensbroek MB, Palmer A, Jaffar S, Schneider G, Kwiatkowski D. Residual neurologic sequelae after childhood cerebral malaria. J Pediatr. 1997;131:125–9.

    Article  PubMed  Google Scholar 

  • Verity CM. Do seizures damage the brain? The epidemiological evidence. Arch Dis Child. 1998;78:78–84.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Walker O, Salako LA, Sowunmi A, Thomas JO, Sodeine O, Bondi FS. Prognostic risk factors and post mortem findings in cerebral malaria in children. Trans R Soc Trop Med Hyg. 1992;86:491–3.

    Article  CAS  PubMed  Google Scholar 

  • Zucker JR, Lackritz EM, Ruebush 2nd TK, Hightower AW, Adungosi JE, Were JB, Metchock B, Patrick E, Campbell CC. Childhood mortality during and after hospitalization in western Kenya: effect of malaria treatment regimens. Am J Trop Med Hyg. 1996;55:655–60.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Paediatrics and Child Health, Mulago Hospital/Makerere University College of Health Sciences, Kampala, Uganda

    Richard Idro

  2. Nuffield Department of Medicine, Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, UK

    Richard Idro

  3. Kenya Medical Research Institute and the Wellcome Trust Centre for Geographic Medicine Research – Coast, Kilifi, Kenya

    Charles R. J. C. Newton

  4. Department of Psychiatry, University of Oxford, Oxford, UK

    Charles R. J. C. Newton

Authors
  1. Richard Idro
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Charles R. J. C. Newton
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Richard Idro .

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

© 2015 Springer Science+Business Media New York

About this entry

Cite this entry

Idro, R., Newton, C.R.J.C. (2015). Neurodisability Caused by Malaria: Burden and Pathophysiological Mechanisms. In: Hommel, M., Kremsner, P. (eds) Encyclopedia of Malaria. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-8757-9_116-1

Download citation

  • DOI: https://doi.org/10.1007/978-1-4614-8757-9_116-1

  • 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