What is the recommended treatment for Plasmodium (P) falciparum malaria?

Treatment of Plasmodium falciparum Malaria

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

First-Line Treatment Options for Uncomplicated P. falciparum Malaria

• Artemether-lumefantrine (AL): 4 tablets at 0 hours, 4 tablets at 8 hours on day 1, then 4 tablets twice daily on days 2 and 3, must be taken with a fatty meal to enhance absorption 1, 2, 3
• Dihydroartemisinin-piperaquine (DP): 3 tablets daily for 3 days (36-75 kg) or 4 tablets daily for 3 days (>75 kg), must be taken in fasting condition 1, 2, 3
• Both AL and DP demonstrate high efficacy with cure rates of 96-98.4% for uncomplicated falciparum malaria 2, 3

Second-Line Treatment Options

• Atovaquone-proguanil: Recommended when ACTs are contraindicated (e.g., risk of QTc prolongation), dosed as 4 tablets daily for 3 days (>40 kg), taken with a fatty meal 1, 2, 3

Third-Line Treatment Options

• Quinine sulfate plus doxycycline or clindamycin: Quinine 3 tablets (750 mg salt) for 3-7 days plus doxycycline 100 mg twice daily for 7 days, or plus clindamycin 20 mg/kg every 8 hours for 7 days 4, 1
• Quinine should be taken with food to minimize gastric upset 5
• For adults with uncomplicated P. falciparum malaria, quinine dosage is 648 mg orally every 8 hours for 7 days 5

Treatment for Severe P. falciparum Malaria

• Intravenous artesunate: First-line treatment at 2.4 mg/kg IV at 0,12, and 24 hours, then daily until parasite density is <1% 4, 2, 3
• Once the 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: 20 mg salt/kg over 4 hours (loading dose) followed by 10 mg/kg over 4 hours starting 8 hours after initiation and then every 8 hours 4, 2

Special Considerations

• AL can be used in all trimesters of pregnancy as recommended by WHO and CDC 1, 3
• Both AL and DP can cause QTc interval prolongation and should be avoided in patients at risk for QTc prolongation or taking medications that prolong QTc 1, 2, 3
• Monitor for post-artemisinin delayed hemolysis (PADH), particularly on days 7,14,21, and 28 after treatment 1, 2, 3

Common Pitfalls to Avoid

• Failure to ensure adequate fat intake with AL administration can result in subtherapeutic drug levels and treatment failure 1, 2, 3
• Delayed diagnosis and treatment of P. falciparum malaria is associated with increased mortality 2
• Quinine has significant adverse effects including cinchonism (tinnitus, vertigo, headache), hypoglycemia, and potential for serious hematologic reactions including thrombocytopenia 4, 2, 5
• Quinine should not be used against P. falciparum acquired in Southeast Asia due to resistance concerns 4
• Quinine should be avoided in patients with a history of neuropsychiatric disorders 4

Regional Considerations

• In areas with documented artemisinin resistance (particularly western Cambodia), closely monitor parasite clearance times and consider alternative regimens if available 6
• In areas where P. vivax co-infection is common, ACTs with longer half-lives (like DP) may provide better protection against early relapse 7, 8