Cerebral malaria

Overview

 * 5% of the world’s population is parasitized by malaria at any given time
 * 0.5-2.5 million deaths per year
 * Nearly all deaths (and neurologic complications) caused by Plasmodium falciparum
 * Cerebral Malaria – Case Definition
 * Deep level of unconsciousness with inability to localize a painful stimulus
 * P. falciparum asexual parasitemia
 * Hypoglycemia and other encephalopathies have been excluded
 * Coma should persist >6 hours in adults and >1 hour in children after a seizure

Pathophysiology & Etiology

 * Based on Age and Prior Exposure
 * < 2 years old – severe anemia
 * 2-18 years old – seizures/cerebral malaria
 * >18 years old – acute renal failure, pulmonary edema, liver dysfunction, cerebral malaria
 * All – metabolic acidosis (lactate)
 * Vector
 * Female Anopheles Mosquito
 * What’s in the Smear?
 * Ring forms mostly (occ banana gametocytes) – because trophozoites and schizonts are sequestered in vascular beds, causing pathology
 * Pathology
 * Sequestration of parasitized red blood cells (RBCs) in relatively hypoxic venous beds allows optimal parasite growth and prevents splenic destruction
 * Peripheral parasite count relatively poor predictor of sequestered biomass
 * Parasitized RBCs have electron dense “knobs” on surface, thought to be mediators of cytoadherence
 * Antigenic variation of “knobs” allow immune evasion
 * Decreased deformability of RBCs
 * Increased tumor necrosis factor (TNF) production

History and Symptoms

 * Diffuse encephalopathy
 * Febrile, unconscious, variable tone, usually lacking focal neurologic signs
 * No rash, no lymphadenopathy
 * Hypoglycemia common (8% adults, 20% children)
 * Seizures (10-50%)
 * Mortality 20% (8% ->50% if concomitant with renal failure and metabolic acidosis)
 * Most deaths occur within 48 hours of admission
 * Full recovery of consciousness takes a median of 2 days, but can take >1 week

Treatment

 * Supportive
 * IV Quinine (in US, Quinidine 10-20 mg/kg load followed by 0.02 mg/kg/min drip over 72 hours
 * Blood transfusion for hematocrit < 20
 * Correct hypoglycemia (but does not improve neurologic recovery)

Future or Investigational Therapies

 * Artemisin derivatives may replace quinine in the future
 * Exchange transfusion?