What is the recommended treatment for complicated malaria?

Treatment of Complicated Malaria

Intravenous artesunate is the first-line treatment for complicated malaria and should be administered immediately at a dose of 2.4 mg/kg at 0,12, and 24 hours, then daily until the patient can take oral medication. 1

First-Line Treatment

• IV artesunate should be administered as a medical emergency in all patients with complicated malaria, as it provides faster parasite clearance and shorter ICU stays compared to quinine 1
• Dosing regimen: 2.4 mg/kg body weight at 0,12, and 24 hours, then daily until oral medication can be taken 1
• Continue IV artesunate until patient can tolerate oral medication and parasite density has decreased to <1% 1
• After parenteral therapy, patients should be switched to a complete course of oral artemisinin-based combination therapy (ACT) once they are clinically improved 1
• Preferred oral options include dihydroartemisinin-piperaquine or artemether-lumefantrine 1

Alternative Treatment (Second-Line)

• If intravenous artesunate is unavailable, intravenous quinine dihydrochloride can be used as a second-line option 2, 1
• Quinine dosing: 20 mg salt/kg loading dose over 4 hours, followed by 10 mg/kg over 4 hours starting 8 hours after initiation, and then every 8 hours 2
• Switch to oral therapy as soon as feasible, but not before completing 48 hours of IV treatment 2
• Monitor for adverse effects of quinine including QT prolongation and hypoglycemia 2

Monitoring During Treatment

• Parasitemia should be monitored every 12 hours until it declines to <1%, then every 24 hours until negative 1
• Most patients reach ≤1% parasitemia by the third artesunate dose with a median time of 17.6 hours 3
• Continuous monitoring of cardiocirculatory, pulmonary, kidney, and metabolic parameters is essential 1
• Monitor glycemia, plasma bicarbonate, and lactate levels 1
• Post-artesunate delayed hemolysis (PADH) should be monitored by checking hemoglobin, haptoglobin, and lactate dehydrogenase levels at days 7,14,21, and 28 1, 4

Special Considerations

• Artesunate can be used in all trimesters of pregnancy for severe malaria, as the benefits outweigh potential risks 4
• For patients with G6PD deficiency, artesunate is not contraindicated but requires careful monitoring for hemolysis 4
• Use artesunate with caution in patients with a significant risk of QT interval prolongation 4
• For patients from Southeast Asia, especially the Greater Mekong sub-region, with high levels of resistance to artemisinin-based therapies, alternative treatments should be considered 4

Supportive Management

• Restrictive fluid management should be used to avoid pulmonary or cerebral edema 1
• Acetaminophen may have reno-protective effects in patients with acute kidney injury (1g every 6 hours for 72 hours) 1
• Antibiotics should be started in cases of suspected bacterial co-infection but continued only if blood cultures are positive 1
• Exchange blood transfusion is not recommended as it has not been shown to improve outcomes 1

Effectiveness and Safety

• Mortality rate with appropriate treatment is approximately 1.8-3.6% in non-endemic settings 3, 5
• Adverse events associated with IV artesunate occur in approximately 4.8% of patients 3
• Post-artesunate delayed hemolysis occurs in approximately 37.4% of patients but typically resolves without intervention 4, 3

The evidence strongly supports IV artesunate as the treatment of choice for complicated malaria, with quinine as a second-line option when artesunate is unavailable. Early diagnosis and prompt treatment are critical for reducing mortality in complicated malaria cases.