What is the treatment for cerebral malaria?

Treatment of Cerebral Malaria

Intravenous artesunate is the definitive first-line treatment for cerebral malaria, administered at 2.4 mg/kg IV at 0,12,24, and 48 hours, providing superior outcomes and faster parasite clearance compared to quinine. 1, 2

Immediate Antimalarial Treatment

First-Line: Intravenous Artesunate

• Administer IV artesunate at 2.4 mg/kg at 0,12,24, and 48 hours as recommended by the World Health Organization 1, 2
• Continue for at least 3 doses until clinical improvement occurs and parasitemia drops below 1% 2
• Once the patient can tolerate oral medications and parasitemia is <1%, switch to a complete oral artemisinin-based combination therapy course 1
• Artesunate provides faster parasite clearance (90% clearance in 16-18 hours vs 34.5 hours with quinine) and reduced mortality compared to quinine 3, 4

Second-Line: Intravenous Quinine (if artesunate unavailable)

• Loading dose: 20 mg salt/kg IV over 4 hours (or 3 hours per older protocols), followed by 10 mg/kg every 8-12 hours 5, 1
• Omit the loading dose if the patient received quinine or mefloquine in the previous 24 hours 1, 6
• Switch to oral therapy after completing at least 48 hours of IV treatment when feasible 1
• Monitor for QT prolongation and hypoglycemia due to insulin release 1

Critical Supportive Care Measures

Hypoglycemia Management

• Monitor blood glucose regularly as hypoglycemia is a common complication and independent risk factor for death 5, 1, 6
• Suspect hypoglycemia with any clinical deterioration, especially new neurologic findings 5
• Treat with 50 mL of 50% IV dextrose if hypoglycemia is detected or suspected 1, 6

Fluid Management

• Use restrictive fluid therapy to avoid pulmonary or cerebral edema 1, 2, 6
• Fluid overload can precipitate ARDS and worsen cerebral edema 5, 1
• Preferred IV fluid: 5% dextrose with 1/2 normal saline to prevent hypoglycemia while minimizing salt leakage into pulmonary and cerebral tissues 5, 6
• In volume depletion, administer fluid to maintain cardiac output and renal perfusion, but exercise extreme caution 5

Seizure Management

• For active seizures: lorazepam 0.1 mg/kg IV/IO as first-line 1
• If seizure persists, repeat lorazepam 0.1 mg/kg 1
• Alternative: paraldehyde 0.2 mL/kg IM, repeat if convulsions recur 1, 6
• For refractory seizures: phenobarbital 10 mg/kg IM 1, 6
• Do NOT use prophylactic anticonvulsants as prophylactic phenobarbital increased mortality in children with cerebral malaria, particularly when combined with multiple doses of diazepam due to respiratory depression 1

Raised Intracranial Pressure

• Treat as a medical emergency with rapid intubation and mechanical ventilation 1
• Maintain PaCO2 in the normal range 1
• Consider mannitol 0.5 mg/kg IV over 5-10 minutes 1
• Never administer steroids as they have an adverse effect on outcomes in cerebral malaria 5, 1, 6

Blood Transfusion Indications

• Hemoglobin <4 g/dL 5, 1, 6
• Hemoglobin <6 g/dL with signs of heart failure (dyspnea, enlarging liver, gallop rhythm) 5, 1, 6
• Perform blood grouping and cross-matching when hemoglobin is below 4 g/dL 5, 2

Essential Diagnostic Tests

• Perform immediately upon admission: thick blood film, hemoglobin, blood glucose, and lumbar puncture 5, 2, 6
• Lumbar puncture is essential to rule out other causes of meningitis/encephalitis, as cerebral malaria can present with CSF pleocytosis 1, 6

Monitoring Requirements

Parasitemia Monitoring

• Monitor every 12 hours until decline to <1%, then every 24 hours until negative 1, 2, 6
• Note that parasitemia may increase in the first 24 hours with quinine, which is not indicative of treatment failure 1

Post-Treatment Surveillance

• Monitor for post-artesunate delayed hemolysis (PADH) at days 7,14,21, and 28 1, 2, 6
• Check hemoglobin, haptoglobin, and lactate dehydrogenase 1

Antibiotic Considerations

• Start antibiotics only if bacterial co-infection is suspected 1, 2, 6
• Continue antibiotics only if blood cultures are positive 1, 2, 6

Important Caveats

• Exchange transfusion is NOT indicated with artesunate availability 1, 2, 6
• Anemia from malaria will reverse spontaneously after antimalarial therapy, though it may progress for several weeks after successful treatment 5
• Iron replacement is helpful only if coexisting iron deficiency exists; folic acid may be helpful during recovery 5
• Despite optimal treatment, cerebral malaria can result in long-term neurological sequelae 6
• The mortality rate with artesunate treatment is approximately 6.9-8.3%, significantly lower than the 34.3% mortality with quinine 7, 4