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      Impaired everyday memory associated with encephalopathy of severe malaria: the role of seizures and hippocampal damage

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          Abstract

          Background

          Seizures are common in children admitted with severe falciparum malaria and are associated with neuro-cognitive impairments. Prolonged febrile seizures are associated with hippocampal damage and impaired memory. It was hypothesized that severe malaria causes impaired everyday memory which may be associated with hippocampal damage.

          Methods

          An everyday memory battery was administered on 152 children with cerebral malaria (CM) (mean age, 7 y 4 months [SD 13 months]; 77 males) 156 children (mean age, 7 y 4 months [SD, 14 months]; 72 males) with malaria plus complex seizures (MS) and 179 children (mean age, 7 y 6 months [SD, 13 months]; 93 males) unexposed to either condition.

          Results

          CM was associated with poorer everyday memory [95% CI, -2.46 to -0.36, p = 0.004] but not MS [95% CI, -0.91 to 1.16, p = 1.00] compared to unexposed children. Children with exposure to CM performed more poorly in recall [95% CI, -0.79 to -0.04, p = 0.024] and recognition subtests [95% CI, -0.90 to -0.17, p = 0.001] but not in prospective memory tests compared to controls. The health factors that predicted impaired everyday memory outcome in children with exposure to CM was profound coma [95% CI, 0.02 to 0.88, p = 0.037] and multiple episodes of hypoglycaemia [95% CI, 0.05 to 0.78, p = 0.020], but not seizures.

          Discussion

          The findings show that exposure to CM was associated with a specific impairment of everyday memory. Seizures commonly observed in severe malaria may not have a causal relationship with poor outcome, but rather be associated with profound coma and repeated metabolic insults (multi-hypoglycaemia) that are strongly associated with impaired everyday memory.

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          Most cited references29

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          The global distribution of clinical episodes of Plasmodium falciparum malaria.

          Interest in mapping the global distribution of malaria is motivated by a need to define populations at risk for appropriate resource allocation and to provide a robust framework for evaluating its global economic impact. Comparison of older and more recent malaria maps shows how the disease has been geographically restricted, but it remains entrenched in poor areas of the world with climates suitable for transmission. Here we provide an empirical approach to estimating the number of clinical events caused by Plasmodium falciparum worldwide, by using a combination of epidemiological, geographical and demographic data. We estimate that there were 515 (range 300-660) million episodes of clinical P. falciparum malaria in 2002. These global estimates are up to 50% higher than those reported by the World Health Organization (WHO) and 200% higher for areas outside Africa, reflecting the WHO's reliance upon passive national reporting for these countries. Without an informed understanding of the cartography of malaria risk, the global extent of clinical disease caused by P. falciparum will continue to be underestimated.
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            Severe falciparum malaria. World Health Organization, Communicable Diseases Cluster.

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              Cerebral malaria in children is associated with long-term cognitive impairment.

              Cerebral malaria affects >785000 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. 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 >or=1 of 3 cognitive areas tested. At 2-year follow-up testing, 26.3% of children with cerebral malaria and 12.5% with uncomplicated malaria had cognitive deficits in >or=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. 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.
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                Author and article information

                Journal
                Malar J
                Malaria Journal
                BioMed Central
                1475-2875
                2009
                1 December 2009
                : 8
                : 273
                Affiliations
                [1 ]The Centre for Geographical Medicine Research (Coast), Kenya Medical Research Institute, Kilifi, Kenya
                [2 ]Centre for International Health and Development, University College London Institute of Child Health, UK
                [3 ]Case Western Reserve University, International Centre for Behavioural Development, USA
                [4 ]Developmental Cognitive Neuroscience Unit, University College London Institute of Child Health, UK
                [5 ]Neurosciences Unit, Institute of Child Health, University College London, London, UK
                [6 ]Department of Paediatrics and Child Health, Mulago Hospital/Makerere University, Kampala, Uganda
                [7 ]Infectious Disease Epidemiology Unit, Department of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, UK
                [8 ]Clinical Research Unit, Infectious Disease Epidemiology Unit, Department of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, UK
                Article
                1475-2875-8-273
                10.1186/1475-2875-8-273
                2794875
                19951424
                f3cd5c84-466a-4cce-8ea0-c5f1f7461bfd
                Copyright ©2009 Kihara et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 16 September 2009
                : 1 December 2009
                Categories
                Research

                Infectious disease & Microbiology
                Infectious disease & Microbiology

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