Treatment of Plasmodium falciparum Malaria

First-Line Treatment Options for Uncomplicated P. falciparum Malaria

The World Health Organization recommends artemisinin-based combination therapies (ACTs) as the first-line treatment for uncomplicated Plasmodium falciparum malaria, with artemether-lumefantrine (AL) or dihydroartemisinin-piperaquine (DP) being the preferred options 1, 2, 3
Artemether-lumefantrine (AL) is 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 a fatty meal to enhance absorption 1, 2, 3
Dihydroartemisinin-piperaquine (DP) is administered as 3 tablets daily for 3 days (36-75 kg) or 4 tablets daily for 3 days (>75 kg), and 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

Atovaquone-proguanil is recommended when ACTs are contraindicated, dosed as 4 tablets daily for 3 days (>40 kg), and taken with a fatty meal 1, 2, 3

Quinine sulfate plus doxycycline or clindamycin is an alternative treatment option, with 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

Intravenous artesunate is the 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, with 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

AL can be used in all trimesters of pregnancy as recommended by the World Health Organization and the Centers for Disease Control and Prevention 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

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, hypoglycemia, and potential for serious hematologic reactions including thrombocytopenia 4, 2
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

The World Health Organization recommends intravenous artesunate as the first-line treatment for severe malaria, with a dosing regimen of 2.4 mg/kg IV at 0, 12, and 24 hours, then daily until parasite density is <1% 5
Intravenous artesunate should be initiated immediately as a medical emergency, and once clinically improved, switch to a full course of oral artemisinin-based combination therapy (ACT) 5

The TropNet severe malaria study demonstrated faster parasite clearance time and shorter ICU stay with intravenous artesunate compared to quinine, with a strength of evidence rated as high 5

Exchange blood transfusion is no longer indicated with the availability of artesunate, as recommended by the Clinical Microbiology and Infection guideline 5
Restrictive fluid management should be adopted to avoid pulmonary or cerebral edema, with a strength of evidence rated as moderate 5
Acetaminophen 1 g every 6 hours for 72 hours may provide reno-protective benefit in acute kidney injury, with a strength of evidence rated as low 5