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      Cerebral malaria is associated with long-term mental health disorders: a cross sectional survey of a long-term cohort

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          Abstract

          Background

          Cerebral malaria (CM) and severe malarial anaemia (SMA) are associated with neuro-developmental impairment in African children, but long-term mental health disorders in these children are not well defined.

          Methods

          A cohort of children previously exposed to CM (n = 173) or SMA (n = 99) had neurologic assessments performed and screening for behaviour difficulties using the Strengths and Difficulties Questionnaire (SDQ) a median of 21 months after the disease episode. These findings were compared to concurrently recruited community children (CC, n = 108). Participants with SDQ total difficulties score ≥17 had a mental health interview with the child and adolescent version of the Mini-International Neuropsychiatric Interview (MINI-KID) and a sample had brain magnetic resonance imaging (MRI).

          Results

          Fifty-five children had SDQ score ≥17. On the MINI-KID, these children were classified as having no difficulties (n = 18), behaviour difficulties only (n = 13) or a mental health disorder (n = 24). Behaviour difficulties were seen in similar frequencies in CM (3.5 %), SMA (4.0 %) and CC (2.8 %). In contrast, mental health disorders were most frequent in CM (10.4 %), followed by SMA (4.0 %) and CC (1.8 %). Externalizing disorders (conduct, oppositional defiance and attention deficit hyperactivity) were the most common mental health disorders. The median total coma duration was 72 (IQR 36.0–115.0) h in patients with mental health disorders compared to 48 (IQR 28.5–78.7) h in those without, p = 0.039. Independent risk factors for mental health disorder included neurologic deficit at discharge (OR 4.09 (95 % CI 1.60, 10.5) and seizure recurrences during hospitalization, (OR 2.80, 95 % CI 1.13, 6.97). Brain MRI findings consistent with small vessel ischaemic neural injury was seen in over half of these children.

          Conclusions

          Cerebral malaria may predispose children to mental health disorders, possibly as a consequence of ischaemic neural injury. There is urgent need for programmes of follow-up, diagnosis and interventions for these children.

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          Most cited references10

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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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            Severe malarial anemia is associated with long-term neurocognitive impairment.

            Cerebral malaria (CM) is associated with long-term neurocognitive impairment in children ≥5 years of age. No prospective studies to date have assessed neurocognitive impairment in children with CM <5 years of age, or in children with severe malarial anemia (SMA), a form of severe malaria estimated to affect as many as 5 million children annually.
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              Severe neurological sequelae and behaviour problems after cerebral malaria in Ugandan children

              Background Cerebral malaria is the most severe neurological complication of falciparum malaria and a leading cause of death and neuro-disability in sub-Saharan Africa. This study aimed to describe functional deficits and behaviour problems in children who survived cerebral malaria with severe neurological sequelae and identify patterns of brain injury. Findings Records of children attending a specialist child neurology clinic in Uganda with severe neurological sequelae following cerebral malaria between January 2007 and December 2008 were examined to describe deficits in gross motor function, speech, vision and hearing, behaviour problems or epilepsy. Deficits were classified according to the time of development and whether their distribution suggested a focal or generalized injury. Any resolution during the observation period was also documented. Thirty children with probable exposure to cerebral malaria attended the clinic. Referral information was inadequate to exclude other diagnoses in 7 children and these were excluded. In the remaining 23 patients, the commonest severe deficits were spastic motor weakness (14), loss of speech (14), hearing deficit (9), behaviour problems (11), epilepsy (12), blindness (12) and severe cognitive impairment (9). Behaviour problems included hyperactivity, impulsiveness and inattentiveness as in attention deficit hyperactivity disorder (ADHD) and conduct disorders with aggressive, self injurious or destructive behaviour. Two patterns were observed; a) immediate onset deficits present on discharge and b) late onset deficits. Some deficits e.g. blindness, resolved within 6 months while others e.g. speech, showed little improvement over the 6-months follow-up. Conclusions In addition to previously described neurological and cognitive sequelae, severe behaviour problems may follow cerebral malaria in children. The observed differences in patterns of sequelae may be due to different pathogenic mechanisms, brain regions affected or extent of injury. Cerebral malaria may be used as a new model to study the pathogenesis of ADHD.
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                Author and article information

                Contributors
                +256 414 531875 , ridro1@gmail.com
                angelina_kakooza@yahoo.co.uk
                jbasea@googlemail.com
                kssebyala@gmail.com
                pbangirana@yahoo.com
                opokabob@yahoo.com
                klubowa@yahoo.com
                semru002@umn.edu
                chjohn@iu.edu
                joycenalugya@yahoo.com
                Journal
                Malar J
                Malar. J
                Malaria Journal
                BioMed Central (London )
                1475-2875
                31 March 2016
                31 March 2016
                2016
                : 15
                : 184
                Affiliations
                [ ]Department of Paediatrics and Child Health, Mulago Hospital, Makerere University College of Health Sciences, P.O Box 7072, Kampala, Uganda
                [ ]Neuropediatric Research Unit, Astrid Lindgren Children’s Hospital, Karolinska Institutet, Solna, Stockholm Sweden
                [ ]Department of Pediatrics, University of Minnesota, Minneapolis, DE USA
                [ ]Departments of Pediatrics, Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, USA
                Article
                1233
                10.1186/s12936-016-1233-6
                4815157
                27030124
                09b5c963-0f28-43bd-be13-d915d31ef197
                © Idro et al. 2016

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 2 October 2015
                : 15 March 2016
                Funding
                Funded by: National Institute of Neurological Disorders and Stroke and the Fogarty International Center
                Award ID: R01NS055349
                Award Recipient :
                Funded by: Waterloo Foundation
                Award ID: 1025/1398
                Award Recipient :
                Categories
                Research
                Custom metadata
                © The Author(s) 2016

                Infectious disease & Microbiology
                behaviour,mental health,psychiatric,disorder,children,cerebral malaria

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