What is the role of artesunate (intravenous antimalarial) in the treatment of Plasmodium vivax malaria?

Role of Artesunate in Plasmodium vivax Malaria Treatment

Intravenous artesunate is indicated for severe P. vivax malaria but is not the first-line treatment for uncomplicated P. vivax infections, where chloroquine remains the drug of choice. 1

Treatment Algorithm for P. vivax Malaria

Uncomplicated P. vivax Malaria

1. First-line treatment: Chloroquine

   • Remains the drug of choice for uncomplicated P. vivax infections 1
   • Different dosing regimens available to achieve total dose

2. Alternative treatments (when chloroquine is contraindicated or resistance is suspected):

   • Oral artesunate (5-day course) followed by primaquine 2, 3
   • Artemisinin-based combination therapies (ACTs) such as Artemether-Lumefantrine

3. Radical cure (to prevent relapse):

   • Primaquine (14-day course) to eliminate liver hypnozoites 4, 2
   • High-dose primaquine (0.6 mg/kg/day for 14 days) has shown effectiveness in preventing relapse 2

Severe P. vivax Malaria

1. Intravenous artesunate is indicated at 2.4 mg/kg at 0,12, and 24 hours, then daily until parasitemia is <1% and patient can take oral medication 4

2. Switch to oral therapy once patient improves:

   • Complete treatment with appropriate oral antimalarial
   • Add primaquine for radical cure

Evidence for Artesunate in P. vivax Treatment

Efficacy

• Artesunate demonstrates rapid parasite clearance in P. vivax infections with mean parasite clearance time of 36.7 hours 3
• Fever clearance time with artesunate (14.6 hours) is better than chloroquine 3
• In clinical trials, artesunate showed 100% cure rate at 14 days, though relapses occurred later without primaquine 3
• Artesunate has successfully treated chloroquine-resistant and mefloquine-resistant P. vivax cases 5

Limitations

• When used as monotherapy, artesunate should be continued for 5-7 days to prevent recrudescence 6
• Without primaquine, P. vivax can reappear in 50% of patients treated with artesunate alone 2
• To prevent resistance development, artesunate should never be used alone for P. vivax 3

Monitoring During Treatment

• Check parasitemia every 12 hours until <1%, then every 24 hours until negative 4
• Monitor full blood count, hepatic, kidney, and metabolic parameters daily 4
• Watch for post-artesunate delayed hemolysis (PADH), especially in patients with high initial parasitemia 4

Special Considerations

Resistance Concerns

• While chloroquine remains effective for most P. vivax infections, resistance has been reported in some regions 5
• Artesunate can be effective against chloroquine-resistant P. vivax strains 5
• To prevent resistance development, artesunate should be combined with another effective antimalarial 6, 3

Potential Pitfalls

• Misdiagnosis between P. falciparum and P. vivax can lead to inappropriate treatment 7
• In co-endemic areas, sulfadoxine-pyrimethamine plus artesunate has shown non-inferior efficacy to chloroquine for P. vivax 7
• G6PD deficiency must be checked before administering primaquine to prevent hemolysis 2
• Without primaquine, relapse is common even after successful clearance of blood-stage parasites 2, 3

Artesunate is a valuable treatment option for P. vivax malaria, particularly in severe cases or when chloroquine resistance is suspected, but should be used judiciously and in combination with appropriate partner drugs to prevent resistance development.