What is the first-line treatment for a patient with falciparum malaria, between artemether (lumefantrine) and artesunate (Artesunate-Sp)?

First-Line Treatment for Falciparum Malaria

For uncomplicated falciparum malaria, artemether-lumefantrine (AL) is the preferred first-line treatment, with artesunate-SP (sulfadoxine-pyrimethamine) not being a recommended artemisinin-based combination therapy in current guidelines. 1

Primary Recommendation: Artemether-Lumefantrine

The 2024 Clinical Microbiology and Infection guidelines explicitly designate artemether-lumefantrine as a preferred first-line treatment for uncomplicated P. falciparum malaria. 1 The regimen consists of:

• Dosing: For patients >35 kg: 4 tablets at H0, 4 tablets at H8 on day 1; then 4 tablets at H36 and H48 on day 2; then 4 tablets at H60 and H72 on day 3 (total 24 tablets over 72 hours). 1

• Administration: Must be taken with a fatty meal or drink to optimize absorption. 1

• Advantages: Rapid onset of action, more rapid parasite clearance compared to non-artemisinin regimens, and reduction in hospital stay. 1

Why Not Artesunate-SP?

Artesunate combined with sulfadoxine-pyrimethamine (SP) is not listed among the recommended artemisinin-based combination therapies in current European and North American guidelines. 1 The guideline-recommended ACTs are:

1. Artemether-lumefantrine (AL) - First-line 1
2. Dihydroartemisinin-piperaquine (DHA-PPQ) - First-line 1
3. Atovaquone-proguanil - Second-line alternative 1

Alternative First-Line Option

Dihydroartemisinin-piperaquine is equally designated as preferred first-line treatment alongside artemether-lumefantrine. 1 This combination offers:

• Dosing: 3 tablets per day for 3 days (36-75 kg) or 4 tablets per day for 3 days (>75 kg). 1
• Administration: Must be taken in fasting condition. 1
• Advantage: Longer half-life of piperaquine provides extended post-treatment prophylaxis. 1

Important Caveats

QTc Prolongation Risk

Both artemether-lumefantrine and dihydroartemisinin-piperaquine can cause QTc interval prolongation. 1 Avoid in patients at risk of QTc prolongation or those taking medications that prolong QTc. 1

Pregnancy Considerations

Artemether-lumefantrine can be used in all trimesters of pregnancy as indicated by WHO and CDC guidelines. 1

Severe Malaria

If the patient has any criteria for severe malaria (parasitemia >2-5%, impaired consciousness, severe anemia, acidosis, hypoglycemia, renal impairment), intravenous artesunate becomes the mandatory first-line treatment at 2.4 mg/kg at 0,12, and 24 hours, then daily. 2, 3 This is a medical emergency requiring ICU admission. 2, 3

Geographic Resistance Patterns

There is established resistance to ACT regimens in the Greater Mekong sub-region, which should influence treatment selection for infections acquired in Southeast Asia. 1

Efficacy Data

Studies in non-endemic settings demonstrate artemether-lumefantrine achieves:

• 98.4% PCR-corrected adequate clinical and parasitological response at day 7. 1
• 96% PCR-corrected cure rate at day 28. 1
• Mean fever clearance time of 36.8 hours. 1