Treatment of Uncomplicated Malaria
For uncomplicated malaria, the treatment depends critically on the Plasmodium species and geographic origin of infection, with chloroquine remaining first-line for non-falciparum species and artemisinin-based combination therapy (ACT) preferred for P. falciparum from chloroquine-resistant regions.
Species Identification is Essential
The first step is determining which Plasmodium species is causing infection, as this fundamentally changes treatment approach 1, 2:
- P. falciparum: Requires ACT or alternative regimens due to widespread chloroquine resistance 3
- P. vivax, P. ovale, P. malariae: Generally chloroquine-sensitive, though some P. vivax resistance exists 4, 3
- Mixed infections: Treat as P. falciparum given the risk of severe disease 4
Treatment for Non-Falciparum Malaria (P. malariae, P. vivax, P. ovale)
Chloroquine remains the treatment of choice for chloroquine-sensitive species 1, 2:
Adult Dosing
- Total dose: 1,500 mg chloroquine base over 3 days 5, 1
- Day 0: 600 mg base initially
- Day 1: 600 mg base at 24 hours
- Day 2: 300 mg base at 48 hours
Pediatric Dosing
- Total dose: 25 mg/kg body weight over 3 days 5, 2
- Day 0: 10 mg/kg base
- Day 1: 10 mg/kg base at 24 hours
- Day 2: 5 mg/kg base at 48 hours
Pregnancy
- Use the same adult chloroquine regimen—chloroquine is safe during pregnancy 5, 2
- Quinine is also safe but requires careful monitoring for hypoglycemia 5
Critical Distinction: P. malariae vs. P. vivax/P. ovale
Do NOT add primaquine for P. malariae—it lacks the hypnozoite liver stage and primaquine adds unnecessary hemolysis risk without benefit 1, 2. This is a common pitfall.
For P. vivax or P. ovale only, consider adding primaquine for radical cure (eradication of liver hypnozoites) 5:
- Adults: 15 mg daily for 14 days
- Children: 0.3 mg/kg/day
- Critical caveat: Screen for G6PD deficiency first—primaquine causes life-threatening hemolysis in G6PD-deficient patients, particularly Asians 5
- In populations with severe G6PD deficiency, limit primaquine to maximum 5 days 5
- Contraindicated in pregnancy—use weekly chloroquine prophylaxis until delivery, then consider primaquine 4
Treatment for Uncomplicated P. falciparum Malaria
Geographic Considerations Matter
Most P. falciparum is chloroquine-resistant, including all infections acquired in Africa 3. Chloroquine is only appropriate for infections from known chloroquine-sensitive regions (Haiti, Central America west of Panama Canal) 3.
First-Line Options for Chloroquine-Resistant P. falciparum
Artemisinin-based combination therapy (ACT) is preferred 5, 6, 3:
Artemether-lumefantrine (Riamet/Coartem): 4 tablets at 0 and 8 hours on day 1, then 4 tablets twice daily on days 2-3, taken with fatty food 1, 4
Atovaquone-proguanil (Malarone): Well-tolerated alternative 4, 3
Quinine plus doxycycline: Highly effective but poorly tolerated 4
Hospitalization Requirement
ALL patients with P. falciparum malaria should be admitted for at least 24 hours, as they can deteriorate suddenly early in treatment 4. This is non-negotiable.
Treatment for Severe/Complicated Malaria
Severe malaria is defined by: impaired consciousness, shock, pulmonary edema, acidosis, severe anemia, parasitemia >2%, seizures, renal impairment, or significant bleeding 5, 3.
Intravenous artesunate is first-line therapy for severe malaria and is superior to quinine 5, 3:
- Dosing: 2.4 mg/kg IV at 0,12, and 24 hours, then daily until parasitemia <1% and patient can take oral therapy 5, 6
- Switch to full course of oral ACT once improved 5
- Critical advantage: Faster parasite clearance and shorter ICU stay compared to quinine 5
Alternative: Intravenous Quinine
If artesunate unavailable, use IV quinine 7, 4:
- Requires careful monitoring for hypoglycemia and cardiac effects 5, 7
- Contraindicated in patients with prolonged QT interval 7
Intensive Care Management
Severe malaria requires ICU-level care with management of 5, 8:
- Metabolic acidosis and hypoglycemia monitoring
- Restrictive fluid management to avoid pulmonary/cerebral edema 5
- Renal support if needed
- Seizure management
- Blood transfusion for severe anemia
Monitoring and Follow-Up
For Uncomplicated Malaria
- Administer first chloroquine dose when blood smear is obtained 2
- Patient returns day 2 for smear results; continue therapy if positive 2
- If symptoms persist beyond 3 days, obtain repeat blood smear—alternative therapy needed if parasitemia hasn't markedly diminished 5, 1
For P. falciparum Treated with ACT
- Check parasitemia on day 3 (expect 75% reduction) and day 7 (expect negative result) 5
- Post-artesunate delayed hemolysis (PADH) monitoring is mandatory: Check hemoglobin, haptoglobin, and LDH on days 7,14,21, and 28 5, 6
- PADH occurs in up to 37.4% of patients treated with artesunate 6
Supportive Care
- Antipyretics: Acetaminophen/paracetamol for fever control 5, 2
- Hydration: Increase fluid intake; use ORS for moderate dehydration 5
- Children with high fever: Frequent tepid water sponging 2
Special Populations and Allergies
Renal Impairment
For severe chronic renal impairment: Loading dose of 648 mg quinine, then 324 mg every 12 hours starting 12 hours later 7
Drug Allergies
- Quinine contraindicated in patients with history of thrombocytopenia, HUS/TTP, hemolytic reactions, or hypersensitivity to mefloquine/quinidine 7
- Cross-sensitivity exists between quinine, quinidine, and mefloquine 7
Myasthenia Gravis and Optic Neuritis
Quinine is absolutely contraindicated—it has neuromuscular blocking activity and can exacerbate both conditions 7
Common Pitfalls to Avoid
- Never use primaquine for P. malariae—it adds hemolysis risk without benefit 1, 2
- Never use quinine for nocturnal leg cramps—serious hematologic reactions outweigh any benefit 7
- Never discharge P. falciparum patients immediately—24-hour observation minimum 4
- Never give primaquine without G6PD screening in at-risk populations 5
- Never assume chloroquine works for African P. falciparum—resistance is universal 3
- Never forget PADH monitoring after artesunate treatment 5, 6