Neurological sequelae of pediatric Plasmodium falciparum cerebral malaria in Sub-Saharan Africa: A brief overview

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Kelly A. A. Leslie

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Abstract





Cerebral malaria, characterized by multiple seizures, coma, and other neurological abnormalities, is a particularly devastating complication of Plasmodium falciparum malaria. Children in sub-Saharan Africa comprise the most susceptible group to cerebral malaria worldwide, with more than 575,000 cases each year. Long-term neurological deficits – including motor impairments, language regression, cognitive deficits, behavioural abnormalities, and epilepsy – occur in approximately 25% of child survivors of cerebral malaria, which is now recognized as the leading cause of childhood neurodisability in sub- Saharan Africa. These neurological sequelae generate an enormous economic and social burden as child survivors’ impaired intellectual function and learning abilities have a substantial impact on their prospects for education and future employment. The aim of this article is to provide a brief overview of the current literature on the neurological sequelae of pediatric cerebral malaria, as well as offer suggestions for future research. While the current understanding of risk factors, disease mechanisms, and treatments for these neurological deficits is lacking, recent studies have shown great promise in revolutionizing the way that cerebral malaria is diagnosed and treated. It is speculated that an inflammatory response to malarial antigens in neural blood vessels triggers a cascade of events that ultimately results in cerebral tissue damage, high intracranial pressure, and hemorrhaging into the brain, resulting in long-term brain damage. Potential risk factors for neurological deficits include the duration of coma, the occurrence of multiple seizures, and high fever. Malaria retinopathy, angiopoietin-1 and -2, and EEG patterns are being investigated as potential biomarkers to improve the definitive diagnosis of cerebral malaria. New drug therapies that endeavor to prevent long-term neurological deficits after cerebral malaria include erythropoietin and statins, as well as cognitive rehabilitation and physical and speech therapy, the latter having been shown to be successful among survivors.