What is the recommended treatment for severe Plasmodium (malaria) falciparum infection?

Treatment of Severe Plasmodium Falciparum Malaria

Intravenous artesunate is the first-line treatment for severe falciparum malaria, administered at 2.4 mg/kg at 0,12, and 24 hours, then daily until parasitemia is <1% and the patient can tolerate oral medication. 1

Initial Management

• Diagnosis and Assessment:

  • Identify criteria for severe malaria: impaired consciousness, seizures, respiratory distress, shock, jaundice, severe anemia (Hb <7g/dL), acidosis, hypoglycemia (<40 mg/dL), hyperparasitemia (>5% in non-immune, >10% in semi-immune), or renal failure (creatinine >3 mg/dL) 2
  • Parasitemia >4% is the most frequent criterion for severe malaria requiring ICU admission in Europe 2

• Immediate Treatment:

  • Administer IV artesunate 2.4 mg/kg at 0,12, and 24 hours 1
  • Continue daily dosing until parasitemia is <1% and patient can take oral medication 2, 1
  • The large inter-individual variability in drug levels suggests 2.4 mg/kg should be considered the minimum dose 3

Follow-up Treatment

• Once clinical improvement occurs and parasitemia is <1%, transition to a complete oral course of artemisinin-based combination therapy (ACT) 2, 1
• Options include:
  • Dihydroartemisinin-piperaquine (preferred)
  • Artemether-lumefantrine (preferred)
  • Atovaquone-proguanil (alternative)
  • Mefloquine (alternative, if contraindications to other options) 2

Supportive Care

• Fluid Management:

  • Use restrictive fluid management to avoid pulmonary or cerebral edema 2, 1
  • This approach does not worsen kidney function or tissue perfusion 2

• Renal Protection:

  • Consider acetaminophen (1g every 6 hours for 72 hours) for potential renoprotective effects in acute kidney injury 2, 1

• Hypoglycemia Management:

  • Monitor glucose levels regularly
  • Correct hypoglycemia with 5 mL/kg of 10% dextrose 1

• Antibiotic Therapy:

  • Start antibiotics only if bacterial co-infection is suspected
  • Discontinue if blood cultures are negative 2, 1

Monitoring

• Check parasitemia every 12 hours until <1%, then every 24 hours until negative 2, 1
• Monitor complete blood count, renal function, liver function, and blood gases daily 1
• Watch for post-artesunate delayed hemolysis (PADH) at days 7,14,21, and 28 after treatment 2, 1

Important Considerations

• Exchange blood transfusion is no longer recommended with the availability of artesunate 2, 1
• Delayed treatment significantly increases mortality - treat as a medical emergency 1
• Asplenic patients are at higher risk for severe malaria and complications 1
• In cases of reduced ring stage sensitivity to artemisinin, parasite clearance may be slower with standard dosing regimens 4

Potential Complications

• Post-artesunate delayed hemolysis can occur and requires monitoring 2, 1
• Haemolytic anemia has been reported with artemisinin derivatives, including oral forms 5
• Artesunate has shown a 34.7% reduction in mortality compared to quinine (15% vs 22%), with greatest benefit in patients with high parasite counts 6

Severe falciparum malaria is a medical emergency requiring prompt treatment with intravenous artesunate, followed by appropriate oral therapy once the patient improves, along with careful monitoring and supportive care to reduce mortality and prevent complications.