What is the recommended treatment for malaria?

Malaria Treatment

For uncomplicated P. falciparum malaria, artemether-lumefantrine is the first-line treatment, administered as 4 tablets at 0 hours, 4 tablets at 8 hours on day 1, then 4 tablets twice daily on days 2 and 3, and must be taken with fatty food to ensure adequate absorption. 1, 2

Treatment Algorithm Based on Plasmodium Species and Disease Severity

Uncomplicated P. falciparum Malaria

First-line options:

• Artemether-lumefantrine (AL): 4 tablets at hour 0,4 tablets at hour 8 on day 1, then 4 tablets twice daily on days 2 and 3, with cure rates of 96-100% 1, 3
• Critical administration requirement: AL must be taken with a fatty meal or drink to enhance absorption; failure to do so results in subtherapeutic drug levels and treatment failure 1, 2, 3
• Dihydroartemisinin-piperaquine (DP): 3 tablets daily for 3 days (36-75 kg) or 4 tablets daily for 3 days (>75 kg), taken while fasting 1, 2

Second-line option:

• Atovaquone-proguanil: 4 tablets daily for 3 days (>40 kg), taken with a fatty meal, recommended when ACTs are contraindicated 2, 3

Alternative regimens:

• Quinine sulfate plus doxycycline, clindamycin, or mefloquine for patients with contraindications to ACTs 2
• In chloroquine-sensitive regions (e.g., Haiti), chloroquine remains an option: 600 mg at 0 hours, 600 mg at 24 hours, and 300 mg at 48 hours 3, 4

Severe Malaria

• Intravenous artesunate is the first-line treatment: 2.4 mg/kg IV at 0,12, and 24 hours, then daily until parasitemia is <1% 1, 2, 3
• Monitor parasitemia: Check every 12 hours until <1%, then every 24 hours until negative 1, 3
• Transition to oral therapy: Once parasitemia is <1% and patient can tolerate oral medication, complete treatment with a full course of oral ACT 1, 2
• Post-treatment monitoring: Check for post-artemisinin delayed hemolysis (PADH) on days 7,14,21, and 28, as it occurs in 37.4% of patients 2, 3

Uncomplicated P. vivax, P. ovale, or P. malariae

• Initial treatment: ACT or chloroquine (in chloroquine-sensitive regions) at 600 mg, 600 mg, and 300 mg at 0,24, and 48 hours 1, 3
• Radical cure required for P. vivax and P. ovale: Follow with primaquine or tafenoquine to eliminate liver hypnozoites and prevent relapse 1, 2
• Critical safety step: Test for G6PD deficiency before administering primaquine or tafenoquine to prevent severe hemolysis 1, 2
• Modified dosing for G6PD deficiency: Patients with mild to moderate G6PD deficiency (30-70% activity) can receive primaquine 45 mg once weekly for 8 weeks 2

Special Populations

Pregnant Women

• Second and third trimesters: Artemether-lumefantrine is recommended at the same doses as non-pregnant women 5, 1, 2
• First trimester: Mefloquine or quinine plus clindamycin are preferred options 5
• When other options unavailable: AL should be considered for first trimester treatment 5
• Safety evidence: Multiple trials and meta-analyses found no association between ACT treatment and congenital malformations or miscarriage in second/third trimester 2
• Contraindication: Both primaquine and tafenoquine are contraindicated during pregnancy 2

Critical Pitfalls to Avoid

• Inadequate fat intake with AL: This is the most common cause of treatment failure with artemether-lumefantrine, resulting in subtherapeutic drug levels 1, 2, 3
• Delayed diagnosis: Delayed diagnosis and treatment of P. falciparum malaria significantly increases mortality 1, 2, 3
• QTc prolongation risk: Both AL and DP can cause QTc interval prolongation and should be avoided in patients at risk or taking medications that prolong QTc 1, 2, 3
• Skipping G6PD testing: Not testing for G6PD deficiency before administering primaquine or tafenoquine can lead to severe hemolytic reactions 1, 2
• Incomplete treatment of P. vivax/P. ovale: Failure to provide radical cure with 8-aminoquinolines results in relapse from dormant liver hypnozoites 1, 2

Geographic Considerations

• Chloroquine resistance: P. falciparum has developed chloroquine resistance in most regions worldwide, including Africa; ACTs are required in these areas 4
• Quinine resistance: Clinically resistant P. falciparum to quinine has been reported in some areas of South America, Southeast Asia, and Bangladesh 6
• Multi-drug resistance regions: In Southeast Asia, 7-day quinine monotherapy achieves at least 80% cure rates, while combination therapy with tetracycline or clindamycin achieves >90% cure rates 6