Treatment of Uncomplicated Malaria
For uncomplicated malaria, artemisinin-based combination therapy (ACT) is the first-line treatment, with artemether-lumefantrine being the preferred regimen for P. falciparum malaria, achieving cure rates of 96-100%. 1, 2
Species-Specific Treatment Approach
Plasmodium falciparum (Chloroquine-Resistant Regions)
First-line options include:
Artemether-lumefantrine (AL): 4 tablets at 0 hours, 4 tablets at 8 hours on day 1, then 4 tablets twice daily on days 2-3 1
Atovaquone-proguanil: 4 tablets daily for 3 days (patients >40 kg), taken with fatty meal 1
- Reserved for patients with contraindications to ACTs 1
Quinine-based regimen: 648 mg every 8 hours for 7 days, combined with doxycycline or clindamycin 3, 4
Plasmodium vivax, P. ovale, P. malariae (Chloroquine-Sensitive Regions)
Chloroquine remains first-line treatment:
- Dosing: 1000 mg salt initially, then 500 mg at 6,24, and 48 hours (total 2500 mg over 3 days) 1, 4
- Safe during pregnancy 5
Mandatory radical cure for P. vivax and P. ovale:
- Primaquine: 30 mg base (15 mg salt) daily for 14 days to eliminate liver hypnozoites 5, 1
- Absolutely requires G6PD testing before administration 1, 2
- In severe G6PD deficiency (particularly Mediterranean variant), primaquine causes life-threatening hemolysis 5, 1
- For Asian populations with severe G6PD deficiency, do not administer for >5 days 5
- Contraindicated in pregnancy and breastfeeding 1, 2
Special Population Considerations
Pregnant Women
- ACTs (artemether-lumefantrine) are safe in all trimesters with cure rates of 94.9-100% and no increased adverse pregnancy outcomes 1, 2
- Chloroquine is safe for non-falciparum species 5
- Quinine is safe but requires careful monitoring for hypoglycemia 5
- Primaquine and tafenoquine are absolutely contraindicated 1, 2
- For P. vivax/P. ovale in pregnancy: treat with chloroquine, then weekly chloroquine prophylaxis until delivery, followed by primaquine postpartum 4
Children
- Same regimens as adults with weight-based dosing 5
- Chloroquine: 25 mg/kg total dose over 3 days (10 mg/kg, 10 mg/kg, 5 mg/kg at 0,24,48 hours) 5
- Primaquine: 0.3 mg/kg/day for 14 days 5
- Doxycycline contraindicated in children <12 years; substitute clindamycin 4
Renal Impairment
- Severe chronic renal impairment: Loading dose of 648 mg quinine, then 324 mg every 12 hours starting 12 hours after loading dose 3
Critical Monitoring Requirements
Post-treatment surveillance:
- Monitor for post-artemisinin delayed hemolysis (PADH) on days 7,14,21, and 28 after ACT treatment (occurs in 37.4% using strict definitions) 5, 1
- Check hemoglobin, haptoglobin, and lactate dehydrogenase levels 5
- Parasitemia monitoring: Day 3 (expect 75% reduction) and Day 7 (expect negative result) 5
Baseline assessments:
- QTc interval before quinine or ACT administration (both cause QT prolongation) 1, 3
- G6PD testing mandatory before primaquine 1, 2
Common Pitfalls to Avoid
- Failing to ensure fatty food intake with artemether-lumefantrine is the most common cause of treatment failure 1
- Not testing for G6PD deficiency before primaquine can cause fatal hemolysis, particularly in Asian and Mediterranean populations 5, 1
- Using quinine for nocturnal leg cramps causes serious hematologic reactions including thrombocytopenia and HUS/TTP; this indication is contraindicated 3
- Assuming all fever is malaria in endemic areas—consider pneumonia, meningitis, and other bacterial infections 5
- Forgetting radical cure for P. vivax/P. ovale leads to relapse from dormant liver hypnozoites 1, 2, 4
When to Hospitalize
All patients with P. falciparum malaria should be admitted for at least 24 hours as they can deteriorate suddenly, especially early in treatment 4