What is the recommended treatment for a patient with a positive peripheral smear for Plasmodium vivax?

Treatment of Plasmodium vivax Malaria

For uncomplicated P. vivax malaria confirmed on peripheral smear, start either chloroquine (in chloroquine-sensitive areas) or an artemisinin-based combination therapy (ACT), and concomitantly initiate an 8-aminoquinoline drug (primaquine or tafenoquine) to eliminate liver hypnozoites and prevent relapse. 1

Blood Stage Treatment (Schizontocidal Therapy)

First-Line Options

Chloroquine remains the treatment of choice in chloroquine-sensitive regions:

• Adults: Total dose of 1,500 mg chloroquine base (approximately 25 mg/kg) over 3 days: 600 mg at 0 hours, 600 mg at 24 hours, and 300 mg at 48 hours 1
• Children: Total dose of 25 mg/kg chloroquine base over 3 days: 10 mg/kg at 0 hours, 10 mg/kg at 24 hours, and 5 mg/kg at 48 hours 1
• Pregnant women: Use the standard adult chloroquine regimen aggressively, as chloroquine is safe during pregnancy 1

Artemisinin-based combination therapies (ACTs) are equally effective alternatives:

• ACTs clear parasites from peripheral blood faster than chloroquine (parasitemia reduction at 24 hours significantly superior) 2
• In areas with confirmed chloroquine resistance (parts of Oceania, Southeast Asia), ACTs are the preferred option 1, 2
• Dihydroartemisinin-piperaquine appears superior to other ACTs (artemether-lumefantrine, artesunate plus sulfadoxine-pyrimethamine) at preventing recurrent parasitemias before day 28 in high transmission settings 2

Monitoring Treatment Response

• Administer the first chloroquine dose when the blood smear is obtained 1
• Patients should return on day 2 for smear results; if positive, continue therapy 1
• If symptoms persist beyond 3 days or parasitemia has not decreased markedly, obtain a repeat thick smear and consider alternative therapy 1

Radical Cure (Hypnozoitocidal Therapy)

Critical Distinction: P. vivax Requires Additional Treatment

Unlike P. malariae (which does not form liver hypnozoites), P. vivax requires primaquine or tafenoquine to prevent relapse from dormant liver stages. 1, 3

Primaquine Regimen

Standard dosing for radical cure:

• Adults: 15 mg base daily for 14 days 1
• Children: 0.3 mg/kg/day for 14 days 1
• Must be started concomitantly with blood stage treatment 1

Critical Safety Precaution: G6PD Testing

G6PD testing is mandatory before administering primaquine, as prolonged administration can cause life-threatening hemolysis in G6PD-deficient patients. 1, 3

In populations with severe G6PD deficiency (notably among Asians):

• Primaquine should not be administered for greater than 5 days 1, 3
• For mild to moderate G6PD deficiency, weekly primaquine can be considered 3
• If G6PD testing is unavailable and the patient is from a high-risk population, do not give primaquine for more than 5 days 1

Common Pitfalls to Avoid

Do Not Confuse P. vivax with P. malariae

• P. malariae does NOT require primaquine (no liver hypnozoites) 3
• P. vivax DOES require primaquine for radical cure 1, 3

Relapse Risk Without Primaquine

• Without hypnozoitocidal therapy, relapse occurs commonly in P. vivax malaria 4
• Thai strains relapse on average within 3 weeks, but this can be suppressed temporarily by slowly eliminated drugs like chloroquine or mefloquine 5
• At least 2 months of follow-up is required to accurately assess relapse/recrudescence rates 5

Post-Treatment Prophylactic Effect

• ACTs with long half-lives (particularly dihydroartemisinin-piperaquine) provide longer post-treatment prophylaxis, with significantly fewer recurrent parasitemias between day 28 and day 63 2
• This prophylactic effect may be clinically important even when primaquine is given 2

Geographic Resistance Patterns

• High-level chloroquine resistance is documented in parts of Oceania and some areas of Southeast Asia 2, 5
• A 2011 trial from Thailand found 9% recurrent parasitemias with chloroquine versus 2% with ACT, suggesting emerging resistance 2
• Sulfadoxine-pyrimethamine shows high-grade resistance (42% treatment failure) in Thailand and should not be used 5

Special Considerations

Double Infection with P. falciparum

• Double infection with P. falciparum and P. vivax is common (affecting at least 25% of patients in some endemic areas) 5
• Cryptic falciparum malaria prevalence is 8-15%, usually manifesting 3-4 weeks following clearance of vivax malaria 5
• In regions coendemic for P. vivax and P. falciparum, a unified ACT treatment policy for malaria of any cause confers the greatest benefit 6

Renal Impairment

• ACTs have been successfully used in patients with pretreatment serum creatinine >2.0 mg/dL (range 2.1-4.3 mg/dL), with 94.4% achieving normal creatinine by day 7 4