Cerebral malaria

# Overview
- 5% of the worlds 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
- 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
- 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)
- < 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
- Female Anopheles Mosquito
- Whats in the Smear?
Ring forms mostly (occ banana gametocytes)  because trophozoites and schizonts are sequestered in vascular beds, causing pathology
- 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
- 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
- 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?