1:00 pm, Monday, 19 June
Room BIG13, Ground Floor
Biochemistry Building
710 Cumberland St
Prof Bruce Russell
Microbiology & Immunology
Unravelling the Pathogenesis of Cerebral Malaria: Insights from Plasmodium coatneyi-Infected Rhesus Macaques and the Promising Therapeutic Role of Methylene Blue
Cerebral malaria (CM) is an often-fatal neurological complication of Plasmodium falciparum infection, and survivors often experience enduring neurologic sequelae. The pathogenesis of human CM is complex and the exact underlying factors to severe neurological complications are not well understood, although a few studies have shown blood-brain barrier (BBB) disruption as one of the key factors leading to CM progression. To unravel the etiology of human CM for diagnostic and therapeutic purposes, Plasmodium coatneyi-infected rhesus macaques were used in this study as a non-human primate (NHP) model for severe malaria, as they share similar pathophysiological features with P. falciparum infection in humans. Differential gene expression analysis revealed the effectiveness of methylene blue treatment as it reversed the effects of infection on the brainstem. By comparing our brainstem dataset of P. coatneyi-infected Macaca mulatta with two other transcriptomic datasets (P. coatneyi-infected M. mulatta blood and P. falciparum-infected human blood), we have successfully identified 9 genes associated with CM severity. Many of these genes could potentially serve as blood biomarkers for the future diagnosis of falciparum lethal CM.
