What is the recommended treatment for malaria?

Recommended Treatment for Malaria

The first-line treatment for uncomplicated Plasmodium falciparum malaria is artemisinin-based combination therapy (ACT), specifically artemether-lumefantrine or dihydroartemisinin-piperaquine, while chloroquine remains the drug of choice for non-falciparum species in chloroquine-sensitive regions, followed by primaquine for P. vivax and P. ovale to prevent relapse. 1, 2, 3

Treatment Based on Plasmodium Species

P. falciparum (Uncomplicated)

• Artemether-lumefantrine (AL) is recommended as first-line treatment with dosing of 4 tablets at 0 hours, 4 tablets at 8 hours on day 1, then 4 tablets twice daily on days 2 and 3 1, 2
• AL must be taken with fatty food to enhance absorption, as inadequate fat intake can result in subtherapeutic drug levels and treatment failure 2, 3
• Dihydroartemisinin-piperaquine (DP) is an effective alternative first-line ACT, dosed as 3 tablets daily for 3 days (36-75 kg) or 4 tablets daily for 3 days (>75 kg), taken in fasting condition 1, 2
• For patients in whom ACTs are contraindicated (e.g., risk of QT prolongation), atovaquone-proguanil is recommended as second-line treatment 4, 2

P. vivax and P. ovale

• Chloroquine is the drug of choice for uncomplicated P. vivax malaria in chloroquine-sensitive regions 4, 3
• The chloroquine dosing regimen is: total dose of 25 mg base/kg over 3 days (600 mg, 600 mg, and 300 mg base at 0,24, and 48 hours) 5
• ACTs are also effective for P. vivax and should be considered for patients from areas with known chloroquine resistance (Papua New Guinea, Indonesia, and Sabah) 4, 3
• Following blood schizontocidal treatment, patients with P. vivax or P. ovale require primaquine to eliminate liver hypnozoites and prevent relapse 4, 3
• G6PD testing is mandatory before administering primaquine due to risk of hemolysis in G6PD-deficient patients 4, 1

P. malariae and P. knowlesi

• Chloroquine or ACTs are effective for these species 1, 6

Treatment for Severe Malaria

• For severe malaria (any species), intravenous artesunate is the first-line treatment at a dose of 2.4 mg/kg IV at 0,12, and 24 hours, then continued daily until parasite density is <1% 1, 2
• Once the patient improves clinically (parasitemia <1%) and can take oral medication, treatment should be completed with a full course of oral ACT 1, 2
• Post-artemisinin delayed hemolysis (PADH) is a potential adverse effect that requires monitoring on days 7,14,21, and 28 after treatment 1, 3

Special Populations

Pregnant Women

• Artemether-lumefantrine can be used in all trimesters of pregnancy as recommended by the WHO and CDC 4, 3
• For first trimester, when other options are unavailable, quinine plus clindamycin may be considered 1

G6PD Deficient Patients

• For patients with mild to moderate G6PD deficiency (>30% <70% activity), primaquine can be given at 45 mg once weekly for 8 weeks instead of daily dosing 4

Common Pitfalls and Caveats

• Failure to ensure adequate fat intake with artemether-lumefantrine administration can result in subtherapeutic drug levels and treatment failure 2, 3
• Both artemether-lumefantrine and dihydroartemisinin-piperaquine can cause QTc interval prolongation and should be avoided in patients at risk for QTc prolongation or taking medications that prolong QTc 1, 2
• Delayed diagnosis and treatment of P. falciparum malaria is associated with increased mortality 2, 6
• Mefloquine should not be used in patients with active depression, anxiety disorders, psychosis, schizophrenia or other major psychiatric disorders due to risk of neuropsychiatric adverse reactions 7
• Resistance patterns are evolving, with artemisinin partial resistance reported in Africa (Rwanda, western Uganda, and Horn of Africa), requiring vigilance in treatment selection 4