DESCRIPTION (provided by applicant): Research Topic: We have documented in our prior work in Uganda that 1 out of 4 school-age survivors of cerebral malaria (CM) has persisting attention, memory, or learning impairment two years after illness. No viable treatment presently exists to prevent these disabilities, and hundreds of thousands of children are affected each year in sub-Sahara Africa. One hundred and fifty severe malaria survivors (5 to 12 yrs of age), and 150 healthy community control (CC) children recruited from their households will be our study participants. Fifty of these children will be randomly selected to receive 24 training sessions of a computerized cognitive rehabilitation therapy (CCRT) program called Captain's Log, marketed mostly for American children with attention and/or learning problems. A locked version of Captain's Log which does not direct the child's training in a progressive manner will be administered to an active control group, and no intervention for the passive control group. Children will undergo training in their homes or in a nearby clinic supervised by a field trainer. Study Aim 1: To evaluate the effectiveness of CCRT in improving neuropsychological performance and psychiatric outcomes in Ugandan children who survive severe malaria. Study Aim 2: To evaluate whether severity of malaria illness (e.g., immunological brain inflammation, EEG abnormalities) is predictive of neuropsychological benefit from CCRT. Outcome Assessments: The Kaufman Assessment Battery for Children, 2nd ed. (KABC-2), visual and auditory Tests of Variables of Attention (TOVA), CogState computerized neuropsychological screening test, Bruininks-Oseretsky Test of Motor Proficiency (2nd edition), and Achenbach Child Behavior Checklist (CBCL) will be administered before and after the 8-week training period and at 1-yr follow-up. Improvements in academic performance will also be evaluated. We have previously used all these assessments with Ugandan children surviving CM or with HIV to effectively evaluate neuropsychological and psychiatric problems, and to document the effectiveness of CCRT. Captain's Log has an internal evaluator feature which will help us monitor the specific training tasks to which the children best respond. Based on our prior research with CCRT intervention with CM survivors and in children with HIV, we expect CCRT to be effective in improving attention, memory, and learning; and that our assessments will be sensitive enough to document neuropsychological and psychiatric benefit. Analyses: We will compare neuropsychological and psychiatric gains over the 8-weeks of CCRT and at 1-yr follow-up for our intervention groups across the severe malaria and control children (3 by 2 ANCOVA controlling for quality of home environment). These gains will be significantly greater for the CCRT intervention children (Study Aim 1). More severe immunological and EEG indicators during malaria illness will show greater need for an improvement from CCRT (Study Aim 2). Conclusion: CCRT will prove effective and sustainable in rehabilitation for severe malaria. CCRT and computerized cognitive tests will prove viable for treating children in resource-poor settings.

Severe malaria is the single greatest cause of mortality and morbidity in African children less than 5 yrs and malarial illness as a leading cause of neurodisability leaves 1 in 4 survivors with cognitive impairment at some level. Therefore, severe malaria as a disease provides a rich source of attention and working memory impairment upon which to evaluate computerized cognitive rehabilitation training (CCRT) programs specifically designed and prescribed to treat these needs in American children. Furthermore, our CCRT clinical study has overarching scientific value in allowing us to differentiate cognitive performance domains more proximal to CNS disease and amenable to CCRT treatment, from the more pervasive and distal brain/behavior developmental effects of impoverishment in general.