What is the recommended treatment for malaria?

Malaria Treatment

First-Line Treatment for Uncomplicated P. falciparum Malaria

Artemisinin-based combination therapies (ACTs) are the first-line treatment for uncomplicated P. falciparum malaria, with artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DP) as the preferred options. 1, 2, 3

Artemether-Lumefantrine (AL)

• Dosing regimen: 4 tablets at hour 0,4 tablets at hour 8 on day 1, then 4 tablets twice daily on days 2 and 3 1, 2, 3
• Critical administration requirement: Must be taken with a fatty meal or drink to ensure adequate absorption—failure to do so results in subtherapeutic drug levels and treatment failure 1, 2, 3
• Efficacy: Cure rates of 96-100% in most settings 3
• Special consideration: Swiss guidelines recommend extending treatment to 5 days (adding four additional doses) in patients with high body weight or suspected malabsorption 4

Dihydroartemisinin-Piperaquine (DP)

• Dosing regimen: 3 tablets daily for 3 days (36-75 kg) or 4 tablets daily for 3 days (>75 kg) 1, 2
• Critical administration requirement: Must be taken while fasting 1, 2
• Comparative efficacy: Superior to AL in preventing P. vivax recurrence over 42 days (RR 0.32,95% CI 0.24-0.43) 4, 5

Second-Line Options

• Atovaquone-proguanil: For patients with contraindications to ACTs (e.g., QTc prolongation risk) or those from Southeast Asia with ACT resistance 4, 3
  • Dosing: 4 tablets daily for 3 days (>40 kg), taken with fatty food 6
• Alternative regimens: Quinine sulfate plus doxycycline, clindamycin, or mefloquine 4

Treatment of Uncomplicated Non-Falciparum Malaria

P. vivax, P. ovale, and P. malariae

• Chloroquine-sensitive regions: Chloroquine is the drug of choice with a total dose of 25 mg base/kg over 3 days 1, 7
  • Adult dosing: 600 mg base at 0 hours, 600 mg base at 24 hours, 300 mg base at 48 hours 7
• Chloroquine-resistant regions: ACTs recommended for travelers from Papua New Guinea, Indonesia, and Sabah where chloroquine failure exceeds 10% 4

Radical Cure for P. vivax and P. ovale

• Essential step: Following blood schizontocidal treatment, primaquine or tafenoquine must be administered to eliminate liver hypnozoites and prevent relapse 1, 2
• Critical safety requirement: Test for G6PD deficiency before administering 8-aminoquinolines—failure to do so can cause severe hemolysis 4, 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 4
• Contraindication: Both primaquine and tafenoquine are contraindicated during pregnancy 4

Treatment of Severe Malaria

Intravenous artesunate is the first-line treatment for all forms of severe malaria. 1, 2, 3

• Dosing: 2.4 mg/kg IV at 0,12, and 24 hours, then daily until parasitemia is <1% 1
• Monitoring: Check parasitemia every 12 hours until <1%, then every 24 hours until negative 2, 3
• Transition to oral therapy: Once patient improves clinically (parasitemia <1%) and can tolerate oral medications, complete treatment with a full course of oral ACT 1, 2, 3
• Post-treatment monitoring: Monitor for post-artemisinin delayed hemolysis (PADH) on days 7,14,21, and 28 after treatment—this occurs in 37.4% of patients using strict definitions 4, 3

Special Populations

Pregnant Women

• First trimester: Mefloquine or quinine plus clindamycin are preferred; however, when neither is available, AL should be considered 4, 2
• Second and third trimesters: AL is recommended as a treatment option based on WHO and CDC endorsement 4, 1, 2
• Evidence basis: Multiple trials and meta-analyses found no association between ACT treatment and congenital malformations or miscarriage in second/third trimester 4

Patients with Renal Impairment

• Atovaquone-proguanil: Should not be used for prophylaxis in severe renal impairment (CrCl <30 mL/min); may be used with caution for treatment only if benefits outweigh risks 6

Critical Pitfalls to Avoid

• Inadequate fat intake with AL: This is the most common cause of treatment failure with artemether-lumefantrine—patients must consume fatty food or drink with each dose 1, 2, 3
• Delayed diagnosis: Delayed treatment of P. falciparum malaria significantly increases mortality 1, 2
• QTc prolongation risk: Both AL and DP can prolong QTc interval and should be avoided in patients at risk or taking QTc-prolonging medications 1, 2, 3
• Failure to test for G6PD deficiency: Not testing before administering primaquine or tafenoquine can lead to life-threatening hemolysis 1, 2
• Underestimating parasitemia: Different thresholds (2-5%) are used to define severe malaria—err on the side of treating as severe if any doubt exists 1