What is the recommended treatment for Plasmodium (P.) vivax malaria?

Treatment of Plasmodium vivax Malaria

The recommended treatment for P. vivax malaria consists of chloroquine as the first-line blood schizontocidal agent followed by primaquine for radical cure to prevent relapses, with G6PD testing required before primaquine administration. 1, 2

Initial Treatment (Blood Stage)

• Chloroquine phosphate is the drug of choice for uncomplicated P. vivax malaria at a total dose of 25 mg base/kg administered over 3 days 3, 2
• Artemisinin-based combination therapies (ACTs) should be used instead of chloroquine for patients from areas with known chloroquine resistance (Papua New Guinea, Indonesia, and Sabah) where failure rates exceed 10% 3, 1
• Dihydroartemisinin-piperaquine is preferred among ACTs due to its longer half-life and demonstrated superiority over chloroquine (HR 2.33 at day >42-63) in treating uncomplicated P. vivax malaria 3
• For severe P. vivax malaria (uncommon but possible), intravenous artesunate is the first-line treatment at 2.4 mg/kg IV at 0,12, and 24 hours, then daily until clinical improvement 1

Anti-Relapse Treatment (Liver Stage)

• Primaquine must be administered following blood schizontocidal treatment to eradicate liver hypnozoites and prevent relapses 3, 4
• G6PD testing is mandatory before primaquine administration to prevent hemolysis in G6PD-deficient patients 3, 1
• For G6PD-normal patients, primaquine should be given at 30 mg base daily for 14 days 1
• For patients with mild to moderate G6PD deficiency (>30% but <70% activity), primaquine can be given at 45 mg once weekly for 8 weeks 3
• Primaquine should be administered concurrently with chloroquine as this boosts primaquine blood levels, enhancing its efficacy 3
• Both primaquine and tafenoquine (an alternative 8-aminoquinoline) are contraindicated during pregnancy 3

Special Considerations

• Without anti-relapse therapy, P. vivax can cause relapses due to persistent liver hypnozoites, with a retrospective study showing first-time relapse in 9.3% of P. vivax episodes 3
• Patients prescribed primaquine for P. vivax malaria had an 80% risk reduction of relapse compared to those who did not receive it 3
• Monitor for clinical improvement within 48 hours of starting treatment and obtain follow-up blood smears to confirm parasite clearance 1
• For patients on primaquine, monitor for signs of hemolysis such as dark urine, jaundice, and fatigue, especially in those with partial G6PD deficiency 1
• Despite being historically described as "benign tertian malaria," P. vivax can cause significant morbidity including severe anemia, acute lung injury, and acute kidney injury, particularly in the presence of comorbidities or in recurrent infections 5

Treatment Algorithm

1. Confirm P. vivax infection through microscopy or rapid diagnostic test
2. Test for G6PD deficiency before initiating treatment
3. Assess for severity criteria (respiratory distress, severe anemia, impaired consciousness)
4. For uncomplicated malaria:
   • If from non-resistant area: Chloroquine 25 mg base/kg over 3 days
   • If from resistant area: Dihydroartemisinin-piperaquine or other ACT
5. For severe malaria: IV artesunate followed by complete course of oral therapy when improved
6. Add anti-relapse therapy based on G6PD status:
   • Normal G6PD: Primaquine 30 mg daily for 14 days
   • Mild-moderate deficiency: Primaquine 45 mg weekly for 8 weeks
   • Severe deficiency: Avoid primaquine; consider close monitoring for relapses

The combination of effective blood schizontocidal and anti-hypnozoite treatment is essential to prevent the significant morbidity associated with recurrent P. vivax infections 6, 7.