OBJECTIVE-Cerebral malaria affects >785 000 African children every year. We previously documented an increased frequency of cognitive impairment in children with cerebral malaria 6 months after their initial malaria episode. This study was conducted to determine the long-term effects of cerebral malaria on the cognitive function of these children.METHODS-Children who were 5 to 12 years of age and presented to Mulago Hospital, Kampala, Uganda, with cerebral malaria (n = 44) or uncomplicated malaria (n = 54), along with healthy, asymptomatic community children (n = 89), were enrolled in a prospective cohort study of cognition. Cognitive testing was performed at enrollment and 2 years later. The primary outcome was presence of a deficit in ≥1 of 3 cognitive areas tested.RESULTS-At 2-year follow-up testing, 26.3% of children with cerebral malaria and 12.5% with uncomplicated malaria had cognitive deficits in ≥1 area, as compared with 7.6% of community children. Deficits in children with cerebral malaria were primarily in the area of attention (cerebral malaria, 18.4%, vs community children, 2.5%). After adjustment for age, gender, nutrition, home environment, and school level, children with cerebral malaria had a 3.67-fold increased risk for a cognitive deficit compared with community children. Cognitive impairment at 2-year follow-up was associated with hyporeflexia on admission and neurologic deficits 3 months after discharge.CONCLUSIONS-Cerebral malaria is associated with long-term cognitive impairments in 1 of 4 child survivors. Future studies should investigate the mechanisms involved so as to develop interventions aimed at prevention and rehabilitation. NIH Public Access Author ManuscriptPediatrics. Author manuscript; available in PMC 2009 July 1. Published in final edited form as:Pediatrics. What's Known on This SubjectRetrospective studies have suggested that cerebral malaria in children is associated with long-term cognitive deficits. What This Study AddsThis is the first prospective study to document long-term cognitive impairment in children with cerebral malaria. We document that deficits found early persist long-term, whereas additional new deficits are discovered on long-term follow-up.Cerebral Malaria (CM), which is estimated to affect 785 000 children who are younger than 9 years in sub-Saharan Africa every year, 1 is among the deadliest forms of malaria, with an average mortality rate estimated at 18.6%. 2 Gross neurologic deficits are frequent at the time of discharge but generally resolve within 6 months of discharge. 3 A number of retrospective studies have suggested that CM is associated with higher frequencies of more subtle cognitive deficits as long as 3 to 9 years after the episode of CM, 4-8 but, to date, no long-term prospective studies of cognitive impairment after CM have been performed. In retrospective studies, the effects of variables such as home environment or nutrition, which may be important in cognitive development and which may change over time, cannot be assessed in c...

OBJECTIVE-This study was conducted to assess prospectively the frequency of cognitive deficits in children with cerebral malaria.METHODS-Cognitive testing in the areas of working memory, attention, and learning was performed for Ugandan children 5 to 12 years of age with cerebral malaria (n = 44), children with uncomplicated malaria (n = 54), and healthy community children (n = 89) at admission and 3 and 6 months later.RESULTS-Six months after discharge, 21.4% of children with cerebral malaria had cognitive deficits, compared with 5.8% of community children. Deficits were seen in the areas of working memory (11.9% vs 2.3%) and attention (16.7% vs 2.3%). Children with cerebral malaria had a 3.7-fold increased risk of a cognitive deficit, compared with community children, after adjustment for age, gender, nutritional status, school level, and home environment. Among children with cerebral malaria, those with a cognitive deficit had more seizures before admission (mean: 4.1 vs 2.2) and a longer duration of coma (43.6 vs 30.5 hours), compared with those without a deficit. Children with uncomplicated malaria did not have an increased frequency of cognitive deficits.CONCLUSIONS-Cerebral malaria may be a major cause of cognitive impairment in children in sub-Saharan Africa. Cognitive deficits in children with cerebral malaria are more likely for those who have multiple seizures before effective treatment for cerebral malaria. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptIt has been estimated that each year 575 000 children suffer from cerebral malaria (CM) in sub-Saharan Africa. 1 CM is among the deadliest complications of malaria, with an estimated mortality rate in sub-Saharan Africa of 18.6% among hospitalized children. 2 Neurologic deficits are seen frequently at the time of hospital discharge for children with CM, but most resolve within 6 months after discharge. 3 However, several retrospective studies suggested that cognitive deficits in children with CM are more frequent (occurring in 11%-28% of children with CM) and persist for a far longer time (3-9 years after the CM episode) than neurologic deficits. [4][5][6][7][8] The data from those studies were strong and generally consistent, but one study found no evidence of increased cognitive deficits. 9 Furthermore, the original clinical and social assessments of those children were performed as part of studies investigating other aspects of CM and not as part of a study designed specifically to address the question of cognitive deficits in children with CM. Initial cognitive testing was performed for case and control subjects several years after the episode of CM. History, physical examination, and laboratory data were limited to those collected from medical charts, and data on potential confounding risk factors for cognitive deficits, such as home environment and level of schooling at the time of enrollment, either were not collected or were collected through questionnaires and therefore were subject to significant recall bia...

Buccal midazolam was as safe as and more effective than rectal diazepam for the treatment of seizures in Ugandan children, although benefits were limited to children without malaria.