Malaria Treatment Guidelines

First-Line Treatment Options

The World Health Organization recommends artemether-lumefantrina (AL) as the first-line treatment for uncomplicated P. falciparum malaria, with cure rates of 96-100% 1, 2
The dosage of AL is 4 tablets at hour 0, 4 tablets at hour 8 on day 1, then 4 tablets twice a day on days 2 and 3, and should be taken with a fatty meal or drink to improve absorption 1, 3
Dihydroartemisinin-piperazine (DP) is an effective alternative as first-line therapy, administered as 3 tablets per day for 3 days (36-75 kg) or 4 tablets per day for 3 days (>75 kg), to be taken on an empty stomach 1, 2

For patients in whom ACTs are contraindicated (e.g., risk of QTc prolongation), atovaquone-proguanil is recommended as a second-line treatment, with a dosage of 4 tablets per day for 3 days (>40 kg), to be taken with a fatty meal 2

For severe P. falciparum malaria, the first-line treatment is intravenous artesunate, with monitoring of parasitemia every 12 hours until <1%, then every 24 hours until negative 3, 2
Once the patient improves clinically (parasitemia <1%) and can take oral medications, treatment should be completed with a full course of oral ACT 3, 2

For pregnant women, artemether-lumefantrina can be used in all trimesters of pregnancy as indicated by the WHO and CDC 1, 2
For P. vivax or P. ovale malaria, initial treatment with ACT or chloroquine (in chloroquine-sensitive regions) should be followed by radical cure with primaquine to eliminate hepatic hypnozoites and prevent relapses 2, 4
In areas without chloroquine resistance, the oral chloroquine regimen for treating uncomplicated malaria attacks is: adults - total dose of 1,500 mg of chloroquine (approximately 25 mg/kg of body weight) administered over a period of 3 days (600 mg, 600 mg, and 300 mg at 0, 24, and 48 hours) 4

Failing to take AL with a fatty meal can lead to subtherapeutic drug levels and treatment failure 1, 3
Delayed diagnosis and treatment of P. falciparum malaria are associated with increased mortality 2
Both artemether-lumefantrina and dihydroartemisinin-piperazine can cause QTc prolongation and should be avoided in patients at risk of QTc prolongation or taking medications that prolong the QTc 1, 3
It is necessary to monitor for delayed hemolysis after artemisinin-based treatment (PADH), particularly on days 7, 14, 21, and 28 after treatment 1, 2

The Centers for Disease Control and Prevention recommends artemether-lumefantrine as the first-line treatment for uncomplicated malaria in the third trimester of pregnancy, with cure rates ranging from 94.9% to 100% 5, 6, 7
Artemether-lumefantrine performs equal to or better than quinine-based regimens, with a pooled risk ratio of treatment failure of 0.41 (95% CI 0.16-1.06) compared to non-ACTs 5, 8
Despite initial concerns about reduced lumefantrine bioavailability in pregnancy, treatment efficacy remains high at standard non-pregnant dosing 5, 8

No differences in pregnancy outcomes (miscarriage, stillbirth, preterm birth, low birth weight, or congenital abnormalities) were identified when comparing artemether-lumefantrine to quinine-based regimens 9, 10
Meta-analyses of women treated in the second and third trimesters found no association between ACT treatment and adverse pregnancy outcomes 11
Artemether-lumefantrine has superior tolerability compared to quinine, with significantly lower rates of tinnitus, dizziness, and vomiting 11

Quinine 10 mg/kg every 8 hours for 7 days remains an option for patients in whom ACTs are contraindicated, though with inferior tolerability 5, 6

The Centers for Disease Control and Prevention formally updated its recommendations in 2018 to include artemether-lumefantrine as an additional treatment option for uncomplicated malaria in pregnant women during the second and third trimesters, based on the strength and quality of accumulated evidence 11