What is the treatment for uncomplicated and severe malaria?

Treatment for Uncomplicated and Severe Malaria

For uncomplicated Plasmodium falciparum malaria, artemisinin-based combination therapies (ACTs) are the first-line treatment, specifically artemether-lumefantrine or dihydroartemisinin-piperaquine, while severe malaria requires immediate intravenous artesunate. 1, 2, 3

Treatment of Uncomplicated P. falciparum Malaria

First-Line Options:

• Artemether-lumefantrine (AL): For adults >35 kg, administer 4 tablets at 0 hours, 4 tablets at 8 hours on day 1, then 4 tablets twice daily on days 2 and 3 (total of 24 tablets over 72 hours) 1, 2
• Must be taken with a fatty meal or drink to ensure adequate absorption 1, 2, 4
• Dihydroartemisinin-piperaquine (DP): For adults 36-75 kg, administer 3 tablets daily for 3 days; for >75 kg, 4 tablets daily for 3 days 1, 2
• Must be taken in fasting condition 1, 2

Second-Line Options (when ACTs are contraindicated):

• Atovaquone-proguanil: For adults >40 kg, administer 4 tablets daily for 3 days 1, 2
• Must be taken with a fatty meal 1, 2
• Relatively slow-acting compared to ACTs 1

Third-Line Options:

• Quinine sulfate plus doxycycline: Quinine 750 mg salt (3 tablets) for 3-7 days plus doxycycline 100 mg twice daily for 7 days 1, 2
• Quinine sulfate plus clindamycin: Alternative when doxycycline is contraindicated 1
• Mefloquine: Reserved for when other options are contraindicated; not recommended for infections acquired in Southeast Asia or in patients with neuropsychiatric history 1

Treatment of Uncomplicated Non-falciparum Malaria

• Chloroquine is the drug of choice for P. vivax, P. ovale, and P. malariae in chloroquine-sensitive regions 1, 5
• Total dose: 25 mg base/kg over 3 days (typically 1500 mg total) 5
• For P. vivax and P. ovale, follow blood schizontocidal treatment with primaquine or tafenoquine to prevent relapse by eliminating liver hypnozoites 1, 3
• ACTs can be used for P. vivax in areas with chloroquine resistance (Papua New Guinea, Indonesia, and Sabah) 1

Treatment of Severe Malaria

• Intravenous artesunate is the first-line treatment for all forms of severe malaria 1, 2, 3
• Dosage: 2.4 mg/kg IV at 0,12, and 24 hours, then daily until parasite density is <1% 2
• Once patient improves clinically and can take oral medication, complete treatment with a full course of oral ACT 2, 3
• If IV artesunate is unavailable, IV quinine is the second-line option 2

Special Considerations

• Pregnancy: Artemether-lumefantrine can be used in all trimesters of pregnancy as recommended by WHO and CDC 1, 2, 4
• QTc prolongation: Both AL and DP can cause QTc interval prolongation; avoid in patients at risk of QTc prolongation or taking medications that prolong QTc 1, 2, 4
• Post-artemisinin delayed hemolysis (PADH): Monitor for hemolysis on days 7,14,21, and 28 after treatment, particularly in patients treated for severe malaria 2, 4

Common Pitfalls to Avoid

• Failure to ensure adequate fat intake with AL administration can result in subtherapeutic drug levels and treatment failure 2, 4
• Delayed diagnosis and treatment of P. falciparum malaria significantly increases mortality 2, 6
• Underestimating parasitemia levels; different guidelines use thresholds between 2% and 5% to define severe malaria 1
• Not testing for G6PD deficiency before administering primaquine or tafenoquine for radical cure of P. vivax or P. ovale 1, 3
• Not recognizing emerging resistance patterns, particularly in the Greater Mekong sub-region for ACTs and in Southeast Asia for quinine 1, 2