What is the treatment for complicated malaria?

Treatment of Complicated Malaria

Intravenous artesunate is the first-line treatment for complicated malaria, administered at 2.4 mg/kg as a bolus at 0,12, and 24 hours, followed by daily dosing until the patient can transition to oral therapy. 1, 2

Initial Management of Complicated Malaria

First-Line Treatment

• IV Artesunate: 2.4 mg/kg at 0,12, and 24 hours, then daily
  • FDA approved in 2020, EMA approved in 2021 1
  • Demonstrated faster parasite clearance time and shorter ICU stays compared to quinine 1
  • Transition to oral therapy when:
    • Patient is clinically improved
    • Parasitemia is <1%
    • Patient can tolerate oral medication

Supportive Care

• ICU admission for continuous monitoring of:
  • Cardiocirculatory parameters
  • Pulmonary function
  • Renal function
  • Metabolic parameters (glycemia, plasma bicarbonate, lactate)
• Fluid management: Restrictive approach to avoid pulmonary or cerebral edema 1
• Acetaminophen: 1g every 6 hours for 72 hours may have renoprotective effects in acute kidney injury 1
• Antibiotics: Only if bacterial co-infection is suspected; discontinue if blood cultures are negative 1

Monitoring During Treatment

Parasitemia Monitoring

• Every 12 hours after starting treatment until parasitemia declines to <1%
• Then every 24 hours until negative 1
• Note: Parasite density may increase in first 24 hours with quinine therapy (not treatment failure)

Laboratory Monitoring

• For patients treated with IV artesunate, monitor for post-artesunate delayed hemolysis (PADH):
  • Hemoglobin, haptoglobin, and lactate dehydrogenase levels at days 7,14,21, and 28 1
• Daily monitoring of:
  • Complete blood count
  • Renal function
  • Liver function
  • Blood gas analysis

Transition to Oral Therapy

After 3 doses of IV artesunate and when parasitemia is <1%, transition to a full course of one of the available artemisinin-based combination therapies (ACTs) 1:

• Artemether-lumefantrine
• Dihydroartemisinin-piperaquine
• Artesunate-amodiaquine
• Artesunate-mefloquine

Important Considerations and Pitfalls

Contraindications and Cautions

• Mefloquine: Should not be administered with quinine or quinidine due to risk of electrocardiographic abnormalities 3
• Exchange blood transfusion: Not recommended with the availability of artesunate 1

Common Complications to Monitor

• Delayed hemolysis: Self-limiting episodes of unexplained hemolysis may occur after reduction of parasitemia levels 4
• Hypoglycemia: Common complication requiring frequent monitoring
• Acute kidney injury: Monitor urine output and creatinine
• Pulmonary edema/ARDS: Requires careful fluid management
• Cerebral malaria: Monitor neurological status closely

Special Populations

• Patients on hydroxyurea: Artesunate can be safely administered with hydroxyurea as there are no documented contraindications 2
• Plasmodium knowlesi infections: Intravenous artesunate is highly effective for severe disease and those with moderately high parasitemia 5

Follow-up After Treatment

• Continue monitoring until complete parasite clearance
• For patients treated with IV artesunate, follow up at days 7,14,21, and 28 to monitor for delayed hemolysis
• Educate patients from areas with resistant parasites about the possibility of recurrent infection and the need for immediate medical attention if symptoms return 1

Complicated malaria is a medical emergency requiring prompt diagnosis and treatment. The rapid initiation of IV artesunate, appropriate supportive care, and careful monitoring are essential to reduce mortality and improve outcomes.