What is the first-line treatment for malaria?

First-Line Treatment for Malaria

Artemisinin-based combination therapy (ACT) is the first-line treatment for uncomplicated Plasmodium falciparum malaria, while chloroquine is the drug of choice for P. vivax, P. ovale, and P. malariae infections, and intravenous artesunate is the first-line treatment for severe malaria. 1

Treatment by Malaria Species

P. falciparum (Uncomplicated)

• First-line: Artemisinin-based combination therapy (ACT)
  • Options include:
    • Artemether-lumefantrine
    • Dihydroartemisinin-piperaquine
    • Artesunate-mefloquine
  • ACTs have demonstrated efficacy exceeding 95% in most regions 1, 2
  • Recent studies in Tanzania showed PCR-corrected adequate clinical and parasitological response rates of 97.6-100% with artemether-lumefantrine 3

P. vivax, P. ovale, P. malariae

• First-line: Chloroquine (25 mg base/kg over 3 days) 4, 1
• For chloroquine-resistant P. vivax (from Papua New Guinea, Indonesia, Sabah):
  • ACTs are recommended, with dihydroartemisinin-piperaquine preferred over artemether-lumefantrine 1
  • Meta-analysis shows superiority of dihydroartemisinin-piperaquine over chloroquine for P. vivax 4

Severe Malaria (Any Species)

• First-line: Intravenous artesunate 4, 1
  • Recommended by WHO for all forms of severe malaria
  • Demonstrated faster parasite clearance time and shorter ICU stays compared to quinine 4
  • Once patient improves (parasitemia <1%) and can take oral medication, switch to a complete course of ACT 4

Anti-Relapse Therapy for P. vivax and P. ovale

• Required additional treatment: Primaquine or tafenoquine to eliminate liver hypnozoites 4, 1
  • Primaquine: 15-30 mg base daily for 14 days (after G6PD testing)
  • Tafenoquine: Single 300 mg dose (where available, after G6PD testing)
  • Primaquine reduces relapse risk by approximately 80% 4, 1

Important Considerations

G6PD Testing

• Mandatory before administering primaquine or tafenoquine due to risk of hemolysis in G6PD-deficient patients 1
• For patients with mild to moderate G6PD deficiency (30-70% activity), primaquine can be given at 45 mg once weekly for 8 weeks 4

Resistance Patterns

• P. falciparum has developed resistance to chloroquine in most regions worldwide, including Africa 5
• Emerging artemisinin resistance in Greater Mekong sub-region and parts of Africa (Rwanda, western Uganda, Horn of Africa) 1
• For travelers from Southeast Asia (Greater Mekong sub-region) with high ACT resistance, atovaquone-proguanil is recommended as a second-line option 1

Special Populations

• Pregnancy:
  • Artemether-lumefantrine is now endorsed for uncomplicated malaria in all trimesters 1
  • Primaquine and tafenoquine are contraindicated during pregnancy 4, 1
• Children:
  • Weight-based dosing required
  • For artemether-lumefantrine: specific pediatric dosing charts available 1

Monitoring and Follow-Up

• Monitor parasitemia daily until cleared 1
• Watch for post-artemisinin delayed hemolysis (PADH) in 1.9-37.4% of patients treated with ACTs 1
• For severe malaria, restrictive fluid management is generally adopted to avoid pulmonary or cerebral edema 4

Common Pitfalls to Avoid

1. Not considering geographic resistance patterns when selecting treatment
2. Inadequate dosing of artemether-lumefantrine in larger patients
3. Failing to administer primaquine for radical cure of P. vivax/P. ovale
4. Not administering artemether-lumefantrine with food (reduces lumefantrine absorption)
5. Skipping G6PD testing before administering primaquine or tafenoquine
6. Delaying treatment of severe malaria (medical emergency requiring immediate IV artesunate)

The choice of ACT should be guided by local resistance patterns, with artemether-lumefantrine and dihydroartemisinin-piperaquine showing excellent efficacy in most regions 6. Dihydroartemisinin-piperaquine has demonstrated superior efficacy compared to other ACTs in some studies and provides better protection against P. vivax recurrence 6.