Plasmodium knowlesi is an emerging zoonotic malaria species and a leading cause of malaria in
Malaysia. Although severe disease is increasingly recognised, cerebral malaria remains uncommon
and is traditionally associated with Plasmodium falciparum. We report a fatal case of cerebral malaria
caused by P. knowlesi in a previously healthy 61-year-old woman with a history of frequent orchard
visits for peridomestic agricultural activities. She presented with rapid neurological deterioration and
circulatory shock, complicated by an acute pontine infarction. Peripheral blood smear and polymerase
chain reaction confirmed P. knowlesi infection with a parasite density of approximately 35,000 parasites/
µL. The patient met World Health Organization criteria for severe malaria and was treated promptly
with intravenous artesunate in accordance with international guidelines, alongside intensive supportive
care for septic shock and multiorgan failure. Despite a rapid reduction in parasitaemia, her condition
deteriorated, and she died within 24 hours of presentation. This case highlights the potential for
P. knowlesi to cause rapidly progressive and fatal cerebral malaria. Clinicians in endemic regions should
maintain a high index of suspicion for zoonotic malaria in patients presenting with acute neurological
deterioration.