What is the recommended treatment for cerebral malaria with cerebrospinal fluid (CSF) pleocytosis?

Treatment of Cerebral Malaria with CSF Pleocytosis

Intravenous artesunate is the first-line treatment for cerebral malaria with CSF pleocytosis, with faster parasite clearance and better outcomes compared to quinine. 1, 2

Initial Management

• Immediate hospitalization is essential with prompt diagnostic workup including thick blood film, hemoglobin measurement, blood glucose, and lumbar puncture 3, 2
• Administer intravenous artesunate at 2.4 mg/kg at 0,12,24, and 48 hours, continuing for at least 3 doses until clinical improvement and parasitemia is <1% 1, 2
• If artesunate is unavailable, use intravenous quinine: initial dose of 20 mg(salt)/kg body weight in 10 mL/kg 5% dextrose infused over 3 hours, followed by 10 mg/kg every 12 hours 3, 2
• For patients who have already received quinine before admission, reduce the initial dose to 10 mg/kg 3
• Despite the presence of CSF pleocytosis, continue antimalarial treatment as the primary intervention 2

Management of CSF Pleocytosis

• CSF pleocytosis may be present in cerebral malaria, but this should not alter the primary antimalarial treatment approach 2
• Continue treatment for malaria while considering concomitant bacterial meningitis 3
• If bacterial meningitis is suspected, start appropriate antibiotics while continuing antimalarial treatment 2
• Lumbar puncture is essential to rule out other causes of meningitis or encephalitis 2

Supportive Care and Management of Complications

• Carefully manage fluid therapy to prevent fluid overload, which can precipitate pulmonary edema or ARDS and worsen cerebral edema 3, 2
• Use 5% dextrose with 1/2 normal saline as the IV fluid of choice to prevent hypoglycemia and minimize salt leakage into pulmonary and cerebral tissues 3, 2
• Monitor blood glucose levels regularly and treat hypoglycemia with 50 mL of 50% IV dextrose if detected or suspected 3, 1
• For seizures, administer appropriate anticonvulsants following the Advanced Pediatric Life Support Group algorithm 3
• Blood transfusion is indicated when hemoglobin is below 4 g/dL, or below 6 g/dL with signs of heart failure 3, 2
• Do NOT administer steroids, as they have an adverse effect on outcomes in cerebral malaria 3, 1
• Exchange blood transfusion is no longer indicated with the availability of artesunate 1, 2

Monitoring and Follow-up

• Monitor parasitemia every 12 hours until decline to <1%, then every 24 hours until negative 3, 2
• For patients treated with IV artesunate, monitor for post-artemisinin delayed hemolysis (PADH) at days 7,14,21, and 28 3, 1
• Start antibiotics if concomitant bacterial infection is suspected, but continue only if blood cultures are positive 3, 2
• Monitor for renal failure by tracking fluid intake and output 3, 2
• In case of oliguria, a fluid challenge followed by furosemide injection can help differentiate acute renal failure from prerenal causes 3

Special Considerations

• Dihydroartemisinin (the active metabolite of artesunate) penetrates the CSF, making it effective for cerebral malaria 4
• Switch to oral medications as soon as the patient's condition allows 3, 2
• Despite advances in treatment, cerebral malaria can still result in long-term neurological sequelae even with appropriate treatment 2, 5
• Recent research suggests that interactions between infected red blood cells and endothelial protein C receptor (EPCR) play a critical role in cerebral malaria pathophysiology 5