What is the recommended treatment for uncomplicated and severe malaria?

Treatment of Malaria

The recommended treatment for uncomplicated malaria is chloroquine for P. vivax, P. ovale, and P. malariae infections, and artemisinin-based combination therapy (ACT) for P. falciparum infections, while severe malaria requires intravenous artesunate as first-line therapy. 1, 2

Treatment of Uncomplicated Malaria

P. falciparum Malaria

• First-line treatment: Artemisinin-based combination therapy (ACT)

  • Artemether-lumefantrine (AL): 4 tablets at 0,8,24,36,48, and 60 hours with fatty meal 1
  • Dihydroartemisinin-piperaquine (DHA-PPQ): 3 tablets daily for 3 days in fasting condition 1

• Second-line options (for contraindications to ACTs or resistance concerns):

  • Atovaquone-proguanil for patients from Southeast Asia (Greater Mekong sub-region) with high ACT resistance 3
  • Quinine sulphate with doxycycline, clindamycin, or mefloquine 3

Important note: Some studies suggest extending artemether-lumefantrine treatment from 3 to 5 days due to potential treatment failures related to body weight affecting lumefantrine concentration 3

Non-falciparum Malaria (P. vivax, P. ovale, P. malariae)

• First-line treatment: Chloroquine at 25 mg base/kg total dose over 3 days

  • Day 1-2: 10 mg/kg/day
  • Day 3: 5 mg/kg 1

• For chloroquine-resistant P. vivax (from Papua New Guinea, Indonesia, Sabah):

  • ACTs (dihydroartemisinin-piperaquine preferred over artemether-lumefantrine) 3, 1

• Anti-relapse therapy for P. vivax and P. ovale (to prevent relapse from liver hypnozoites):

  • Primaquine: 15-30 mg base daily for 14 days (after G6PD testing)
  • Tafenoquine: Single 300 mg dose (where available, after G6PD testing) 1
  • Reduces relapse risk by approximately 80% 3, 1

Treatment of Severe Malaria

• First-line treatment: Intravenous artesunate 2
• Follow with complete course of oral ACT after patient can tolerate oral medication

Special Considerations

Pregnancy

• Artemether-lumefantrine is now endorsed for uncomplicated malaria in all trimesters of pregnancy 3
• Primaquine and tafenoquine are contraindicated during pregnancy 1
• Anti-relapse therapy should be deferred until after pregnancy 1

Children

• Weight-based dosing required:
  • Artemether-lumefantrine pediatric tablets (62.5 mg/25 mg):
    • 5-8 kg: 2 pediatric tablets × 3 days
    • 9-10 kg: 3 pediatric tablets × 3 days
    • 11-20 kg: 4 pediatric tablets or 1 adult tablet × 3 days 1

G6PD Deficiency

• Mandatory G6PD testing before administering primaquine or tafenoquine 1
• For mild to moderate G6PD deficiency (>30% <70% activity): weekly primaquine (45 mg) for 8 weeks 3

Monitoring and Complications

• Monitor patients for 48-72 hours after initiating treatment 1
• Watch for post-artemisinin delayed hemolysis (PADH) in 1.9-37.4% of patients treated with ACTs 3, 1
• Monitor parasitemia daily until cleared 1
• Consider ECG monitoring for patients on quinine (QT prolongation risk) 1
• Regular blood glucose checks (hypoglycemia risk) 1

Common Pitfalls and Caveats

1. Failure to test for G6PD deficiency before administering primaquine/tafenoquine, risking life-threatening hemolysis 1

2. Inadequate dosing of artemether-lumefantrine in larger patients, potentially leading to treatment failure 3

3. Missing radical cure with primaquine for P. vivax/P. ovale infections, leading to relapse 3, 1

4. Not considering resistance patterns based on geographic acquisition of infection:

   • Chloroquine resistance in P. falciparum is widespread globally, especially in Africa 2
   • Emerging artemisinin resistance in parts of Africa (Rwanda, western Uganda, Horn of Africa) and Southeast Asia 3, 1

5. Inadequate fatty meal with artemether-lumefantrine administration, reducing lumefantrine absorption 3

6. Overlooking drug interactions with commonly used medications like quinine, mefloquine, and ketoconazole 4

By following these evidence-based recommendations and avoiding common pitfalls, clinicians can effectively manage both uncomplicated and severe malaria, reducing morbidity and mortality associated with this potentially life-threatening infection.