Computerized rehabilitation for cognitive deficits after central nervous system malaria in Ugandan children

Background: Malaria infecting the central nervous system (CNS) affects over 575,000 children annually in sub-Saharan Africa leading to cognitive deficits. The effect of this form of malaria on everyday behaviour and academic achievement has not been investigated in Uganda. In addition, no interventions have been carried out for children whose cognitive functioning has been affected by CNS malaria.

Main objective: To investigate the effectiveness of a rehabilitation program for cognitive deficits in Ugandan children after CNS malaria.

Methods: Five studies were carried out (I-V). Study I investigated the long-term cognitive outcomes of CNS malaria. Children were given cognitive assessments 24 months after the malaria episode. In Study II, this same cohort of children were followed up and randomly assigned to receive either computerised cognitive rehabilitation training or treatment as usual, approximately four years after the CNS malaria episode. Pre- and post-intervention cognitive and behavioural assessments were done. The construct validity of a new cognitive test battery, the Kaufman Assessment Battery for Children second edition (KABC-II), was validated in Study III. The effect of CNS malaria on cognition, behaviour and academic achievement was investigated in Study IV. Study V investigated the effect of immediate computerised cognitive rehabilitation training on cognition, behaviour and academic achievement after an episode of CNS malaria. Chi-square and multiple linear regression analyses were used in Study I, analysis of covariance in studies II, IV, V and factor analysis in Study III.

Results: There was a 26.3% prevalence of cognitive impairment two years after CNS malaria with attention most affected. CNS malaria was associated with a 3.67 increased risk for impairment (Study I). At three months assessment, children with malaria had lower attention scores (estimated mean difference = 0.32, 95% confidence interval (CI) = 0.01 to 0.63) and more internalising behavioural problems (0.31, CI, = 0.05 to 0.56) than the community controls (Study IV). Cognitive rehabilitation initiated four years after the illness resulted in improvement in spatial working memory, learning, psychomotor speed and internalising behaviour (Study II) while cognitive rehabilitation initiated three months after the malaria episode improved Learning only (mean difference in adjusted scores between intervention and control groups (standard error), 12.46 (6.05) (Study V). Factor analysis of the KABC-II resulted in five factors measuring Working Memory, Visuospatial skills, Learning and Planning. The fifth factor was composed of items that did not measure a specific cognitive ability (Study III).

Conclusion: Both delayed and immediate computerised cognitive rehabilitation result in improved cognition and behaviour after CNS malaria in Ugandan children.

List of scientific papers

I. 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. 2008, 122(1):e92-99.
https://doi.org/10.1542/peds.2007-3709

II. Bangirana P, Giordani B, John CC, Page C, Opoka RO, Boivin MJ. Immediate Neuropsychological and Behavioral Benefits of Computerized Cognitive Rehabilitation in Ugandan Pediatric Cerebral Malaria Survivors. Journal of Developmental & Behavioral Pediatrics. 2009, 30(4):310-318.
https://doi.org/10.1097/DBP.0b013e3181b0f01b

III. Bangirana P, Musisi S, Allebeck P, Giordani B, John CC, Opoka OR, Byarugaba J, Ehnvall A, Boivin MJ. A preliminary examination of the construct validity of the KABC-II in Ugandan children with a history of cerebral malaria. African Health Sciences. 2009, 9(3):186-192.
https://pubmed.ncbi.nlm.nih.gov/20589149

IV. Bangirana P, Musisi S, Boivin MJ, Ehnvall A, John CC, Allebeck P. Malaria with neurological involvement in Ugandan children: effect on cognitive ability, academic achievement and behaviour. [Manuscript]

V. Bangirana P, Allebeck P, Boivin MJ, John CC, Page C, Ehnvall A, Musisi S. Cognitive rehabilitation in Ugandan children after severe malaria: effects on cognition, academic achievement and behaviour. [Manuscript]