Is dual intravenous (IV) artesunate and intravenous (IV) chloroquine recommended for the treatment of Plasmodium falciparum malaria?

Treatment of Severe Plasmodium falciparum Malaria: IV Artesunate Alone is Recommended, Not Dual Therapy

Intravenous (IV) artesunate alone is the first-line treatment for severe Plasmodium falciparum malaria, and dual therapy with IV chloroquine is not recommended. 1, 2

First-Line Treatment for Severe P. falciparum Malaria

IV Artesunate Regimen

• Dosing: 2.4 mg/kg IV at 0,12, and 24 hours, then daily until parasitemia is <1% and patient can take oral medication 1, 2
• Efficacy: Superior to quinine with:
  • Faster parasite clearance
  • Shorter ICU stays
  • Lower mortality (15% vs 22%, absolute reduction of 34.7%) 2, 3
• Monitoring: Check parasitemia every 12 hours until <1%, then every 24 hours until negative 2

Why Not Dual Therapy with Chloroquine

1. No evidence supports combining IV artesunate with IV chloroquine for P. falciparum
2. Current guidelines recommend artesunate monotherapy for the parenteral phase 1, 2
3. Adding chloroquine could potentially:
   • Increase risk of adverse effects
   • Complicate monitoring
   • Provide no additional benefit over artesunate alone

Treatment Algorithm for Severe P. falciparum Malaria

1. Initial Assessment:

   • Confirm diagnosis of severe P. falciparum malaria
   • Identify severity criteria (parasitemia >1%, impaired consciousness, respiratory distress, etc.)

2. First-Line Treatment:

   • Administer IV artesunate 2.4 mg/kg at 0,12, and 24 hours, then daily 1, 2
   • Continue until parasitemia <1% and patient can take oral medication

3. If IV Artesunate Unavailable:

   • Use IV quinine as second-line (20 mg salt/kg loading dose over 4 hours, followed by 10 mg/kg over 4 hours every 8 hours) 1
   • Monitor for adverse effects (QT prolongation, hypoglycemia)

4. Transition to Oral Therapy:

   • Once parasitemia <1% and patient can take oral medication
   • Complete full course with one of:
     • Dihydroartemisinin-piperaquine
     • Artemether-lumefantrine
     • Atovaquone-proguanil
     • Mefloquine 1, 2

Supportive Care

• Restrictive fluid management to avoid pulmonary or cerebral edema 2
• Consider acetaminophen (1g every 6 hours) for potential renoprotective effects 2
• Monitor and correct hypoglycemia with 10% dextrose if needed 2
• Monitor electrolytes, especially potassium 2
• Start antibiotics only if bacterial co-infection is suspected 2

Important Considerations

Pharmacokinetic Variability

• Large inter-individual variability (10-fold) in dihydroartemisinin (active metabolite) concentrations after IV artesunate administration 4
• This variability supports using the recommended 2.4 mg/kg dose as the minimum 4

Monitoring Response

• Parasitemia should decrease markedly within 3 days of therapy 2
• If parasitemia not decreasing appropriately, consider alternative therapy 2
• Post-artesunate delayed hemolysis (PADH) is a potential adverse effect requiring monitoring 1

Special Populations

• Pregnant women can receive IV artesunate with careful monitoring 2
• Children can be treated with the same medications using weight-adjusted dosing 2
• Asplenic patients may have higher parasitemia levels and require more intensive monitoring 2

Conclusion

For severe P. falciparum malaria, IV artesunate monotherapy is the standard of care with strong evidence supporting its efficacy and safety. There is no evidence or guideline recommendation supporting dual therapy with IV chloroquine, which could potentially increase risks without adding benefits.