Volume 97, Issue 1
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645



Cerebral malaria (CM) is a common cause of death and disability among children in sub-Saharan Africa. Many prior studies of neuropsychiatric morbidity have been limited by a cross-sectional design or a short duration of follow-up. Most have included subjects who may have presented with coma due to a disease process other than CM. No studies have assessed the relationship between magnetic resonance imaging (MRI) findings and long-term outcomes. The Cognitive Outcomes and Psychiatric symptoms of retinopathy-positive CM (COPS) cohort is the first large ( = 221) prospectively recruited cohort of stringently defined cases of CM and hospital-based, age-matched, non-CM controls in whom cognitive and psychiatric outcomes are assessed with standardized measures semi-annually for up to 5 years. We report baseline characteristics of the cohort and outcomes at 1 month. At enrollment, CM cases were more likely to come from families with fewer socioeconomic resources and to have health characteristics that increase risk for malaria. In children younger than 5 years, cases were delayed in motor, language, and social development by approximately 6 months, compared with controls. More significant delays occurred in those with MRI abnormalities at the 1-month follow-up visit. There were no differences between cases and controls in inhibitory self-control, nor in cognitive function in children ≥ 5 years of age. The latter finding may be related to the smaller sample size, case-control imbalance in socioeconomic status, or the use of cognitive and behavioral assessments that are less culturally appropriate to this population. Continued follow-up will help determine predictors of long-term outcomes.


Article metrics loading...

Loading full text...

Full text loading...



  1. World Health Organization, 2016. World Malaria Report 2016. Geneva, Switzerland: World Health Organization.
  2. Idro R, Marsh K, John CC, Newton CR, , 2010. Cerebral malaria: mechanisms of brain injury and strategies for improved neurocognitive outcome. Pediatr Res 68: 267274.[Crossref]
  3. Birbeck GL, Molyneux ME, Kaplan PW, Seydel KB, Chimalizeni YF, Kawaza K, Taylor TE, , 2010. Blantyre malaria project epilepsy study (BMPES) of neurological outcomes in retinopathy-positive paediatric cerebral malaria survivors: a prospective cohort study. Lancet Neurol 9: 11731181.[Crossref]
  4. Idro R, Ndiritu M, Ogutu B, Mithwani S, Maitland K, Berkley J, Crawley J, Fegan G, Bauni E, Peshu N, , 2007. Burden, features, and outcome of neurological involvement in acute falciparum malaria in Kenyan children. JAMA 297: 22322240.[Crossref]
  5. World Health Organization, 2014. Severe malaria. Trop Med Int Health 19: 7131.[Crossref]
  6. Boivin MJ, Bangirana P, Byarugaba J, Opoka RO, Idro R, Jurek AM, John CC, , 2007. Cognitive impairment after cerebral malaria in children: a prospective study. Pediatrics 119: e360e366.[Crossref]
  7. John CC, Bangirana P, Byarugaba J, Opoka RO, Idro R, Jurek AM, Wu B, Boivin MJ, , 2008. Cerebral malaria in children is associated with long-term cognitive impairment. Pediatrics 122: e92e99.[Crossref]
  8. Holding PA, Stevenson J, Peshu N, Marsh K, , 1999. Cognitive sequelae of severe malaria with impaired consciousness. Trans R Soc Trop Med Hyg 93: 529534.[Crossref]
  9. Kihara M, Carter JA, Holding PA, Vargha-Khadem F, Scott RC, Idro R, Fegan GW, de Haan M, Neville BG, Newton CR, , 2009. Impaired everyday memory associated with encephalopathy of severe malaria: the role of seizures and hippocampal damage. Malar J 8: 273.[Crossref]
  10. Boivin MJ, Vokhiwa M, Sikorskii A, Magen JG, Beare NA, , 2014. Cerebral malaria retinopathy predictors of persisting neurocognitive outcomes in Malawian children. Pediatr Infect Dis J 33: 821824.[Crossref]
  11. Idro R, Kakooza-Mwesige A, Balyejjussa S, Mirembe G, Mugasha C, Tugumisirize J, Byarugaba J, , 2010. Severe neurological sequelae and behaviour problems after cerebral malaria in Ugandan children. BMC Res Notes 3: 104.[Crossref]
  12. Idro R, Carter JA, Fegan G, Neville BG, Newton CR, , 2006. Risk factors for persisting neurological and cognitive impairments following cerebral malaria. Arch Dis Child 91: 142148.[Crossref]
  13. Bangirana P, Opoka RO, Boivin MJ, Idro R, Hodges JS, Romero RA, Shapiro E, John CC, , 2014. Severe malarial anemia is associated with long-term neurocognitive impairment. Clin Infect Dis 59: 336344.[Crossref]
  14. Bangirana P, Opoka RO, Boivin MJ, Idro R, Hodges JS, John CC, , 2016. Neurocognitive domains affected by cerebral malaria and severe malarial anemia in children. Learn Individ Differ 46: 3844.[Crossref]
  15. Taylor TE, Fu WJ, Carr RA, Whitten RO, Mueller JS, Fosiko NG, Lewallen S, Liomba NG, Molyneux ME, , 2004. Differentiating the pathologies of cerebral malaria by postmortem parasite counts. Nat Med 10: 143145.[Crossref]
  16. Postels DG, Taylor TE, Molyneux M, Mannor K, Kaplan PW, Seydel KB, Chimalizeni YF, Kawaza K, Birbeck GL, , 2012. Neurologic outcomes in retinopathy-negative cerebral malaria survivors. Neurology 79: 12681272.[Crossref]
  17. Seydel KB, Kampondeni SD, Valim C, Potchen MJ, Milner DA, Muwalo FW, Birbeck GL, Bradley WG, Fox LL, Glover SJ, Hammond CA, Heyderman RS, Chilingulo CA, Molyneux ME, Taylor TE, , 2015. Brain swelling and death in children with cerebral malaria. N Engl J Med 372: 11261137.[Crossref]
  18. Gladstone M, Lancaster GA, Umar E, Nyirenda M, Kayira E, van den Broek NR, Smyth RL, , 2010. The Malawi developmental assessment tool (MDAT): the creation, validation, and reliability of a tool to assess child development in rural African settings. PLoS Med 7: e1000273.[Crossref]
  19. Bangirana P, Seggane-Musisi Allebeck P, Giordani B, John CC, Opoka OR, Byarugaba J, Ehnvall A, Boivin MJ, , 2009. A preliminary examination of the construct validity of the KABC-II in Ugandan children with a history of cerebral malaria. Afr Health Sci 9: 186192.
  20. Kaufman AS, , 2004. KABC-II: Kaufman Assessment Battery for Children. Bloomington, MN: NCS Pearson.
  21. Boivin MJ, Gladstone MJ, Vokhiwa M, Birbeck GL, Magen JG, Page C, Semrud-Clikeman M, Kauye F, Taylor TE, , 2011. Developmental outcomes in Malawian children with retinopathy-positive cerebral malaria. Trop Med Int Health 16: 263271.[Crossref]
  22. Gioia GA, Isquith PK, Guy SC, Kenworthy L, , 2000. Behavior Rating Inventory of Executive Function: BRIEF. Odessa, FL: Psychological Assessment Resources.
  23. Familiar I, Ruisenor-Escudero H, Giordani B, Bangirana P, Nakasujja N, Opoka R, Boivin M, , 2015. Use of the behavior rating inventory of executive function and child behavior checklist in Ugandan children with HIV or a history of severe malaria. J Dev Behav Pediatr 36: 277284.[Crossref]
  24. Bangirana P, Musisi S, Boivin MJ, Ehnvall A, John CC, Bergemann TL, Allebeck P, , 2011. Malaria with neurological involvement in Ugandan children: effect on cognitive ability, academic achievement and behaviour. Malar J 10: 334.[Crossref]
  25. Bangirana P, John CC, Idro R, Opoka RO, Byarugaba J, Jurek AM, Boivin MJ, , 2009. Socioeconomic predictors of cognition in Ugandan children: implications for community interventions. PLoS One 4: e7898.[Crossref]
  26. Bergemann TL, Bangirana P, Boivin MJ, Connett JE, Giordani BJ, John CC, , 2012. Statistical approaches to assess the effects of disease on neurocognitive function over time. J Biom Biostat (Suppl 7): 7310.

Data & Media loading...

Supplementary Data

Supplemental Figure

  • Received : 10 Jan 2017
  • Accepted : 28 Feb 2017

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error