What is the recommended treatment for Plasmodium vivax malaria?

Treatment of Plasmodium vivax Malaria

For uncomplicated P. vivax malaria in chloroquine-sensitive areas, treat with chloroquine (25 mg/kg total dose over 3 days) plus primaquine (15 mg base daily for 14 days) for radical cure, but you must test for G6PD deficiency before administering primaquine to prevent life-threatening hemolysis. 1

Blood-Stage Treatment (Schizontocidal Therapy)

Chloroquine-Sensitive Areas

First-line treatment: Chloroquine remains the preferred agent where resistance is not documented 1:

• Adults: 1,000 mg salt initially, then 500 mg at 6,24, and 48 hours (total 2,500 mg salt = 1,500 mg base = 25 mg/kg) 1
• Children: 10 mg/kg, 10 mg/kg, and 5 mg/kg at 0,24, and 48 hours respectively 1
• Pregnant women: Use the adult regimen aggressively—chloroquine is safe in all trimesters 1

Chloroquine-Resistant Areas

Chloroquine resistance is now widespread, affecting most P. vivax endemic regions including Papua New Guinea, Indonesia, and other areas 2, 3. In these settings:

Alternative first-line options 1:

• Artemether-lumefantrine (AL): Adults >35 kg receive 4 tablets at 0,8,24,36,48,60, and 72 hours (must take with fatty meal)
• Dihydroartemisinin-piperaquine (DHA-PPQ): Considered equivalent to chloroquine by WHO guidelines
• Atovaquone-proguanil: 4 tablets daily for 3 days in adults >40 kg (with fatty meal)

Clinical pearl: Therapeutic failure rates with chloroquine alone reach 44% by day 14 and 78% by day 28 in resistant areas 4. Halofantrine showed 0% failure at 14 days but is rarely used 4.

Radical Cure (Anti-Relapse Therapy)

Critical consideration: P. vivax forms dormant liver stages (hypnozoites) that cause relapses—blood-stage treatment alone is insufficient 5, 6.

Primaquine Regimens

Standard regimen 1, 5:

• Adults: 30 mg base (2 tablets of 15 mg base) daily for 14 days
• Children: 0.5 mg/kg/day for 14 days
• Must be given concurrently with or after blood-stage treatment 5

Alternative shorter regimen 1, 7:

• 0.5 mg/kg/day for 7 days: May have little or no difference in recurrence compared to standard 14-day course (RR 0.96,95% CI 0.66-1.39), but evidence is low-certainty 7

High-dose regimen 1:

• 1 mg/kg/day for 7 days: Probably has similar efficacy to high-standard 0.5 mg/kg/day for 14 days (RR 1.03,95% CI 0.82-1.30), but may increase serious adverse events (RR 12.03,95% CI 1.57-92.30) 7

Tafenoquine (Single-Dose Alternative)

• 300 mg single dose for radical cure 1
• Not available in Europe; approved in US and Australia
• Requires quantitative G6PD testing (do not use if <70% activity) 1

Critical Safety Considerations

G6PD Deficiency Screening

Mandatory before primaquine administration 1:

• Life-threatening hemolysis can occur with primaquine in G6PD-deficient patients 1
• Asian populations: Have severe G6PD deficiency—limit primaquine to maximum 5 days if G6PD testing unavailable 1
• African variant (A-): Mild deficiency, relatively resistant to severe hemolysis; can use weekly dosing (0.75 mg/kg weekly for 8 weeks) with close monitoring 1
• Mediterranean variant (B-): Very high risk of severe hemolysis—avoid primaquine entirely 1

Contraindications to Primaquine

• Pregnant women: Absolutely contraindicated 1, 5
• Breastfeeding women: Contraindicated unless infant's G6PD status confirmed normal 1
• G6PD deficiency: Contraindicated or requires modified dosing based on variant 1

Treatment Monitoring

Follow-up protocol 1:

• If symptoms persist >3 days after starting chloroquine, repeat thick blood smear 1
• If parasitemia hasn't diminished markedly by day 3, institute alternative therapy 1
• In chloroquine-resistant areas, if symptoms continue 48-72 hours after treatment initiation, switch to second-line agent 1

Severe/Complicated P. vivax

Rare but possible—treat as severe malaria 1:

• Artesunate IV: 2.4 mg/kg at 0,12,24 hours, then daily for 7 days (preferred)
• Quinine dihydrochloride IV: 20 mg salt/kg loading dose over 4 hours, then 10 mg/kg every 8 hours (alternative)
• Switch to oral therapy when able to tolerate and parasitemia <1% 1

Common Pitfalls

1. Forgetting radical cure: Chloroquine alone treats blood stages but allows relapses from liver hypnozoites 5, 6
2. Assuming chloroquine sensitivity: Resistance is now widespread—know your geographic area 2, 3
3. Skipping G6PD testing: This can be fatal in deficient patients receiving primaquine 1
4. Using primaquine in pregnancy: Always contraindicated regardless of G6PD status 1
5. Inadequate primaquine dosing: Subtherapeutic doses lead to relapse 5