What are the oral and parenteral treatment regimens for Plasmodium (P.) vivax and Plasmodium (P.) falciparum malaria?

Treatment Regimens for Plasmodium vivax and Plasmodium falciparum Malaria

For uncomplicated malaria, chloroquine remains the first-line treatment for P. vivax in chloroquine-sensitive areas, while P. falciparum requires artemisinin-based combination therapies in most regions due to widespread chloroquine resistance. 1

Oral Treatment for P. vivax

First-line Treatment

• Chloroquine (in chloroquine-sensitive areas):
  • Adults: Total dose of 1,500 mg (25 mg/kg) over 3 days - 600 mg, 600 mg, and 300 mg at 0,24, and 48 hours 1
  • Children: 25 mg/kg total over 3 days - 10 mg/kg, 10 mg/kg, and 5 mg/kg at 0,24, and 48 hours 1

Anti-relapse Therapy (Radical Cure)

• Primaquine (to eliminate hypnozoites):
  • Adults: 15 mg daily for 14 days 1
  • Children: 0.3 mg/kg/day for 14 days 1
  • For G6PD deficiency (intermediate 30-70% activity with non-Mediterranean variant): 0.75 mg/kg weekly (maximum 45 mg) for 8 weeks 2

Alternative Regimens for Chloroquine-Resistant P. vivax

• Mefloquine: 1250 mg (five 250 mg tablets) as a single oral dose 3
• Halofantrine: 24 mg base/kg in 12 hours 4

Oral Treatment for P. falciparum

First-line Treatment (Chloroquine-Resistant Areas)

• Artemisinin-based combination therapies (ACTs) such as artemether-lumefantrine 5
• Atovaquone-proguanil combination has shown 100% efficacy in clinical trials 6
• Mefloquine: 1250 mg (five 250 mg tablets) as a single oral dose 3

Parenteral Treatment for Severe Malaria (Both P. vivax and P. falciparum)

First-line Treatment

• Artesunate: 2.4 mg/kg IV at 0,12, and 24 hours, then once daily until oral medication can be taken 1, 5
• Switch to complete course of oral ACT once patient improves 5

Alternative Parenteral Treatment

• Quinidine gluconate (if artesunate unavailable):
  • Loading dose: 10 mg/kg IV over 1-2 hours
  • Maintenance: 0.02 mg/kg/minute infusion for ≥24 hours
  • Treatment duration: 7 days for Southeast Asia/Oceania infections; 3 days for other regions 1, 5
  • PLUS either doxycycline (100 mg orally every 12 hours) or clindamycin (20 mg/kg daily divided into 3 doses) for 7 days 1

Special Considerations

G6PD Testing

• G6PD testing should be performed before administering primaquine 2
• Primaquine is contraindicated in severe G6PD deficiency (<30% activity) or Mediterranean variant (B-) 2
• In populations with high G6PD deficiency prevalence (notably Asians), limit primaquine to 5 days if testing is unavailable 1

Monitoring During Treatment

• For severe malaria, monitor parasitemia every 12 hours until <1%, then every 24 hours until negative 5
• For IV artesunate, monitor for post-artesunate delayed hemolysis at days 7,14,21, and 28 5

Pregnancy Considerations

• Chloroquine is safe during pregnancy for P. vivax 1
• Primaquine is contraindicated in pregnant or breastfeeding women 2
• For severe malaria in pregnancy, IV artesunate is preferred; if quinine is used, monitor carefully for hypoglycemia 1

Common Pitfalls and Caveats

• P. vivax requires anti-relapse therapy with primaquine to prevent relapses from liver hypnozoites 3
• Failure to test for G6PD deficiency before primaquine administration can lead to severe hemolysis 2
• Inadequate dosing or duration of treatment increases risk of recurrence and drug resistance 7, 8
• Early vomiting after oral medication may require re-dosing 3
• Patients who remain symptomatic after 3 days of therapy should have repeat blood smears and consider alternative therapy 1