Cerebral malaria

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

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)

Contraindicated Medications

• Prednisolone

Future or Investigational Therapies

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