Abstract
SummaryBackgroundCerebral malaria, a disorder characterised by coma, parasitaemia, and no other evident cause of coma, is challenging to diagnose definitively in endemic regions that have high rates of asymptomatic parasitaemia and limited neurodiagnostic facilities. A recently described malaria retinopathy improves diagnostic specificity. We aimed to establish whether retinopathy-positive cerebral malaria is a risk factor for epilepsy or other neurodisabilities.MethodsBetween 2005 and 2007, we did a prospective cohort study of survivors of cerebral malaria with malaria retinopathy in Blantyre, Malawi. Children with cerebral malaria were identified at the time of their index admission and age-matched to concurrently admitted children without coma or nervous system infection. Initially matching of cases to controls was 1:1 but, in 2006, enrolment criteria for cerebral malaria survivors were revised to limit inclusion to children with cerebral malaria and retinopathy on the basis of indirect ophthalmoscopic examination; matching was then changed to 1:2 and the revised inclusion criteria were applied retrospectively for children enrolled previously. Clinical assessments at discharge and standardised nurse-led follow-up every 3 months thereafter were done to identify children with new seizure disorders or other neurodisabilities. A Kaplan-Meier survival analysis was done for incident epilepsy.Findings132 children with retinopathy-positive cerebral malaria and 264 age-matched, non-comatose controls were followed up for a median of 495 days (IQR 195–819). 12 of 132 cerebral malaria survivors developed epilepsy versus none of 264 controls (odds ratio [OR] undefined; p<0·0001). 28 of 121 cerebral malaria survivors developed new neurodisabilities, characterised by gross motor, sensory, or language deficits, compared with two of 253 controls (OR 37·8, 95% CI 8·8–161·8; p<0·0001). The risk factors for epilepsy in children with cerebral malaria were a higher maximum temperature (39·4°C [SD 1·2] vs 38·5°C [1·1]; p=0·01) and acute seizures (11/12 vs 76/120; OR 6·37, 95% CI 1·02–141·2), and male sex was a risk factor for new neurodisabilities (20/28 vs 38/93; OR 3·62, 1·44–9·06).InterpretationAlmost a third of retinopathy-positive cerebral malaria survivors developed epilepsy or other neurobehavioural sequelae. Neuroprotective clinical trials aimed at managing hyperpyrexia and optimising seizure control are warranted.FundingUS National Institutes of Health and Wellcome Trust.
Highlights
A disorder characterised by coma, parasitaemia, and no other evident cause of coma,[1] affects about half a million children every year, primarily in sub-Saharan Africa.[2]
Participants We did a prospective cohort study of cerebral malaria survivors who were admitted to the paediatric research ward of Queen Elizabeth Central Hospital (QECH), Blantyre, Malawi, during the malaria season (January– June) from 2005 to 2007 and who resided within the catchment area
Because QECH is in a region endemic for malaria, which is one of the commonest causes of illness in Malawian children, all comatose children admitted to QECH have a thick blood film reviewed to screen for Plasmodium falciparum
Summary
A disorder characterised by coma, parasitaemia, and no other evident cause of coma,[1] affects about half a million children every year, primarily in sub-Saharan Africa.[2] The case-fatality rate of cerebral malaria is estimated to be about 15%, with risk factors for death being deeper coma or coma of longer duration, younger age, seizures, hypoglycaemia, and hyperparasitaemia.[3,4] Neurological sequelae, including cortical blindness, gross motor deficits, ataxia, language regression, epilepsy, and behavioural abnormalities, have been reported at discharge in 10–20% of survivors, with follow-up assessments suggesting that gross deficits usually resolve within a few weeks of recovery.[4,5,6,7,8,9]. Previous outcome studies, which are reviewed systematically in the webappendix, have relied upon the standard clinical case definition of cerebral malaria
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