Recommended Treatment for Malaria
The recommended first-line treatment for uncomplicated Plasmodium falciparum malaria is artemisinin-based combination therapy (ACT), specifically artemether-lumefantrine (AL) or dihydroartemisinin-piperaquine (DP), with the choice depending on regional resistance patterns and patient factors. 1, 2, 3
Treatment Based on Plasmodium Species
For P. falciparum (Uncomplicated):
- Artemether-lumefantrine (AL) is the primary first-line treatment, dosed as 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, 3
- AL must be taken with fatty food to enhance absorption and prevent treatment failure 2, 3
- Dihydroartemisinin-piperaquine (DP) is an effective alternative, dosed as 3 tablets daily for 3 days (36-75 kg) or 4 tablets daily for 3 days (>75 kg), taken while fasting 1, 2
- For patients with contraindications to ACTs (e.g., QT prolongation risk), atovaquone-proguanil is recommended as second-line treatment 4, 2, 5
For P. vivax or P. ovale:
- Initial treatment with ACT or chloroquine (in chloroquine-sensitive regions) 4, 1, 2
- Chloroquine dosing for adults: 600 mg base initially, followed by 300 mg base at 6,24, and 48 hours (total dose 1,500 mg base) 6
- Must be followed by radical cure with primaquine or tafenoquine to eliminate liver hypnozoites and prevent relapse 4, 1, 2
- G6PD testing is required before administering primaquine or tafenoquine due to risk of hemolysis 4, 1
For P. malariae and P. knowlesi:
- Chloroquine is effective in regions without resistance 2, 7
- ACTs are also effective and may be used for simplification of treatment 4
Treatment for Severe Malaria
- Intravenous artesunate is the first-line treatment for severe malaria of any species 1, 3, 7
- Monitor parasitemia every 12 hours until <1%, then every 24 hours until negative 1, 3
- Once the patient improves clinically (parasitemia <1%) and can take oral medication, complete treatment with a full course of oral ACT 1, 3
- Post-treatment monitoring should include checking for delayed hemolysis on days 7,14,21, and 28 1, 2
Special Populations
Pregnant Women:
- Artemether-lumefantrine can now be used in all trimesters of pregnancy as recommended by WHO and CDC 4, 2
- In first trimester, if other options unavailable, quinine plus clindamycin may be considered 1
Children:
- Dosing should be weight-based 6
- Neuropsychiatric symptoms can be difficult to identify in children, requiring vigilant monitoring 8
Common Pitfalls and Caveats
- Failure to ensure adequate fat intake with artemether-lumefantrine can result in subtherapeutic drug levels and treatment failure 1, 2, 3
- Post-artemisinin delayed hemolysis (PADH) can occur in up to 37.4% of patients and requires monitoring 4, 2
- Both artemether-lumefantrine and dihydroartemisinin-piperaquine can cause QTc interval prolongation and should be avoided in patients at risk for QTc prolongation 1, 2, 3
- Delayed diagnosis and treatment of P. falciparum malaria is associated with increased mortality 1, 3
- In areas with emerging artemisinin resistance (Rwanda, western Uganda, Horn of Africa, Southeast Asia), treatment failures may occur and extended treatment regimens or alternative therapies may be needed 4, 7
Efficacy of Recommended Treatments
- ACTs provide rapid parasite clearance with fever clearance times around 36.8 hours and parasite clearance times around 41.5 hours 3, 9
- Clinical and parasitological response rates exceed 95% for artemether-lumefantrine (six-dose regimen), dihydroartemisinin-piperaquine, and artesunate-mefloquine 9, 10
- The four-dose regimen of artemether-lumefantrine shows slightly lower efficacy (96.4%) compared to the recommended six-dose regimen 9