Cerebral malaria (CM) is the most severe neurological complication resulting from infection with the Plasmodium falciparum parasite. Defined by coma in the presence of laboratory-confirmed P. falciparum infection, CM is a medical emergency demanding immediate hospitalization, often in an intensive care setting. Untreated, CM is nearly always fatal; even with optimal treatment, mortality rates remain significant, often ranging between 15 and 20%. Rapid intervention is necessary because severe systemic effects and neurological injury progress quickly, making timely treatment crucial for patient survival and long-term outcome.
Immediate Medical Stabilization
Initial management focuses on immediate life support and correcting metabolic disturbances. Healthcare providers must rapidly assess and secure the patient’s airway, manage breathing through supplemental oxygen or mechanical ventilation if necessary, and support circulation. Hypoglycemia, a common and dangerous complication, requires immediate correction, typically with a bolus of 50% intravenous dextrose in adults or 10% dextrose in children, followed by a continuous glucose infusion to maintain normal blood sugar levels.
Managing circulatory shock requires careful fluid administration, which is challenging due to the high risk of exacerbating cerebral edema. A conservative fluid strategy is recommended, with maintenance fluids typically administered at 1 to 2 milliliters per kilogram per hour in patients without shock. Aggressive fluid boluses are avoided unless the patient exhibits clear signs of hypotensive shock, as excessive fluid can rapidly increase intracranial pressure and worsen neurological outcome. The goal is to maintain adequate tissue perfusion while preventing fluid overload.
Targeted Antimalarial Therapy
The definitive treatment for cerebral malaria involves the immediate administration of parenteral antimalarial medication. Intravenous artesunate is the current standard of care and the preferred first-line drug over older treatments like quinine. Clinical trials established artesunate’s superiority, demonstrating lower mortality rates and a significantly faster parasite clearance time. This rapid action is crucial for severe illness, as it quickly reduces the number of infected red blood cells that block cerebral blood flow.
Artesunate is an artemisinin derivative metabolized into the active compound dihydroartemisinin (DHA). Once inside the parasite-infected red blood cell, DHA is activated by iron, generating toxic free radicals that damage parasite proteins and membranes. Artesunate is administered intravenously in a weight-based dose at admission, then again at 12 and 24 hours, followed by once-daily dosing until the patient can transition to oral medication.
The transition from intravenous to oral therapy is monitored to ensure complete parasite eradication and prevent recurrence. Patients are switched once they are clinically stable, able to tolerate oral intake, and the parasite density has dropped to \(\le 1\%\). The parenteral treatment is followed by a full three-day course of an Artemisinin-based Combination Therapy (ACT), such as artemether-lumefantrine or dihydroartemisinin-piperaquine. ACT combines the fast-acting artesunate derivative with a longer-acting partner drug to eliminate any remaining parasites.
Managing Severe Complications
Beyond antimalarial therapy, treatment involves managing complications arising from the disease. Seizures are common, especially in children, and require prompt intervention but not prophylactic treatment. Active, prolonged seizures are treated immediately with first-line benzodiazepines, such as lorazepam or diazepam, to stop convulsive activity and prevent secondary brain injury.
Cerebral edema is a characteristic feature of CM, particularly in children, and may lead to dangerously raised intracranial pressure. Management focuses on non-pharmacological measures, including positioning the patient with the head elevated to optimize venous drainage and avoiding unnecessary fluid administration. Osmotic agents like mannitol are used with caution; studies show they may prolong coma and potentially increase mortality in some cases.
Acute kidney injury (AKI) is a frequent complication, managed through conservative fluid balance and close monitoring of urine output. If AKI progresses, renal replacement therapy, such as dialysis, may be necessary. Severe anemia is corrected with blood transfusions. Transfusion is typically indicated when the hemoglobin level drops below 40 g/L, or below 60 g/L if the patient exhibits signs of severe systemic distress like acidosis or impaired consciousness.
Prognosis and Recovery
The immediate prognosis is linked to the depth and duration of the coma, the presence of metabolic acidosis, and the severity of multi-organ complications. Most patients who survive the acute phase, particularly adults, experience a complete neurological recovery. However, a significant proportion of survivors, especially children, may be left with long-term neurological sequelae.
The prevalence of neurological deficits at discharge can be as high as 12 to 29% in children, though many symptoms are transient. Common long-term effects include cognitive impairment (affecting learning and behavior) and focal deficits such as hemiplegia, ataxia, or epilepsy. Long-term monitoring and neuro-rehabilitation are important components of post-recovery care to mitigate these effects and support the child’s development.