Treatment of Severe Malaria
Intravenous artesunate is the first-line treatment for severe malaria and should be administered immediately as a medical emergency. 1, 2
Diagnosis of Severe Malaria
Severe malaria is characterized by:
- Impaired consciousness, confusion, or coma 2, 1
- Multiple convulsions or seizures 1
- Severe anemia, thrombocytopenia 2, 1
- Hypotension and respiratory distress 2, 1
- Jaundice and elevated bilirubin 2
- Acute kidney injury (oliguria, anuria, elevated creatinine) 2, 1
- Metabolic acidosis with hyperlactatemia 2, 1
- Hypoglycemia 2, 1
- High parasitemia (>2%) 2, 3
First-Line Treatment
- Intravenous artesunate at 2.4 mg/kg body weight at 0,12, and 24 hours (3 doses), then daily until oral medication can be tolerated 2, 1
- This regimen has been shown to provide faster parasite clearance and shorter ICU stays compared to quinine 2, 3
- FDA approved artesunate in 2020, with EMA approval following in 2021 2
- Parasite clearance time to 50% reduction averages 4.4 hours, with 90% clearance at 14.8 hours and 99% clearance at 29.5 hours 4
Transition to Oral Therapy
- Once the patient is clinically improved (parasitemia <1%) and able to take oral medication, switch to a complete course of oral artemisinin-based combination therapy (ACT) 2
- The full course of the chosen ACT must be administered to ensure complete parasite clearance 2
Supportive Management
- Admit to intensive care unit for continuous monitoring 2, 1
- Use restrictive fluid management to avoid pulmonary or cerebral edema 2, 1
- Consider acetaminophen (1g every 6 hours for 72 hours) for potential reno-protective effects in patients with acute kidney injury 2, 1
- Start antibiotics if bacterial co-infection is suspected; continue only if blood cultures are positive 2, 1
- Exchange blood transfusion is not recommended as it has not been shown to improve outcomes 2
- Manage hypoglycemia with glucose supplementation 2, 1
- Treat seizures with appropriate anticonvulsants 2
Monitoring During Treatment
- Check parasitemia every 12 hours until it declines to <1%, then every 24 hours until negative 2, 1
- Monitor complete blood count, liver function, kidney function, and metabolic parameters daily 2, 1
- Perform blood gas analysis to monitor acidosis and lactate levels 2, 1
- Watch for post-artesunate delayed hemolysis (PADH) by checking hemoglobin, haptoglobin, and LDH on days 7,14,21, and 28 after treatment 2, 1
Alternative Treatment Options
- If intravenous artesunate is unavailable, intravenous quinine is the alternative 5
- For patients unable to swallow who are awaiting hospital transfer, intramuscular quinine (10 mg/kg) can be administered 2
Special Considerations
- Artesunate can be used in all trimesters of pregnancy for severe malaria 5
- Use with caution in patients with G6PD deficiency due to risk of post-artesunate delayed hemolysis 5
- Monitor for QT interval prolongation in susceptible patients 5
- In regions with artemisinin resistance (Greater Mekong subregion), alternative treatments may be needed 5, 6
Common Pitfalls and Caveats
- Delayed treatment is associated with increased mortality - severe malaria requires immediate intervention 3, 7
- Post-artesunate delayed hemolysis occurs in approximately 37% of patients treated with artesunate 5, 4
- Higher parasite densities (>10%) are associated with longer parasite clearance times 7
- Mortality remains approximately 1.8-3.6% even with appropriate treatment 4, 7
- Do not continue intravenous therapy longer than necessary - transition to oral therapy once the patient improves 4