Malaria Treatment
For uncomplicated P. falciparum malaria, artemisinin-based combination therapy (ACT) is the first-line treatment, with artemether-lumefantrine or dihydroartemisinin-piperaquine as preferred options; for severe malaria, intravenous artesunate is mandatory. 1, 2
Treatment Algorithm by Disease Severity and Species
Uncomplicated P. falciparum Malaria
First-line options:
Artemether-lumefantrine (AL): Administer 4 tablets at 0 hours, 4 tablets at 8 hours on day 1, then 4 tablets twice daily on days 2 and 3, achieving cure rates of 96-100% 1, 3
Dihydroartemisinin-piperaquine (DP): Give 3 tablets daily for 3 days (36-75 kg) or 4 tablets daily for 3 days (>75 kg), taken while fasting 1, 2
- Superior to artemether-lumefantrine in preventing P. vivax recurrence (RR 0.32,95% CI 0.24-0.43) 2
Second-line option when ACTs contraindicated:
- Atovaquone-proguanil: 4 tablets daily for 3 days (>40 kg), taken with fatty meal, particularly for patients at risk of QTc prolongation or from Southeast Asia with ACT resistance 2, 3
Alternative regimens:
- Quinine sulfate plus doxycycline, clindamycin, or mefloquine for 7 days, though cure rates with 7-day quinine monotherapy are only 80% in multi-drug resistant areas versus >90% with combination therapy 4, 5
Severe Malaria
Immediate treatment protocol:
- Intravenous artesunate: 2.4 mg/kg IV at 0,12, and 24 hours, then daily until parasitemia <1% 1, 2
- Monitor parasitemia every 12 hours until <1%, then every 24 hours until negative 1
- Transition to oral ACT once parasitemia <1% and patient tolerates oral medication 1, 2
- Post-treatment monitoring: Check for delayed hemolysis on days 7,14,21, and 28 after treatment, as it occurs in 37.4% of patients 2, 3
Uncomplicated Non-Falciparum Malaria (P. vivax, P. ovale, P. malariae)
Initial blood schizontocidal treatment:
- Chloroquine-sensitive regions: Chloroquine 25 mg base/kg total dose over 3 days (600 mg, 600 mg, 300 mg at 0,24,48 hours) 2, 3
- Chloroquine-resistant regions: Use ACT (artemether-lumefantrine or dihydroartemisinin-piperaquine), particularly for travelers from Papua New Guinea, Indonesia, and Sabah where chloroquine failure exceeds 10% 2
Radical cure for P. vivax and P. ovale (to eliminate liver hypnozoites):
- Mandatory G6PD testing before administering 8-aminoquinolines to prevent severe hemolysis 1, 2
- Primaquine: Standard dosing reduces first-time relapse risk by 80%; patients with mild-moderate G6PD deficiency (30-70% activity) can receive 45 mg once weekly for 8 weeks 2
- Tafenoquine: Alternative requiring quantitative G6PD >70%, not available outside US/Australia 2
- Both primaquine and tafenoquine are absolutely contraindicated in pregnancy 2
Special Populations
Pregnant Women
Second and third trimesters:
- Artemether-lumefantrine is recommended as first-line treatment, with cure rates of 94.9-100% and no association with congenital malformations, miscarriage, or adverse pregnancy outcomes 6, 2, 3
- Superior tolerability compared to quinine, with significantly lower rates of tinnitus, dizziness, and vomiting 6, 3
First trimester:
- Mefloquine or quinine plus clindamycin are preferred options 6
- When neither option is available, artemether-lumefantrine should be considered 6
Radical cure contraindication:
- Primaquine and tafenoquine are absolutely contraindicated throughout pregnancy due to hemolysis risk 2
Critical Safety Considerations
QTc Prolongation Risk
- Both artemether-lumefantrine and dihydroartemisinin-piperaquine can cause QTc interval prolongation 1, 2
- Avoid in patients at risk for QTc prolongation or taking medications that prolong QTc 1, 2
Geographic Resistance Patterns
- P. falciparum clinically resistant to quinine has been reported in South America, Southeast Asia, and Bangladesh 4, 5
- Chloroquine resistance is widespread in P. falciparum globally except Haiti and limited regions 5