Cerebral Malaria

Cerebral malaria is severe falciparum malaria with unarousable coma (Blantyre coma score 2 or less, Glasgow Coma Scale 10 or less) persisting at least 1 hour after a seizure, with exclusion of other causes of encephalopathy. It occurs mostly in African children under 5 years and non immune adults.

• Mechanism: sequestration of infected red cells in cerebral microvasculature, endothelial activation, raised intracranial pressure in children.
• Mortality 15 to 25 percent despite treatment; neurological sequelae in 10 to 25 percent of survivors.

Fever followed by seizures, drowsiness progressing to coma, abnormal posturing (decorticate, decerebrate), conjugate gaze or roving eye movements, hypoglycaemia, and respiratory irregularity.

• Retinopathy (retinal whitening, vessel changes, haemorrhages, papilloedema) in children is specific.
• Differential diagnosis: bacterial meningitis, viral encephalitis, tuberculous and cryptococcal meningitis, hypoglycaemia, post ictal state, sepsis, diabetic ketoacidosis, uraemia, hepatic encephalopathy, poisoning, subdural haematoma, stroke, febrile seizures.
• Complications: persistent seizures, status epilepticus, brain herniation, hypoglycaemia, aspiration pneumonia, acute kidney injury, long term neurological deficits (hemiparesis, ataxia, cortical blindness, cognitive and speech disorders, epilepsy, behavioural change).

Positive malaria test with coma exclusion of other causes.

• Rapid test and blood film with parasite count; blood glucose at admission and every 4 hours; haemoglobin, electrolytes, creatinine, lactate, bicarbonate, blood culture.
• Lumbar puncture when safe (no signs of raised intracranial pressure) to exclude meningitis; start antibiotics first if delayed.
• CT head in adults or focal signs; fundoscopy; EEG if seizures persist.

Immediate IV artesunate and stabilisation of airway, glucose and seizures.

• Supportive: airway protection and oxygen, left lateral position, head up 30 degrees, nasogastric tube for feeding and glucose, strict fluid balance (avoid overload and hypovolaemia), nurse in intensive or high dependency care, frequent coma scoring, bladder catheter, pressure care.
• Pharmacological: artesunate 2.4 mg/kg IV (children under 20 kg 3 mg/kg) at 0, 12 and 24 hours then daily, to a minimum of 24 hours, then a complete oral artemisinin combination (artemether lumefantrine or dihydroartemisinin piperaquine). Hypoglycaemia: 10 percent dextrose 5 mL/kg IV then maintenance infusion with 10 percent dextrose; check glucose every 4 hours. Seizures: diazepam 0.3 mg/kg rectal or 0.1 to 0.2 mg/kg IV (adults 10 mg IV), repeat once after 10 minutes; then phenobarbital 15 mg/kg IV or phenytoin 15 to 20 mg/kg IV over 30 minutes. Empirical ceftriaxone 100 mg/kg/day in children or 2 g IV twice daily in adults until meningitis is excluded. Paracetamol 15 mg/kg every 6 hours. Avoid corticosteroids, mannitol and other agents for intracranial pressure unless evidence of herniation. Transfuse for haemoglobin under 5 g/dL (or under 7 g/dL with respiratory distress).
• Procedures: lumbar puncture (if safe), intubation and ventilation for Glasgow Coma Scale 8 or less, repeated seizures or respiratory failure, haemodialysis for renal failure.
• Special groups: pregnancy, IV artesunate in all trimesters, treat hypoglycaemia aggressively, obstetric input; children, neurological and sensory follow-up at 6 months; HIV, continue antiretroviral therapy where possible.
• Red flags: Glasgow Coma Scale falling, pupillary changes, bradycardia with hypertension, persistent seizures, hypoglycaemia, respiratory failure, lactate over 5 mmol/L, parasite density not falling.
• Follow-up: coma recovery generally within 24 to 72 hours; developmental and neurocognitive review at discharge and 3 to 6 months; physiotherapy and school support for sequelae.