A comprehensive review of cerebral malaria

Plasmodium falciparum malaria presents a substantial threat as an infectious disease causing the most severe neurological complication- Cerebral malaria (CM). CM is responsible for approximately 400,000 annual fatalities among African children, constituting over 90% of the total deaths attributed to malaria. Remarkably, the mortality rate for children succumbing to severe malaria complicated by CM has remained relatively stable over the past decade, ranging between 0.15 and 0.25. The pathogenesis of CM is poorly understood, innumerable theories have explained the pathophysiological mechanisms but hitherto there are no firm conclusions about it. Insufficient access to human samples poses a significant obstacle to advancing research in Cerebral Malaria (CM). However, various post-mortem histopathological studies of human tissues and mice models of CM have revealed the parasite's adherence within the cerebral microvasculature. This adherence is thought to be crucial in the development of the condition, contributing to subsequent pathological alterations in the surrounding tissue and ultimately leading to neural dysfunction. It also leads to the breakdown of the Blood-Brain Barrier leading to haemorrhages. This clinical syndrome is primarily characterized by a significant impairment in consciousness or a state of coma. Patients who survive often experience prolonged neurological complications, such as hemiplegia, partial paralysis, seizure disorders, ataxia, changes in behaviour, and cognitive deficits. To date, several adjunctive treatment approaches have yielded limited success, and numerous attempts to develop effective neuroprotective adjunctive therapies have failed, emphasizing the pressing need for advancements in this area.