How do I treat malaria in a healthy non‑pregnant adult with uncomplicated infection, and what are the recommended regimens for severe malaria, pregnant patients, children, and prophylaxis?

Malaria Treatment Guidelines

Uncomplicated Malaria in Healthy Non-Pregnant Adults

For uncomplicated P. falciparum malaria, artemisinin-based combination therapy (ACT) is the first-line treatment, with artemether-lumefantrine being the preferred regimen: 4 tablets (20mg artemether + 120mg lumefantrine per tablet) twice daily for 3 days, taken with fatty food to enhance absorption. 1

Treatment Options by Species

P. falciparum (chloroquine-resistant areas):

• First-line: Artemether-lumefantrine 4 tablets at 0 hours, 4 tablets at 8 hours on day 1, then 4 tablets twice daily on days 2-3 (total 24 tablets over 72 hours) 1
• Alternative: Dihydroartemisinin-piperaquine 3 tablets once daily for 3 days (taken fasting) 1
• Second-line: Atovaquone-proguanil 4 tablets once daily for 3 days (with fatty meal) 1

P. falciparum (chloroquine-sensitive areas like Haiti):

• Chloroquine 1,500 mg base total dose over 3 days remains an option 2

P. vivax, P. ovale, P. malariae:

• Chloroquine 1,500 mg base (25 mg/kg) over 3 days 3, 4
• Critical: For P. vivax and P. ovale, add primaquine 15 mg daily for 14 days to eradicate liver hypnozoites and prevent relapse 3, 4
• Must perform G6PD testing before primaquine to prevent life-threatening hemolysis 3, 4
• In areas with known chloroquine resistance (Papua New Guinea, Indonesia, Sabah), use ACTs instead 5

Monitoring Uncomplicated Cases

• Check parasitemia on day 3 (expect 75% reduction) and day 7 (expect negative result) 5
• If symptoms persist beyond 3 days, repeat thick blood smear 3, 4
• For patients treated with oral ACTs, monitor for post-artesunate delayed hemolysis (PADH) on days 7 and 14 5

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Severe Malaria

Severe malaria is a medical emergency requiring immediate intravenous artesunate as first-line therapy: 2.4 mg/kg at 0,12, and 24 hours, then once daily until the patient can take oral medication. 5, 1

Criteria for Severe Malaria

• Impaired consciousness or coma 3
• Seizures 3
• Respiratory distress or pulmonary edema 2
• Shock or cardiovascular collapse 2
• Acute kidney injury 2
• Metabolic acidosis 2
• Severe anemia 2
• Hypoglycemia 3
• High parasitemia (>2% in non-immune patients) 3

Treatment Protocol

• IV artesunate 2.4 mg/kg at 0,12,24 hours, then daily until parasitemia <1% and patient can take oral medication 5, 1
• Once stable, switch to full course of oral ACT 5
• If artesunate unavailable: IV quinine 20 mg/kg loading dose over 3 hours, then 10 mg/kg every 12 hours 1
• Exchange transfusion is no longer indicated with availability of artesunate 5

Critical Supportive Care

• Restrictive fluid management to prevent pulmonary and cerebral edema 5
• Monitor and aggressively treat hypoglycemia 3
• Consider acetaminophen 1g every 6 hours for 72 hours for renal protection 5
• Antibiotics only if bacterial co-infection suspected and continued only if cultures positive 5
• Avoid corticosteroids (detrimental in cerebral malaria) 3

Intensive Monitoring

• Parasitemia every 12 hours until <1%, then every 24 hours until negative 5, 1
• Monitor hemoglobin, haptoglobin, and LDH on days 7,14,21, and 28 for PADH 5
• Continuous monitoring of cardiovascular, pulmonary, renal, and metabolic parameters 5

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Pregnant Patients

Pregnant women with malaria require aggressive treatment using standard adult regimens; both chloroquine and quinine are safe during pregnancy. 3

Treatment Approach

• Uncomplicated malaria: Use standard adult chloroquine regimen for chloroquine-sensitive species 3, 4
• Severe malaria: IV artesunate using standard dosing 3
• Monitor carefully for hypoglycemia if receiving IV quinine 3
• Primaquine and tafenoquine are contraindicated during pregnancy 5
• For P. vivax/P. ovale, defer primaquine until after delivery 5

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Children

Dosing Adjustments

• Chloroquine: 25 mg/kg total dose over 3 days 3, 4
• Primaquine: 0.3 mg/kg/day for 14 days (after G6PD testing) 3, 4
• Artemether-lumefantrine: Weight-based dosing (for >35kg, use adult dosing) 1
• IV artesunate: 2.4 mg/kg at same intervals as adults 1

Special Considerations

• Children from non-endemic regions are at highest risk for severe malaria 6
• Monitor closely for hypoglycemia and metabolic acidosis 3

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Malaria Prophylaxis

Key Principles

• All travelers to endemic regions should receive prophylaxis 6
• Selection depends on destination, drug resistance patterns, patient factors, and preferences 2
• In 2017,71.7% of US residents diagnosed with malaria had not taken prophylaxis 2

Common Regimens

• Atovaquone-proguanil: Daily dosing, taken with food 1
• Doxycycline: Daily dosing 2
• Mefloquine: Weekly dosing 2
• Chloroquine: Weekly dosing for chloroquine-sensitive areas 2

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Critical Pitfalls to Avoid

• Never delay treatment while awaiting species identification—if P. falciparum cannot be excluded, treat as falciparum malaria 3
• Do not use primaquine without G6PD testing due to risk of severe hemolysis 3, 4
• Avoid fluid overload in severe malaria (causes pulmonary/cerebral edema) 5
• Do not assume negative initial blood films exclude malaria—repeat testing if clinical suspicion remains 3
• Remember that >80% of US malaria cases are acquired in Africa, predominantly P. falciparum with chloroquine resistance 2
• Artemether-lumefantrine must be taken with fatty food; dihydroartemisinin-piperaquine must be taken fasting 1
• Consider other causes of fever even with positive blood smears (pneumonia, meningitis) 4