What is the treatment for malaria?

Treatment of Malaria

Artemisinin-based combination therapies (ACTs) are the first-line treatment for uncomplicated P. falciparum malaria, with artemether-lumefantrine or dihydroartemisinin-piperaquine as preferred options, while severe malaria requires immediate intravenous artesunate. 1

Uncomplicated P. falciparum Malaria

For patients able to take oral medications and without severe disease criteria, initiate oral ACT immediately:

• Artemether-lumefantrine (AL): 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

  • Critical administration requirement: Must be taken with fatty food or drink to ensure adequate absorption 2, 3
  • Failure to consume adequate fat results in subtherapeutic drug levels and treatment failure 2, 4
  • Cure rates of 96-100% when properly administered 4

• Dihydroartemisinin-piperaquine (DP): 3 tablets daily for 3 days (36-75 kg) or 4 tablets daily for 3 days (>75 kg) 1, 2

  • Must be taken while fasting 3
  • Superior efficacy for P. vivax compared to chloroquine or AL 1

Important caveat: Both AL and DP prolong QTc interval and should be avoided in patients at risk for QTc prolongation or taking QTc-prolonging medications 2, 3

Severe Malaria - Medical Emergency

Severe malaria is defined by any of the following criteria 1:

• Parasitemia >2-5% (threshold varies by guideline and patient immunity status) 1
• Impaired consciousness or multiple seizures (>2 in 24 hours) 1
• Severe anemia (hemoglobin <7 g/dL with parasitemia >10,000/mL) 1
• Acute kidney injury (creatinine >3 mg/dL or urine output <400 mL/24h) 1
• Pulmonary edema, shock, hypoglycemia (<40 mg/dL), or acidosis 1

Treatment protocol for severe malaria:

• Intravenous artesunate: 2.4 mg/kg IV at 0,12, and 24 hours, then daily 1, 2

  • First-line treatment recommended by WHO, FDA-approved 2020, EMA-approved 2021 1
  • Superior to quinine with faster parasite clearance and shorter ICU stay 1

• Transition to oral therapy: Once parasitemia <1% and patient can tolerate oral medications, complete treatment with full course of oral ACT 1, 2

• Monitor for post-artesunate delayed hemolysis (PADH): Check hemoglobin on days 7,14,21, and 28 after treatment 2, 3

If artesunate unavailable, use intravenous quinine dihydrochloride: 20 mg salt/kg loading dose over 4 hours, then 10 mg/kg over 4 hours every 8 hours starting 8 hours after loading dose 1

• Inferior to artesunate for preventing red blood cell sequestration 1
• Monitor for QT prolongation and hypoglycemia 1

P. vivax, P. ovale, and P. malariae Treatment

Initial blood-stage treatment:

• Chloroquine-sensitive regions: Chloroquine 600 mg base, then 600 mg at 24 hours, then 300 mg at 48 hours (total 25 mg base/kg over 3 days) 1, 2, 4

  • First-line for P. vivax, P. ovale, P. malariae in chloroquine-sensitive areas 2

• Chloroquine-resistant regions (Papua New Guinea, Indonesia, Sabah): Use ACT, preferably dihydroartemisinin-piperaquine due to longer partner drug half-life 1

Radical cure for P. vivax and P. ovale (to eliminate liver hypnozoites and prevent relapse):

• Primaquine: 30 mg base daily for 14 days 1, 2

  • Mandatory G6PD testing before administration 1, 2
  • For mild-moderate G6PD deficiency (30-70% activity, A- variant): 45 mg weekly for 8 weeks with close monitoring 1
  • Contraindicated in pregnancy and breastfeeding 1
  • Reduces relapse risk by 80% 1

• Tafenoquine: Alternative single-dose option (not available in Europe) 1

  • Requires quantitative G6PD testing (do not use if <70% activity) 1
  • Contraindicated in pregnancy 1

Special Populations

Pregnant women:

• Artemether-lumefantrine can be used in all trimesters 2, 3
• Quinine plus clindamycin is alternative in first trimester when ACTs unavailable 3
• Never use primaquine or tafenoquine during pregnancy 1

Critical Pitfalls to Avoid

• Delayed diagnosis and treatment significantly increases mortality - treat immediately upon diagnosis 2, 3
• Underestimating parasitemia levels - different guidelines use thresholds between 2-5% for severe malaria; when in doubt, treat as severe 1, 2
• Inadequate fat intake with artemether-lumefantrine - this is the most common cause of treatment failure with AL 2, 3, 4
• Failing to test G6PD before primaquine/tafenoquine - can cause life-threatening hemolysis 1, 2
• Not monitoring for delayed hemolysis after artesunate - PADH can occur weeks after treatment 2, 3
• Using quinine or chloroquine in areas with known resistance - P. falciparum is chloroquine-resistant in most of Africa and Southeast Asia 5