Emerging avenues for the management of cerebral malaria.

Abstract

Cerebral malaria (CM) is a lethal complication of Plasmodium falciparum infection. The multifactorial pathogenesis of the disease involving parasitic invasion of erythrocytes and sequestration of infected erythrocytes within the cerebral blood vessels leading to neuroinflammation and blood-brain barrier (BBB) disruption demands a multi-pronged treatment strategy. This article gives a brief overview of the pathogenesis of CM, challenges associated with its treatment and potential strategies to combat the same. There are several roadblocks in the successful treatment of CM. Resistance to artemisinin-based therapies has been reported in malaria-endemic regions. The paucity of targeted delivery to the brain necessitates the administration of antimalarials such as quinine in large doses causing toxic effects. There is a need for compounds to prevent oxidative stress, neuroinflammation and BBB disruption to decrease the menace of neurological sequelae associated with CM. Extensive research endeavours are now oriented towards investigating compounds that can act against neuroinflammation; developing brain-targeted nanocarriers to selectively deliver therapeutics against CM; and repurposing existing drugs and a combination of antimalarial and anti-inflammatory or immunomodulatory molecules for the treatment of CM. Protocols for evaluating novel proposed therapies against CM should be revisited to integrate monitoring of neurological parameters in parallel with the estimation of parasite load and survival.