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      The 'hidden' burden of malaria: cognitive impairment following infection

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      1 , , 2 , 3
      Malaria Journal
      BioMed Central

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          Abstract

          Background

          The burden of post-malaria cognitive impairment is often overlooked. Given the large number of infections occurring worldwide, the magnitude of the problem is likely to be substantial. The objectives of this paper are; (i) to assess the evidence on post malarial cognitive impairment or impact on school education; (ii) to assess the possible positive impact of malaria drug prophylaxis on cognition; and (iii) to suggest recommendations on minimizing the burden of post-malarial cognitive impairment

          Methods

          PUBMED and SCOPUS were searched for all articles with the key word 'Malaria' in the title field and 'cognitive impairment' in any field. Google Scholar was searched for the same keywords anywhere in the article. The search was restricted to articles published in English within the last 15 years (1995-2010). After filtering of abstracts from the initial search, 44 papers had research evidence on this topic.

          Results & Discussion

          Cognitive abilities and school performance were shown to be impaired in sub-groups of patients (with either cerebral malaria or uncomplicated malaria) when compared with healthy controls. Studies comparing cognitive functions before and after treatment for acute malarial illness continued to show significantly impaired school performance and cognitive abilities even after recovery. Malaria prophylaxis was shown to improve cognitive function and school performance in clinical trials when compared to placebo groups. The implications of these findings are discussed.

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          Most cited references49

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          Cerebral malaria: mechanisms of brain injury and strategies for improved neurocognitive outcome.

          Cerebral malaria is the most severe neurological complication of infection with Plasmodium falciparum. With >575,000 cases annually, children in sub-Saharan Africa are the most affected. Surviving patients have an increased risk of neurological and cognitive deficits, behavioral difficulties, and epilepsy making cerebral malaria a leading cause of childhood neurodisability in the region. The pathogenesis of neurocognitive sequelae is poorly understood: coma develops through multiple mechanisms and there may be several mechanisms of brain injury. It is unclear how an intravascular parasite causes such brain injury. Understanding these mechanisms is important to develop appropriate neuroprotective interventions. This article examines possible mechanisms of brain injury in cerebral malaria, relating this to the pathogenesis of the disease, and explores prospects for improved neurocognitive outcome.
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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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              Malarial retinopathy: a newly established diagnostic sign in severe malaria.

              Severe malaria is commonly misdiagnosed in Africa, leading to a failure to treat other life-threatening illnesses. In malaria-endemic areas, parasitemia does not ensure a diagnosis of severe malaria because parasitemia can be incidental to other concurrent disease. The detection of malarial retinopathy is a candidate diagnostic test for cerebral malaria. Malarial retinopathy consists of a set of retinal abnormalities that is unique to severe malaria and common in children with cerebral malaria. Its presence and severity are related to risk of death and length of coma in survivors. A large, prospective autopsy study of children dying with cerebral malaria in Malawi found that malarial retinopathy was better than any other clinical or laboratory feature in distinguishing malarial from non-malarial coma. However, visualization has to date relied on specialist examination techniques. Further studies are planned to evaluate the usefulness of funduscopy by general clinicians in a variety of settings across Africa. Studies of the retina and retinal blood vessels provide an unparalleled opportunity to visualize an infected microvasculature and its effect on neural tissue in vivo. This report reviews current knowledge of malarial retinopathy, including its use as a diagnostic test in the comatose child, and its value as a tool for research into the pathophysiology of cerebral malaria.
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                Author and article information

                Journal
                Malar J
                Malaria Journal
                BioMed Central
                1475-2875
                2010
                20 December 2010
                : 9
                : 366
                Affiliations
                [1 ]Department of Parasitology, Faculty of Medicine, University of Colombo, 25, Kynsey Road, Colombo 8, Sri Lanka
                [2 ]University Medical Unit, National Hospital of Sri Lanka, Colombo, Sri Lanka
                [3 ]Department of Clinical Medicine, Faculty of Medicine, Colombo, Sri Lanka
                Article
                1475-2875-9-366
                10.1186/1475-2875-9-366
                3018393
                21171998
                bd3497bd-653e-4b1c-a0d1-f3c6b606186e
                Copyright ©2010 Fernando et al; licensee BioMed Central Ltd.

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

                History
                : 26 October 2010
                : 20 December 2010
                Categories
                Review

                Infectious disease & Microbiology
                Infectious disease & Microbiology

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